Honoring the Past, Shaping the Future. 75 YEARS OF DISCOVERY, INNOVATION AND CARE
Division of Gastroenterology and Hepatology
UNIVERSITY OF MICHIGAN HEALTH SYSTEM Acknowledgements
I would like to express my sincere gratitude to every person whose hard work and dedication to the Division has made our 75 year journey truly remarkable. Our Division today is fortunate to be enriched not only by our faculty, fellows and investigators, but by over 150 talented staff. Every individual’s contribution is invaluable and very much appreciated. Following the 75 th Anniversary Theresa Nester, Administrative Hilary Robinson, Associate Director, Celebration I received many heartfelt Specialist, Division of Michigan Creative, and the Michigan messages from guests letting me Gastroenterology and Hepatology Creative team including, Martin know how much they enjoyed Soave and Ruth Gretzinger, Lori Hirshman, Associate Director themselves at the events. I would like and also Kim Roth, from Outword of Development, Marie Marsneck, to thank the following individuals Communications Development Assistant, and Jane for their tireless efforts to ensure the Bronson, Development Events Team Sincerely, celebration was an overwhelming success. Bill Burgard, Lecturer II, Stamps School of Art and Design Jeff Holden, MBA, Division Administrator, Division of CHUNG OWYANG, MD, Gastroenterology and Hepatology Chief, Division of Gastroenterology and Hepatology
© 2016 Regents of the University of Michigan Table of Contents
Welcome...... 3
Foundations: Our History ...... 5
Committed to Excellence...... 27
Faculty Leadership...... 28
Clinical Programs ...... 41
Education + Training ...... 88 1 Basic, Clinical + Translational Research...... 102
Global Reach: Engaging with the World...... 143
Recognition + Awards: Honoring the Leaders and Best. . . 149
Friends + Donors ...... 155
Poised for Growth ...... 163
Celebrate!...... 169
Thank You...... 184
Acknowledgments 2 Welcome
The world was a different place 75 As you read through these pages, We’ve done great work, and we’ve years ago, when the nascent Division you’ll find the history of our Division had fun doing it. As one former of Gastroenterology and Hepatology in words and images. From the faculty member put it, “There are began. A new car cost $850, and gas earliest days of the first Division very few academic departments in was 12 cents a gallon. Thanksgiving Chief H. Marvin Pollard, who any university in the world with this had just become an official national introduced the fiberoptic endoscope, much talent, and faculty who stay in holiday. The Maltese Falcon was one to this year’s brand-new innovations harmony and love and respect each of the most popular movies and in research and clinical care, the other.” “Chattanooga Choo-Choo” one of the Division has remained true to its Here’s to the next 75 years of research most popular songs. And the massive mission of finding new solutions and discovery! presidential sculptures on Mount for clinical issues and developing 3 Rushmore were unveiled. and training the next generation of leaders. But while much has changed, some things remain constant, including our commitment to excellence in CHUNG OWYANG, MD patient care. 4 Foundations: OUR HISTORY 5 6
BASIL I. HIRSCHOWITZ, MD 7
R.J. BOLT, MD
ARTHUR B. FRENCH, MD
Dr. H. Marvin Pollard { Division Chief 1947 – 1972 } The Pollard Era { 1940 – 1972 }
Under the leadership of DR. H. MARVIN POLLARD (MD 1931, Residency 1933), the University of focused on gastrointestinal peptides, Michigan Division of Gastroenterology was founded in the 1940s, long before the specialty the Pollard GI Research Institute was officially recognized by the American Board of Internal Medicine. Dr. Pollard attended a helped demonstrate the Division’s number of postgraduate courses, but he was not formally trained as a gastroenterologist . long history of and commitment to Still, he went on to become a renowned pancreatic cancer researcher, a visionary leader successful clinical and translational of the Division and an innovative thinker . With characteristic foresight, he laid a strong research. A grant to establish the new foundation upon which the Division would continue to grow and flourish in clinical care, center was awarded, and the Center for training and research . Gastrointestinal Research is thriving and has been continuously funded Dr. Pollard was the first to no resources available at that time first of its kind to receive National since its founding in 1984. introduce the fiberoptic to fund such programs, Dr. Pollard Institutes of Health research funding 8 endoscope, a semi-rigid undertook a fundraising effort, and career development awards. It During his tenure, Dr. Pollard trained a endoscope, into the GI personally soliciting donors. He used remains in existence today and has number of notable gastroenterologists, Division’s clinics. He the monies to help establish the first played a significant role in many who went on to become prominent believed strongly in the gastrointestinal research unit at the investigational efforts over the years inventors, clinicians and leaders importance of research to University of Michigan. as well as in attracting TADATAKA in their own right: DRS. BASIL I. fuel innovation in clinical “TACHI” YAMADA, MD, KBE, to the HIRSCHOWITZ KEITH S. HENLEY A foundation for research , , practice and that every University as Division Chief in 1983. ROBERT J. BOLT WILLIAM H. excellence , prominent academic entity BACHRACH, ARTHUR B. FRENCH, When Dr. Yamada and DR. CHUNG should devote considerable time The resulting Marvin Pollard GI LUDOVIC STANDAERT, JORGE OWYANG, current Division Chief, and effort in pursuit of basic and Research Center represented a GUMUCIO, MILTON WEISER and applied to the NIH in the early 1980s to clinical research. Since there were groundbreaking institution, the DAVID W. WATSON. support an additional research center Invention and innovation Julius Friedenwald Medal, the highest An inspiring mentor to his U-M distinction bestowed by the American colleagues and a masterful clinician One of the most important Gastroenterological Association. with patients, Dr. Pollard also President of AGA, ASGE, ACP, developments during the Pollard generously gave of his time to the American Cancer Society era was Dr. Hirschowitz’s invention An equally important achievement profession. He presided over a of the fiberoptic endoscope, the first during the Pollard era was the number of organizations including the fully flexible scope able to examine development of a simplified multiple- American Gastroenterology Association, the upper gut. Working together retrieving small-bowel biopsy tube. In the American College of Physicians and 1st with renowned fiberoptics experts 1962, Drs. Bolt and French, who both the American Cancer Society. He was Drs. Hopkins and Kapany, and trained under Dr. Pollard, performed Founder and first Division also one of the founders of the World subsequently with U-M colleagues the modern era’s first intestinal biopsy. Chief of Gastroenterology Gastroenterology Organisation and C. Wilbur Peters and undergraduate The three physicians published their (1940 – 1972) 9 served as its president. student Lawrence E. Curtiss of the invention and findings in The American Physics department, Dr. Hirschowitz Journal of Digestive Diseases (1962; The endowments in Dr. Pollard’s name completed construction of the first 7: 773). have grown over the last 30 years and 1st generation fiberscope, supported with currently fully support seven endowed Using this instrument, Drs. French resources provided by Dr. Pollard. professorships within the Division of Development of first fiberoptic and Bolt performed pioneering The invention became the prototype Gastroenterology. Dr. Pollard retired in gastroscope studies correlating morphology and for the gastroduodenal scope the 1972, after more than three decades malabsorption in celiac disease. Division now uses in its Medical leading the Division. Renowned researcher in Subsequently, Dr. French went on to Procedures Unit. For this achievement, pancreatic cancer serve as the first director of the U-M Dr. Hirschowitz was awarded the Clinical Research Unit. JORGE J. GUMUCIO, MD
10 MILTON G. MUTCHNICK, MD 11
WILLIAM O. DOBBINS III, MD
STANLEY R. STRASIUS, MD
Dr. Keith S. Henley { Division Chief 1972 – 1981 } The Henley Era { 1972 – 1981 }
After Dr. Pollard retired in the fall of 1972, DR. KEITH S. HENLEY, a hepatologist interested in alcoholic liver disease, was appointed the second Chief of Gastroenterology . Dr . Henley quickly became known for his integrity, accessibility, scrupulous fairness and deep moral conscience . Financial pressures in the late Dr. Henley was able to attract become the U-M Liver Transplant 1960s challenged Dr. Henley budding Gl talent, including Program, one of the first in the to continue to build a current Division Chief DR. United States. The results of his community of of scholars CHUNG OWYANG; DR. TIMOTHY clinical efforts and his hepatology in gastroenterology once T. NOSTRANT; DR. JOEL V. research have had far-reaching he took over as chief. He WEINSTOCK and DR. JEANPIERRE impact on the care of liver disease devoted considerable RAUFMAN, both of whom are now and liver transplant patients. 12 effort to recruiting faculty division chiefs at other institutions; Dr. Henley led the Division until capable of obtaining NIH DR. JOHN A. SCHAFFNER, who 1981 and retired in 1993. grants in order to help enjoys a distinguished career as an rejuvenate the Division. educator at the Mayo Clinic; and DR. STANLEY R. STRASIUS, who is a Together with DRS. leading teacher at St. Joseph Mercy MILTON G. MUTCHNICK Hospital in Ann Arbor. and JORGE GUMUCIO, Dr. Henley developed a research Dr. Henley also strengthened the GI group dedicated to the study of basic presence at the Ann Arbor VA hospital and translational hepatology. and helped develop what would 13
Dr . Chung Owyang with Dr . Henley (1979) JOANNE WILSON, MD
14
DR. NOSTRANT WITH DR. WILLIAM D. CHEY 15
Dr. Timothy T. Nostrant { Division Chief 1981 – 1983 } The Nostrant Era { 1981 – 1983 }
In 1981, DR. TIMOTHY T. NOSTRANT, then an assistant professor who had completed his GI fellowship training at the University of Michigan, was appointed acting chief following Dr . Henley . At the time, the nature of System (UMHS), with over 30,000 Nostrant built this unit into one of gastroenterology was changing procedures performed in 2016 alone. the most productive and sought- with the advancements after consultative services in the Dr. Nostrant made significant brought by endoscopy Department. Its multi-subspecialty contributions to the field of technology. Dr. Nostrant approach to consultation has served esophageal motility disorders and recognized the importance as a blueprint for other departments trained many of the key clinical and potential of across the UMHS. faculty members in the Division. He endoscopy, and he developed the core curriculum for the 16 was instrumental in Gastroenterology Fellowship Program, establishing one of the much of which is still in use today. world’s most sophisticated and well-equipped Dr. Nostrant also served as the medical procedures units lead physician of the Department (MPU) to expand the use of internal Medicine’s Faculty of the technology. To this Diagnostic Unit, which was day, the MPU that Dr. Nostrant designed to be a national model helped create remains one of the for the development of the clinician most successful clinical units in scholar track of academic medicine. the University of Michigan Health Within a relatively short time, Dr. 17 18
RICHARD H. MOSLEY, MD JOHN DEL VALLE, MD C. RICHARD BOLAND, MD REBECCA W. VAN DYKE, MD MICHAEL R. LUCEY, MD PAUL WATKINS, MD
19
Dr. Tadataka “Tachi” Yamada { Division Chief 1983 – 1990 } The Yamada Era { 1983 – 1990 }
In 1983, DR. TADATAKA “TACHI” YAMADA joined the University of Michigan as Chief of of nearly 50 percent of all known Gastroenterology—selected for his unique potential, vision and drive, despite the fact that he peptide hormones. Many of Dr. was a relatively young researcher at the time . Yamada’s observations have clinical implications as fundamental tools When Dr. Yamada assumed the The Center provided the infrastructure of these hormones. His first major for understanding the pharmacology role of Division Chief, the for Dr. Yamada to build one of the breakthrough was the development of histamine receptor antagonists Division had just seven full- strongest Gl research programs in the of an isolated cell system to study the and serve as the basis of important time faculty members and a country, and it played a key role in the regulation of peptide secretion from pharmacological interventions for single NIH research grant. recruitment of DR. JOHN WILLIAMS gastrointestinal endocrine cells. Until health problems such as obesity. Dr. Yamada saw this as a to the Division as well as DR. BISHR the introduction of this technology, it tremendous opportunity. OMARY to the Chair of Physiology was virtually impossible to study the As Chief, Dr. Yamada had a gift for 20 His first major initiative and DR. JACK DIXON to the Chair of cell biology of gut hormones because bringing scientists from different was to write a highly multi- Biological Chemistry. they are contained in cells dispersed backgrounds together and fostering disciplinary—and winning— throughout the mucosa, rather than deep collaborations in pursuit of Dr. Yamada was a true pioneer in gut proposal for a National isolated within endocrine glands. groundbreaking research. He recruited endocrinology. He was among the earli- Institutes of Health Digestive a number of promising young est investigators to apply molecular Another equally important Diseases Center grant, which physician-scientists to the Division. biology techniques to the study of contribution was the isolation and was crucial in establishing the These include DRS. RICHARD biochemistry and physiology of gut characterization of glycine-extended University of Michigan Center for BOLAND, RICHARD MOSELEY, hormones. He made a number of novel processing intermediates of gastrin, Gastrointestinal Research, the first PAUL WATKINS and REBECCA VAN contributions vital to our understand- which provided tools of critical center in the United States dedicated to DYKE. ing of the synthesis, release and actions importance in the biological activation the investigation of gut peptides. Dr. Boland served as Section Chief of Dr. Yamada is also known for helping Medicine and MED-Peds Residency Many foreign fellows mentored by Dr. the VA Ann Arbor Healthcare System junior faculty launch their careers and Programs at U-M. DR. GRACE ELTA, Yamada also have gone on to achieve and, subsequently, as Division Chief realize their potential. Many of the H. Marvin Pollard Collegiate Professor significant academic success. Dr. at University of California, San Diego. faculty members he trained have gone of Gastroenterology, directs the U-M Kentaro Sugano is Chair of Medicine at Dr. Moseley succeeded Dr. Boland as on to become academic leaders in Medical Procedures Unit. She was the Jichi University, and Dr. Tsutomo Chiba VA Section Chief and subsequently gastroenterology and hepatology. DR. first woman to serve on the governing is Chair of Medicine at Kyoto University, was appointed Chief of Medicine of PETER TRABER became Chair of the board of the American Gastroentero- both in Japan. the VA Ann Arbor Healthcare System. Department of Internal Medicine and logical Association and served as the During Dr. Yamada’s tenure, annual Dr. Watkins is a renowned expert subsequent Dean of Medicine at the first female president of the American research funding increased from about in liver drug toxicity and served as University of Pennsylvania, and also Society for Gastrointestinal Endos- $200,000 to $4 million, setting the director of the clinical research center served as president of Baylor College copy. DR. JUANITA MERCHANT, stage for the $15 million in funding the 21 at U-M. He now directs the Hamner- of Medicine. endowed Professor of Medicine, directs Division generated in 2016. University of North Carolina Institute a thriving, internationally renowned DR. CHRIS DICKINSON has served as for Drug Safety Sciences. Dr. Van Dyke research program on transcriptional Another major achievement for Dr. Chief of Pediatric Gastroenterology at became Professor of Medicine at control mechanisms in the gastrointes- Yamada was editing the Textbook of U-M for many years and is now Chief U-M, contributing significantly to the tinal tract. DR. JAMES SCHEIMAN is Gastroenterology, one of the most-used Clinical Officer of the C.S. Mott Chil- Division’s medical education mission Professor of Medicine and directs the GI textbooks to date. It is considered a dren’s Hospital and the Von Voigtlander and earning many awards for her Advanced Endoscopy Fellowship pro- standard GI textbook both in the U.S. Editors of Textbook of Gastroenterology: Women’s Hospital. DR. JOHN DEL teaching and mentorship. She was gram at U-M. DR. MICHAEL LUCEY, and worldwide. It is currently in its 6th Don W . Powell, Chung Owyang, Tadataka Yamada, VALLE, a former Robert Wood Johnson named professor emerita in 2014. an expert in liver transplant, serves as edition. Fred E. Silverstein, David H. Alpers trainee, now serves as Associate Chief of Gastroenterology and Hepatol- Chair of Medicine and Director of the ogy at the University of Wisconsin. JOSEPH C. HARI KOLARS, MD WILLIAM L. FRED ASKARI, MD, CONJEEVARAM, HASLER, MD PhD MD, MSc
22 JOHN M. JUANITA L. CARETHERS, MD MERCHANT, MD, PhD
GRACE SU, MD JAMES M. PETER D.R. GRACE ELTA, MD LESLIE B. SCHEIMAN, MD JOHN W. WILEY, HIGGINS, MD, PhD, ALDRICH, MD MD MSc ANNA SUK-FONG ROBERT J. WILLIAM D. CHEY, M. BISHR OMARY LOK, MD, FRCP FONTANA, MD MD MD, PhD
JOHN R. SPENCE, PhD 23
ELIZABETH K. SPELIOTES, MD, PhD, MPH
THOMAS D. WANG, MD, PhD PHILIP S. SCHOENFELD, MD, JOHN M. MSED, MSc INADOMI, MD
Dr. Chung Owyang { Division Chief 1990 – Present } The Owyang Era { 1990 – Present }
In 1990, DR. TACHI YAMADA became Chair of Internal Medicine and DR. CHUNG OWYANG was JOHN WILEY (visceral hypersensitivity appointed Chief of Gastroenterology and Hepatology . Dr . Owyang brought his energy and and IBS), WILLIAM D. CHEY (food vision to strengthen the Division’s accomplishments . allergy and IBS), WILLIAM HASLER (gastroparesis), Philip Schoenfeld Like Dr. Yamada, Dr. Owyang is nervous system and was the first HARI CONJEEVARAM, leading expert (outcomes research and functional also a gut endocrinologist. His to propose the use of somatostatin in non-alcoholic fatty liver disease bowel disorders), RICHARD SAAD work focuses on the neuronal in the treatment of intestinal and Director of the Gastroenterolgy (pelvic floor disorders and colonic hormone control of digestive pseudoobstruction. His research work and Hepatology Fellowship Training inertia), SHANTI ESWARAN (IBS) functions in pancreatic has been continuosly funded by the Program; DR. FRED ASKARI, Director and JOEL RUBENSTEIN (esophageal exocrine secretion and NIH over the last 30 years. of the nationally recognized Center of motility disorders, reflux and Barrett’s GI motility. One of his Excellence in Wilson Disease; and DR. As Division Chief, one of Dr. Owyang’s Esophagus). Dr. Owyang’s own research 24 major achievements GRACE SU, Chief of Gastroenterology first initiatives was to establish a has focused on intestinal pseudo- is the characterization at the VA Ann Arbor Healthcare System. clinical hepatology unit, recruiting obstruction, microbiome and IBS. of a trypsin-sensitive DR. ANNA LOK, an expert in viral Dr. Owyang also fortified the Division’s CCK-releasing factor, In 2000, Dr. Owyang oversaw the hepatitis, as its director. Under her strength in health services research, which is secreted in the transformation of the Michigan Gas- leadership, the Division groomed many recruiting DRS. PHILIP SCHOENFELD intestinal lumen following trointestinal Peptide Research Center leading hepatologists, including DR. and JOHN INADOMI, who helped feeding. This novel observation into the University of Michigan Center ROBERT J. FONTANA, Director of the the Division secure highly competitive has provided the basis for for Gastrointestinal Research. More University of Michigan Liver Transplant NIH T32 training grants in clinical understanding the clinical utility of than 75 faculty from Gastroenterology Program and Transplant Hepatology epidemiology and outcomes research. pancreatic enzyme supplements in and Hepatology, Physiology, Cell Biol- Fellowship Program; DR. JORGE alleviating pain in chronic pancreatitis. Dr. Owyang established one of the ogy, Microbiology, Pharmacology and MARRERO, leader of our nationally Dr. Owyang also studied the in vitro country’s most comprehensive motility Surgery galvanized the efforts of the designated liver cancer program; DR. action of somatostatin on the enteric disorder groups, which includes DRS. established group of gut peptide in- vestigators. The Center is now a pillar human population-based studies and director of the Gl Physiology Laboratory. Division’s clinical services encompass bestowed the Julius Friedenwald of the Division, promoting academic functional genomics to determine DR. ELLEN ZIMMERMAN went on to 14 locations and four endoscopy Medal, its highest honor, upon Dr. development and fueling recruiting the genetics of obesity and fatty serve as associate chair of medicine at centers across Michigan. As of Owyang for his lifelong contributions to efforts for the Division and across the liver disease. DR. JASON SPENCE, the University of Florida and DR. URI 2016, the Division had over 41,000 the field of gastroenterology. In the last Department of Internal Medicine. a developmental biologist, creates LADABAUM serves as acting chief of outpatient clinic visits and performed 50 years, two of our Division Chiefs— three-dimensional organoid models gastroenterology at Stanford University. more than 30,000 procedures. DRS. YAMADA and OWYANG—have With Center support, several key to study intestinal stem cells. DR. been awarded this honor. DRS. NIH-funded research programs During his tenure, Dr. Owyang has With nearly $15 million of NIH funding PETER HIGGINS, who directs TIMOTHY NOSTRANT, GRACE ELTA, were developed. Collaborating greatly expanded the Division’s each year, Division scientists and our inflammatory bowel disease and WILLIAM D. CHEY have received with DRS. DEBORAH GUMUCIO, clinical services and outreach clinicians work side by side to provide program, established the Division’s the AGA Distinguished Clinician Award. LINDA SAMUELSON and ANDREA programs. By 2016, with a clinical the most advanced and innovative Biospecimen Banking Service to The AGA Distinguished Educator Award TODISCO, DR. JUANITA MERCHANT practice involving more than 75 treatment options and care. Our 25 facilitate the translation of basic was given to DRS. JOHN DEL VALLE initiated a novel program to study full-time faculty, the Division became Digestive and Liver Health Center discoveries in cell lines and mouse and JOSEPH KOLARS. DR. ANNA cellular decisions of differentiation in the second largest digestive and liver is now a preferred referral center models to human applications. LOK has received several awards for the Gl tract, showing that Hedgehog health group in the nation. throughout Michigan and the world. her work, including the prestigious pathology mediates the transition from The Division continues to train the next The Division has housed The American Under the leadership of DR. GRACE AGA William Beaumont Prize in inflammation to cancer in the Gl tract. generation of physicians. Many gradu- Journal of Gastroenterology and ELTA, the Medical Procedures Unit Gastroenterology in 2016. These ates of our Gl Fellowship Training Pro- Gastroenterology, with DRS. BISHR The Center also was instrumental in has become a hub for all major awards represent only a fraction of the gram have become academic leaders in OMARY and WILLIAM D. CHEY, recruiting DR. THOMAS WANG, a endoscopy procedures. A second enormous accomplishments of our their own right. Notables include U-M respectively, serving as editors-in-chief. physician scientist and biomedical Medical Procedure Center was opened faculty over the past 75 years. Chair of Internal Medicine DR. JOHN engineer whose molecular imaging in 2005 at the East Ann Arbor Health Many faculty have emerged as world CARETHERS; DR. JOSEPH KOLARS, techniques elucidate gene and Campus and, under the direction of leaders in gastroenterology and senior associate dean of medicine; and protein expression. Center investigator DR. LESLIE ALDRICH, has performed hepatology. In 2013, the American DR. WILLIAM D. CHEY, professor and DR. ELIZABETH SPELIOTES uses over 9,000 procedures in 2016. The Gastroenterology Association (AGA) 26 Committed to Excellence 27 28 Faculty Leadership FACULTY LEADERSHIP
Current Faculty Members
The faculty is the most valuable resource of the Division . Special emphasis is placed on faculty ROBERT JOHN FONTANA PETER DOYLE HIGGINS mentoring and career support . Each junior faculty (clinical lecturer and assistant professor) Professor Associate Professor member is assigned a mentorship committee which meets quarterly and a career plan and MERRITT G. GILLILLAND III SHUANGSONG HONG timeline are carefully mapped out. As a result, an 80 percent success rate was achieved in Research Investigator Assistant Research Scientist obtaining career development awards . LISA M. GLASS AMY HOSMER Lecturer Lecturer MEGAN ADKINS ADAMS JOHN M. CARETHERS JOHN DEL VALLE SHAIL GOVANI NOBUHIKO KAMADA Lecturer Professor Professor Lecturer Assistant Professor LESLIE BROWN ALDRICH CRISTINA CEBRIAN LIGERO MATTHEW J. DIMAGNO GINTAUTAS GRABAUSKAS JOHN Y. KAO Assistant Professor Lecturer Assistant Professor Assistant Research Scientist Associate Professor JOHN IRVIN ALLEN JOAN CHEN MOHAMAD EL ZAATARI 29 TANNAZ GUIVATCHIAN ALBERT C KIM Professor Lecturer Research Investigator Adjunct Lecturer Lecturer MICHELLE A. ANDERSON WILLIAM D. CHEY BADIH JOSEPH ELMUNZER DEBORAH L. GUMUCIO JAMI KINNUCAN Associate Professor Professor Adjunct Assistant Professor * Professor Lecturer FREDERICK K. ASKARI HARI S. CONJEEVARAM GRACE H. ELTA WILLIAM LEE HASLER MINORU KOI Associate Professor Professor Professor Professor Associate Research Scientist ALLAN BARBISH HOWARD C. CRAWFORD * SHANTI L. ESWARAN TADD HIATT JOSEPH C. KOLARS Instructor Professor Assistant Professor Lecturer Professor SHRINIVAS BISHU DUYEN DANG LAUREL R FISHER Assistant Professor Associate Professor Associate Professor Emeritus
* Joint Appointment MONICA A. T. KONERMAN COSTAS ANDREAS LYSSIOTIS * BISHR OMARY * MEGAN ELIZABETH RIEHL YATRIK M. SHAH * Lecturer Assistant Professor Professor Instructor Associate Professor JACOB E. KURLANDER JOHN C. MAGEE * CHUNG OWYANG RAF S. RIZK PRATIMA SHARMA Lecturer Professor Professor Assistant Professor Assistant Professor HELLAN KANG KWON BETH ROSE MANOOGIAN AARTI OZA BEDI JOEL HOWARD RUBENSTEIN NEIL SHETH Assistant Professor Assistant Professor Lecturer Associate Professor Lecturer RICHARD S. KWON JESSICA MELLINGER NEEHAR PARIKH LIANGYOU RUI * DMITRY SHUSTER Assistant Professor Lecturer Lecturer Professor Lecturer RYAN J. LAW STACY B. MENEES ANOOP PRABHU RICHARD J. SAAD ELIZABETH SPELIOTES 30 Lecturer Assistant Professor Lecturer Associate Professor Associate Professor ALLEN LEE JUANITA L. MERCHANT DARASHANA PUNGLIA SAMEER D. SAINI JASON SPENCE Lecturer Professor Lecturer Assistant Professor Associate Professor HAIJUN LI RICHARD H. MOSELEY NATALIYA RAZUMILAVA LINDA C. SAMUELSON * RYAN WILLIAM STIDHAM Research Investigator Professor Emeritus Lecturer Professor Assistant Professor JI-YAO LI MICHELLE M. MUZA-MOONS ANDREW READ JAMES MICHAEL SCHEIMAN ELENA M. STOFFEL Assistant Research Scientist Lecturer Lecturer Professor Assistant Professor ANNA SUK-FONG LOK BORKO NOJKOV MICHAEL D. RICE PHILIP S. SCHOENFELD GRACE L. SU Professor Lecturer Instructor Adjunct Professor Professor
* Joint Appointment FACULTY LEADERSHIP
ANDREW W. TAI THOMAS D. WANG Instructional or Lecture Track Clinical Track Research Track Assistant Professor Professor Professor 16 Clinical Professor 2 Assistant Research Scientist 9 MIMI S. TAKAMI JOHN W. WILEY Assistant Professor Professor Associate Professor 6 Clinical Associate Professor 3 Research Investigator 6 JOHN ANDREW WILLIAMS * ELLIOT TAPPER Assistant Professor 12 Clinical Assistant Professor 10 Total: 15 Assistant Professor Professor TADATAKA YAMADA Clinical Lecturer 23 Clinical Instructor 3 ANDREA TODISCO Adjunct Professor Professor Total: 57 Total: 18 Luminal GI 60 JUAN ZHOU STEPHANIE S. TSENG-ROGENSKI Research Investigator Hepatology 15 Assistant Research Scientist SHI-YI ZHOU 31 Men 46 (61%) Subtotal: 75 DANIELLE KIM TURGEON Assistant Research Scientist Professor Women 29 (39%) MICHAEL VOLK Research Track 15 Adjunct Assistant Professor Joint Appointment 9 AKBAR WALJEE Assistant Professor Total: 99 ERIK-JAN WAMSTEKER Associate Professor Endowed Professorships: AN ENDURING LEGACY OF RESEARCH, CARE AND TRAINING
With the foresight and generosity of committed donors, the Division has established several poses in the late 1970s at the U-M. In endowed professorships . These chairs help to create an enduring legacy for the Division that 1982, biliary sphincterotomy for stone enables and sustains our highly innovative research, patient care and training for the next extraction was added. The use of ERCP generation of gastroenterologists . for treatment of pancreatic and biliary disorders has since grown tremen- The H. Marvin Pollard he touched the lives of thousands of 2006, distributions from the original dously and now includes pancreatic Professorships patients with his skill and compassion. fund created a third professorship: endotherapy and numerous biliary One of those patients was Shirley the H. Marvin Pollard Professorship A nationally renowned pancreatic can- tract treatments. These procedures McLaughlin, who died in 1987 and in Internal Medicine. In 2008, further cer researcher, Dr. Pollard was named significantly reduce the need for whose husband Robert was grateful for distributions funded the establishment head of the Section of Gastroenterolo- invasive surgeries. the care his wife had received at U-M. of the H. Marvin Pollard Professorship gy in 1940 and Chief of the Division of Grace Elta, MD, FASGE 32 Following Robert’s death in 1989, his in Gastrointestinal Sciences. In all, five Dr. Elta’s productive research program Gastroenterology in 1947. In 1956, Dr. estate authorized the creation of two professorships continue to honor Dr. Ambulatory Care Unit, and serves as focuses on biliary tract disease, Pollard secured funds to support Dr. professorships at U-M, including the H. Pollard’s indelible legacy of leadership, Associate Chief of Clinical Programs. An endoscopic ultrasound and pancreatic Basil I. Hirschowitz’ (Residency 1956) Marvin Pollard Professorship in Gastro- research, teaching and healing. experienced interventional endosco- disease. She is a nationally renowned development of the first flexible enterology, established in 1993. pist, Dr. Elta also heads the Pancreatic endoscopist who served as President fiberoptic gastroscope; Dr. Pollard GRACE ELTA, MD and Biliary Disorders Clinic, where she of the American Society for Gastroin- helped develop and refine the device, Two years later, a group of Dr. H. Marvin Pollard Collegiate performs endoscopic ultrasound and testinal Endoscopy (ASGE) in 2007 the prototype of which is now housed Pollard’s former colleagues, friends Professor of Gastroenterology therapeutic endoscopic retrograde chol- and the American Gastroenterological in the Smithsonian. and trainees joined forces to fund Dr. Grace Elta joined the Division faculty angiopancreatography (ERCP). Association (AGA) DDW Council Chair a second professorship bearing his Dr. Pollard retired in 1972. During in 1982. She directs the Medical Pro- beginning in 2013. She was inducted name: the H. Marvin Pollard Collegiate The specialized ERCP procedure was his long and dedicated U-M career, cedures Unit and the Taubman Clinic into the U-M Department of Internal Professorship in Gastroenterology. In first performed for diagnostic pur- FACULTY LEADERSHIP
Medicine Clinical Excellence Society ologies for in vivo imaging of the di- A popular teacher, Dr. Wang has cells in the stomach. Her laboratory in 2013 and installed as H. Marvin gestive tract for early cancer detection mentored junior faculty, postdoctoral also developed the first mouse model Pollard Collegiate Professor of Gastro- and staging. research fellows, clinical fellows, of gastric carcinoids. This in vivo model enterology in 2015. medical residents, medical students of a GI endocrine cancer will enable Dr. Wang has developed confocal and many graduate and undergraduate testing of new drug therapies. THOMAS D. WANG, MD, PhD and multiphoton endomicroscopy students from U-M and around the H. Marvin Pollard Collegiate platforms and the first video endoscope As associate director of the U-M Medical world. He was installed as H. Marvin Professor of Endoscopy Research sensitive to fluorescence for rapidly Scientist (MD-PhD) Training Program, Pollard Collegiate Professor of identifying pre-malignant lesions over Dr. Merchant developed a clinical Dr. Thomas Wang joined the Division Endoscopy Research in 2015. large mucosal surface areas. He has preceptorship for MSTP students and in 2007. The gifted physician scientist pioneered the use of fluorescence- JUANITA L. MERCHANT, MD, PhD a pre-MSTP summer program for works at the forefront of molecular Juanita Merchant, MD PhD labeled peptides to detect overex- H. Marvin Pollard Professor of undergraduate students from groups 33 imaging, developing novel method- pressed cell surface targets in vivo. Gastrointestinal Sciences Dr. Merchant’s laboratory demon- currently underrepresented in science strated that gastrin is regulated by and medicine. Dr. Merchant’s seminal Dr. Wang’s approach—combining An internationally renowned molec- inflammatory mediators, leading to the research contributions were recognized imaging information with biological ular gastroenterologist, Dr. Juanita reevaluation of Helicobacter pathogen- by the American Gastroenterology markers— is addressing important Merchant has made paradigm-shifting esis and the control of acid secretion in Association (AGA) who awarded her the clinical needs: the ability to differen- contributions to our understanding the context of gastric inflammation. Her Distinguished Achievement Award in tiate lethal cancers from non-lethal of the gastric response to chronic studies have led to the use of develop- Basic Science (2017). disease, reducing overdiagnosis and inflammation, including transcriptional mental paradigms in understanding lowering the number of false-positive control mechanisms in the GI tract. how chronic inflammation alters the In recognition of her seminal work, and false-negative test results. differentiation pattern of epithelial Dr. Merchant was inducted into the
Thomas D . Wang, MD PhD National Academy of Sciences Institute Professor of Gastroenterology and their function and disease pathophys- disease. This includes the generation of of Medicine in 2008. She was installed Chair of the University of Michigan iology, and using high throughput zebrafish porphyria models and using as H. Marvin Pollard Professor of Medical School Department of screening to identify compounds that these models to identify potential Gastrointestinal Sciences in 2008. Molecular and Integrated Physiology. may be used as potential therapy. This therapies. He has been an investigator at the VA work is based on past findings from M. BISHR OMARY, MD, PhD Throughout his career, Dr. Omary has Ann Arbor and Palo Alto Healthcare his laboratory that mutations in K8, H. Marvin Pollard Professor of received many honors, named lec- systems for 28 years. K18 and K19 predispose their carriers Gastroenterology tureships and mentorship awards. He to acute and chronic forms of liver Professor and Chair, Department of Dr. Omary’s research focuses on acute trained many physician scientists and disease and to disease progression. Molecular & Integrative Physiology and chronic liver and pancreatic physiologists who have become leaders disorders as related to the interme- Other current work involves studying in their own right. In 2015 he received M. Bishr Omary, MD, PhD, joined the Chung Owyang, MD 34 diate filament cytoskeleton, genetic the molecular pathogenesis and the AGA Distinguished Mentor Award. Division in 2008 as H. Marvin Pollard modifiers, porphyrias, biomarkers biologic significance of the hepato- He served as the editor-in-chief of of Gastroenterology and Hepatology and therapeutic targets. Current work cyte inclusions called Mallory-Denk Gastroenterology from 2011 to 2016. and Director of the Pollard Institute for bodies. Dr. Omary’s laboratory has Medical Research at the University of focuses on investigating intermediate CHUNG OWYANG, MD identified several critical genetic and Michigan Health System. filament proteins, termed keratin H. Marvin Pollard Professor of posttranslational modifications that polypeptides 8, 18, 19 and 20 (K8/ Internal Medicine Dr. Owyang’s own research interests K18/K19/K20), which are specifically are essential for inclusion formation. have focused on the delineation of neu- expressed in digestive-type epithelia. Additional ongoing studies are aimed Chung Owyang, MD is currently the rohormonal control of digestive func- This includes studying their regulation at understanding the pathogenesis H. Marvin Pollard Professor of Internal tions including pancreatic endocrine through posttranslational modifica- of porphyrias and why some patients Medicine, Professor of Molecular and and exocrine secretions, GI motility tions and associated proteins, defining with porphyria develop end-stage liver Integrative Physiology, Chief, Division and eating behavior. Most recently,
M . Bishr Omary, MD PhD FACULTY LEADERSHIP
his laboratory has focused on the role pancreatitis patients by diminishing and has published more than 300 gastroenterologists who now hold the Division of Gastroenterology and of microbiota in functional bowel CCK-mediated stimulation. Dr. Owyang original research and review articles. In leadership positions in their home Hepatology. diseases, intestinal inflammation and also has a longstanding interest in the recognition of his long and dedicated countries. In recognition of this work, Dr. Nostrant developed the infrastruc- metabolic disorder. His research has physiology and pathophysiology of service to the University of Michigan, he was awarded a Royal College ture for the Division’s clinical opera- provided important insights into the gastrointestinal motility. Among his ob- he received the Distinguished Service of Physicians (Thailand) Honorary tions. In the early 1980s, he formalized pathophysiology and treatment of servations, using isolated cells, muscle Award (2010) and the Paul De Kruif Fellowship and has been given Hon- clinical procedures and systems, many human disease states particularly in the strips and in vivo animal studies, he has Lifetime Achievement Award (2016). orary Professorships by more than 10 still in place today. He also recognized treatment of chronic pancreatitis and demonstrated that somatostatin has top universities in China. At the national level, Dr. Owyang was the increasingly important role endos- irritable bowel syndrome. both excitatory and inhibitory actions in honored by the American Gastroen- WILLIAM D. CHEY, MD copy would play as a major diagnostic myenteric cholinergic transmission and His laboratory characterized a new terological Association (AGA) with the Timothy T. Nostrant Collegiate tool in the field of gastroenterology thus plays a critical role in mediating peptide, CCK-releasing factor, which Distinguished Mentor Award (2011), Professor in Gastroenterology and was integral to the creation of the 35 both limbs of the peristaltic reflex. He is secreted into the intestinal lumen which recognizes an individual for his/ highly successful Medical Procedures further demonstrated that in humans, Dr. Timothy Nostrant joined the U-M in response to food and stimulates her achievement as an outstanding Unit (MPU) at U-M. somatostatin is a potent agent to Department of Medicine as a House CCK release. The pancreatic enzymes mentor over a lifelong career. In 2013, initiate intestinal migrating motor Officer in 1973 and completed his Widely respected for his clinical subsequently secreted into the lumen he received the AGA Julius Friedenwald complexes and thus can be effective residency and Gastroenterology knowledge and passion for education, inactivate CCK-releasing factor, thereby Medal, the highest honor the AGA in treating bowel bacterial overgrowth Fellowship at U-M in 1979. He soon Dr. Nostrant earned numerous awards creating a feedback regulatory loop. bestows on a member. in patients with chronic intestinal joined the faculty and, over the next for his teaching contributions. He This novel observation has provided pseudo-obstruction. Throughout his career Dr. Owyang 36 years, emerged as an outstanding trained over 300 fellows, including the basis for understanding the clinical has actively promoted research and diagnostician, a motivating teacher many of the Division’s key clinical fac- utility of pancreatic enzyme supple- Dr. Owyang has received continuous educational training at the interna- and a visionary leader. In 1981–83, ulty members. He also led the Faculty ments in alleviating pain in chronic NIH funding for more than 30 years, tional level and has trained many Dr. Nostrant served as interim Chief of Diagnostic Unit, a productive consul- tative service within the Department has been elected to the roster of “Best Michigan in 1960. She met Chuck in of Internal Medicine that served as a Doctors” since 2001 and “America’s Top 1958 at a social mixer, and they were national model for the development Doctors” since 2009. In 2010, he was married in 1961. A fellow U-M alum, of the Clinician Scholar track. named one of the “75 Best Gastroen- with a degree in business, Chuck rose terologists in America” by Becker’s ASC through the executive ranks at Ford Dr. Nostrant’s many contributions to Review. Motor Company. Alice taught school, the Division and to the field of gastro- taking a particular interest in children enterology are honored in perpetuity ANNA S.F. LOK, MD, FRCP with special needs; in later years, she with the Timothy T. Nostrant Collegiate Alice Lohrman Andrews Research sold real estate. She was also active as Professorship in Gastroenterology, Professor of Hepatology a national officer in her sorority, Alpha established by Dr. Nostrant’s family William D . Chey, MD The Alice Lohrman Andrews Research Chi Omega. The couple, who shared Anna Lok, MD 36 and colleagues in 2010. uscripts, reviews and book chapters Professorship in Hepatology was estab- a love of U-M football and basketball, Lok’s research toward more effective Today, WILLIAM D. CHEY, MD, holds and served as co-editor-in-chief of the lished by Charles J. “Chuck” and Judy raised three children. treatments and, eventually, a cure. the Timothy T. Nostrant Collegiate American Journal of Gastroenterology Andrews. The professorship is named In the mid-1990s, Alice was diagnosed Professorship. Dr. Chey (Fellowship for Chuck’s late wife, Alice Lohrman In December 2007, the foundation from 2010 to 2016. He also serves on with liver disease. The family sought 1993) directs the GI Physiology Lab- Andrews, who died in 1996 from decided to further support Dr. Lok’s the editorial boards of several other care from world-renowned hepatologist oratory and co-directs the Michigan complications of liver disease. work by establishing a professorship journals. ANNA LOK, MD. When Alice lost her Bowel Control Program. He also runs in Alice’s name in order to advance the A native of Detroit and graduate of life to the disease in 1996, the family an active clinical research group, Dr. Chey has participated in and world-class research in liver disease Redford High School, Alice Lohrman philanthropic organization TUKTAWA which has received funding from directed numerous national and inter- at U-M, made possible by Dr. Lok’s earned her bachelor’s degree in (pronounced “tucked away”) was both federal and private sources. He national continuing medical education leadership of the hepatology team in education from the University of directed to make gifts to support Dr. has authored more than 200 man- programs in gastroenterology, and the Division. FACULTY LEADERSHIP
Dr. Lok continues to hold the Alice all-oral, direct-acting antiviral agents and was inducted into the Department dition to 23 fellows and more than 250 Owyang’s legacy of selfless dedication Lohrman Andrews Research Profes- (DAAs), rather than the standard of Internal Medicine Clinical Excellence staff. Under his leadership, the Division will live on at the University of Michi- sorship in Hepatology today, and her therapy of ribavirin and interferon in 2013. She has been included in the established the University of Michigan gan in perpetuity. New England Journal of Medicine list of “Best Doctors” and “Who’s Who” Center for Gastrointestinal Research, work is transforming how diseases of ( , The Keith S. Henley, MD, for many years and will be president of the first of its kind in the nation. The the liver are diagnosed, managed and 2012; 366:216-224). She is now Collegiate Professorship in AASLD beginning January 1, 2017. Division is one of the most highly treated. Her research focuses on the investigating different combinations Gastroenterology of DAAs that might further shorten recognized groups of gastroenterolo- natural history and treatment of hep- The Chung Owyang, treatment and improve cure rates for gists in the world, noted for innovation, atitis B and C, and the prevention of MD, Professorship in From 1954—when he joined the Uni- additional virus genotypes as well as excellence and leadership in emerging liver cancer. She has published more Gastroenterology versity of Michigan Medical School than 350 papers on viral hepatitis and among patients with advanced liver areas of basic, translational and clinical faculty—until his death in 2010, Keith liver diseases and is the coauthor of disease and those who have failed Chung Owyang, MD, has established research and in clinical care. S. Henley, MD, dedicated himself to 37 the American Association for the Study prior treatment. an international reputation as a leader his research, clinical and teaching To commemorate Dr. Owyang’s of Liver Diseases (AASLD) Practice in gastroenterology over his more duties in the Division of Gastroen- Dr. Lok has received many awards for career, Dr. John Carethers, Chair of Guidelines on Hepatitis B, a reference than quarter-century as Chief of the terology and Hepatology. Today, her work, including the Distinguished the Department of Internal Medicine for physicians all over the world. University of Michigan Division of physicians and researchers across the Scientist Award from the Hepatitis B and the Division have established the Gastroenterology and Hepatology. He country cite Dr. Henley as one of their In a landmark study of hepatitis Foundation in 2008, the Distinguished Chung Owyang, MD, Professorship is the longest-serving GI division chief most valued mentors. C, published in 2012, Dr. Lok and Women Scientist Award from the Amer- in Gastroenterology. This chair will in the country. colleagues showed it was possible to ican Gastroenterological Association support future chiefs of the Division of Dr. Henley was named professor of achieve a sustained virologic response (AGA) in 2008, the Distinguished Ser- Dr. Owyang has overseen the Division’s Gastroenterology and Hepatology. The internal medicine in 1968. He took in patients infected with genotype 1 vice Award from the AASLD in 2011, the growth from a dozen faculty members Chung Owyang, MD, Professorship in over leadership of the Division of of the virus using a combination of AGA’s William Beaumont Prize in 2016, in 1990 to more than 80 today, in ad- Gastroenterology will ensure that Dr. Gastroenterology as chief in 1972 and founded the U-M Hepatology former trainees and the Department sis, genetics and human development became UMMS’ first senior associate co-director of the Joint Institute for Clin- Program that same year, bringing of Internal Medicine. Dr. Henley found and psychosomatic medicine. In 1996, dean for education and global ical and Translational Research between together a highly talented group of the professorship, established in 2008, the New York City-based philanthropic initiatives in 2009. In that role, he the University of Michigan Medical hepatologists. He led the Division as deeply meaningful. foundation selected the University of serves as UMMS lead for the oversight School and Peking University Health chief until 1981 and retired in 1993, Michigan Medical School (UMMS) from and expansion of the education Science Center. The Joint Institute fa- JOSEPH KOLARS, MD although he continued to serve the among 51 competing applicants for the mission and global initiatives. cilitates collaborative research projects Josiah Macy, Jr. Professorship in U-M Medical School in many ways. grant that funded this professorship. and training initiatives between the Health Professions Education Dr. Kolars’ career has been focused schools and their affiliated hospitals. A world-renowned hepatologist, Today, JOSEPH KOLARS, MD on physician education, and he has After Kate Macy Ladd’s father died of Dr. Henley’s primary research (Fellowship 1989), holds the Josiah held a number of leadership roles in He has given lectures and/or conducted yellow fever in 1876 when he was focus during the latter part of his Macy, Jr. Professorship in Health education programs for medical stu- classes in many parts of the world, just 38, she was moved to establish 38 career and into retirement was the Professions Education. Dr. Kolars dents, residents and fellows, including including China, Malaysia, Thailand, a medical research foundation in his development of an infrastructure program director of one of the largest India, Peru, Germany, Pakistan, South honor. The Josiah Macy Jr. Founda- to aid in the education and care of internal medicine residencies in the Africa, Ghana, Uganda, Tanzania and tion supports programs designed to hepatitis patients in Vietnam and United States. His scholarship has Vietnam. For more than three years, improve the education of physicians other countries afflicted with high largely emphasized educational out- he lived in Shanghai with his family and enhance the representation of incidences of the disease. comes, measurements of competency, to establish a new healthcare system minorities in the healthcare profession. faculty development and effective that could also serve as a learning In 2007, Dr. Henley’s colleagues Ladd’s dedicated financial support learning venues. site for local physicians. He has also began work to endow the Keith S. enabled the foundation to award grants worked with the Bill and Melinda Gates Henley, MD, Collegiate Professorship Dr. Kolars has extensive international that advanced research in such areas as Foundation on education systems that in Gastroenterology. Dr. Henley and experience, including numerous faculty traumatic shock and war-related psychi- will build human resource capacity to his family contributed generously development programs worldwide. atric disorders, aging and arteriosclero- transform health. to the fund, as did many colleagues, In 2010, he was appointed inaugural
Joseph Kolars, MD FACULTY LEADERSHIP
Established Lectureships
The Division of Gastroenterology and Hepatology and the Department of Internal Medicine a physician can continue to grow and and admired by his students. He was have established four lectureships to honor individuals who have made significant develop through myriad careers to an outstanding diagnostician, skillful contributions to clinical care, teaching and research . Each Lectureship is used to bring a provide care and service to patients endoscopist and compassionate leading expert to the University of Michigan to present a lecture . wherever they may be. teacher. His tremendous clinical knowledge and judgment made him Tadataka “Tachi” Yamada, MD, Today, this center is in its 30 year of new pharmaceutical entities which The Division of Gastroenterology and the “go-to” person in the Division of KBE Lectureship – world leaders in continuous funding from the NIH. promise relief from suffering for the Hepatology developed this lectureship Gastroenterology and Hepatology gastrointestinal investigation Dr. Yamada’s exceptional success as a poorest people of the world. to honor Dr. Yamada. Each year a world- and one of the most popular Division Chief led to his appointment renowned leader in Gastrointestinal In 1983, Dr. Tadataka (Tachi) Yamada For his significant contributions, gastroenterologists in Michigan. as the John G. Searle Professor and Sciences is invited to present the was recruited by Dr. William Kelley Dr. Yamada received an honorary Chair of the Department of Internal Yamada Lecture. Dr. Nostrant had a strong passion to join the University of Michigan appointment as Knight Commander of Medicine in 1990. In February 1996, for medical education. Whether in 39 as Professor of Internal Medicine the Most Excellent Order of the British Timothy T. Nostrant, MD he was named as the President of the the ward or classroom, he selflessly and Chief of Gastroenterology. Tachi Empire (KBE). He was also a member of Lectureship in Gastroenterology – Healthcare Division and Executive provided consultation and teaching approached his new position with the President’s Council of Advisors on national leaders in education Director of SmithKline Beecham. to students, fellows and junior great enthusiasm and fervor. Under Science and Technology. Subsequently, be became Chair faculty members. He trained more his leadership, the Division became Dr. Nostrant came to the University of Research and Development for Dr. Yamada remains actively involved than 300 fellows who are now the premier division in the country. of Michigan as a house officer in GlaxoSmithKline. In 2005, Bill Gates in academics as Adjunct Professor practicing in 33 states. Dr. Nostrant The Digestive Disease Center, funded 1973. He completed a fellowship in selected Dr. Yamada to run the Bill at the University of Michigan, received numerous awards for his by the NIH with Dr. Yamada as the PI gastroenterology in 1979 and then and Melinda Gates Foundation Global maintaining a tie with his roots to teaching contributions, including was critical to the development of the became a faculty member. Throughout Health Program. Under his leadership, serve as a bridge between academia, the Outstanding Clinician Award Michigan Gastrointestinal Peptide his career, he exhibited the attributes the Gates Foundation engaged in the industry and philanthropy. In many from the Office of the Dean in 2008, Research Center, the first NIH Peptide of a master clinician: trusted by his clinical development of 70 vaccine and ways, Tachi Yamada exemplifies how AGA Distinguished Clinician Award Research Center in the country. patients, respected by his colleagues and was a charter member of the at the Royal Free was the “Mecca of hepatologist at the University of Terry M. Logan, RN Department of Internal Medicine Hepatology” for referring physicians Michigan and Anna Lok, MD, who has Gastroenterology Nurse Clinical Excellence Society. worldwide and THE Liver Center for been Director of Clinical Hepatology Education Fund – national leaders to trainees in Hepatology from the at the University of Michigan since support nursing education To honor Dr. Nostrant, the Division 1960s to the 1980s. Dr. Sherlock 1995 both received their training established the Timothy T. Nostrant For 20 years, Terry served at the published more than 600 papers, and in hepatology under the tutelage of Lectureship in Gastroenterology. University of Michigan in several wrote or edited over 25 books. She Dame Sheila Sherlock. Each year a world leader in clinical capacities, most notably in the GI trained more than 300 physicians and gastroenterology is invited to present To honor her mentor, Dr. Anna Lok outpatient clinic. Terry was well investigators, many of whom went on the Nostrant Lecture. and the Divisions of Gastroenterology known for her diligence, compassion, to be directors of liver units all over and Hepatology established this exemplary service and commitment Dame Sheila Sherlock MD the world. She remained very close to 40 lectureship. to nursing. This fund serves to Visiting Lectureship in all her trainees and considered every establish within the Division a Hepatology – world leaders in one as part of the “Sherlock Family”. Each year a world leader in hepatology legacy of excellence in nursing care hepatology In 1978, Dr. Sherlock was knighted will be invited to present the Dame and to support visits to U-M by key by the Queen of England as “Dame Sheila Sherlock, MD Lecture on an In 1959, Dr. Sheila Sherlock was leaders who will share the latest Commander of the British Empire” for important topic in liver disorders. advancements in patient care, clinical appointed to the Chair of the her contributions to medicine. Department of Medicine at the Royal research and technology in nursing. Free Hospital School of Medicine. She Education and training of other was the first woman to be appointed physicians in liver diseases has to the Chair of Medicine in a British been a cornerstone of Dr. Sherlock’s medical school. Dr. Sherlock’s unit work. Keith Henley, MD, the first Clinical Programs 41 Committed to Clinical Excellence
Gastroenterologists and hepatologists at the University of Michigan specialize in the the Department of Internal Medicine’s prevention, diagnosis and treatment of disorders of the digestive tract and liver . With more Clinical Excellence Society. than 75 specialists in the Division, it is the second-largest academic practice in the United States . Last year, for example, we performed about 30,000 endoscopic procedures in our Much of our clinical approach is state-of-the-art facilities . supported by clinical trials, providing access to important studies for Over the years we have built a We emphasize practice through Manometry laboratories in the world thousands of patients each year who culture of partnership with referring scientific discovery. Each program in and cutting-edge endoscopy units, our seek new and innovative clinical physicians and their patients. Our our Division works at the forefront experts collaborate with our referring options. This is particularly true for clinicians are committed to this of research in its subspecialty. With physicians to diagnose many obscure challenging conditions like Crohn’s collaboration to provide a seamless tens of millions of dollars of National gastrointestinal and liver disorders and colitis (60 studies), hepatology 42 continuum of care. With this Institutes of Health funding every and provide minimally invasive (30 studies) and functional bowel integrated approach, we deliver year, our scientists and clinicians treatment and relief. disease (20 studies). optimal and patient-friendly treatment work together to provide the most Our gifted clinical team of faculty, and maintain close interaction with advanced and innovative treatment Through careful planning and the fellows, mid-level providers, nurses, other specialties within the University options and care. This establishes the successful recruitment of key providers dietitians and staff work diligently of Michigan Health System. Through University of Michigan as a preferred and staff, our clinical services have to care for our patients. They are our our new patient liaison service we referral center throughout the state continued to increase significantly most important resource. More than provide a one-stop multidisciplinary and around the world. since 1990. We have specifically one-third of our faculty are recognized service to manage many complex focused in clinical areas such as liver Armed with one of the most as Best Physicians in America. Nine of gastrointestinal and liver disorders. transplant, Wilson disease, hepatitis, sophisticated GI Physiology and our faculty have been inducted into liver cancer, drug induced liver injury, CLINICAL PROGRAMS
Crohn’s and colitis, functional bowel Canton – Hepatology, General GI, esophagus (EMR, banding, dilation), disease, pancreas and biliary system, Esophageal stomach, interventional endoscopy small bowel and general GI. We have Dexter – General, IBS (EMR, ERCP, EUS, POEM), Crohn’s determined that these challenging and colitis and small bowel (capsule East Ann Arbor – General GI, IBD, areas are best served by developing endoscopy, double balloon en- Geriatric GI focused, multidisciplinary teams. teroscopy). Facilities have increased The number of clinic locations has Grand Rapids – Advanced from one each at U-M and VA to five increased from one each at the U-M Hepatology (UH, VA, East, Livonia, Northville), and VA to 16 clinics. Livonia – General, Pancreatic Biliary supporting a 472 percent increase in procedures, from 5,518 in FY1991 to UH Taubman – GI all programs Northville – All programs over 30,000 in FY2016. 43 UH Taubman – Hepatology and Saline – General GI, IBD Transplant VA - GI Lumen Our GI Physiology program has grown dramatically as we are better able Cancer Center – Liver Cancer VA - Hepatology to measure and quantify the impact Cancer Center – Cancer Genetics Over this same period of time, clinic of electrical signals and pathways, Women’s and Children’s – visits increased 255 percent, from acidity and muscle contractions. Michigan Bowel Control 11,693 in FY1991 to 41,532 in While providing only a few hundred Briarwood – General GI, IBS FY2016. diagnostic tests in FY1991, our GI Physiology Laboratory now provides Brighton – IBD, Hepatology, IBS, Endoscopic programs have similarly over 7,000 tests each year. General developed in focused areas of the To better meet the needs of our To meet the Medical Center’s plan for patients, we are continuing to expand expansion, we expect to recruit many to new locations throughout the region additional faculty and staff. as well as within Ann Arbor: Growth projections for clinic and West Ann Arbor (FY18) endoscopy activity are shown in the Primary and Subspecialty Clinics following charts. Brighton Health Center (FY19) Endoscopy, ORs, Clinics East Ann Arbor Phase II (FY22) 44 Endoscopy, ORs, Clinics New 230 Bed Patient Tower (FY23) 120 incremental beds Northville II (FY24) ORs, Clinics CLINICAL PROGRAMS
With our robust infrastructure, world-class faculty and a firm commitment to serve, we offer patients the most advanced, 45 safest and proven medical treatments for gastrointestinal and liver disorders . This is the Michigan Difference! GI Leadership Lays Foundation for Clinical Research
A significant milestone in the history of the Division of Gastroenterology was the establishment expert in drug-induced liver disease, for more than 170 departments and in the late 1960s of the Clinical Research Unit (CRU) . Headed by ARTHUR FRENCH, MD, the CRU led the Center in the 1990s. JOHN W. divisions; it also collaborates through was one of only six such entities in the country supported by the National Institutes of Health WILEY, MD, an expert in neurophys- a nationwide consortium to advance to provide much-needed infrastructure for clinical investigations . iology and the brain-gut axis, served clinical and translational discoveries as director from 1999 to 2012. During that improve care of patients. Dr. French’s own research focused on • a collaboration between demonstrating that oral zinc is his tenure, the GCRC was funded by malabsorption. In collaboration with PAUL WATKINS, MD, JOSEPH an effective therapy for Wilson the largest NIH grant based at the ROBERT J. BOLT, MD, he developed KOLARS, MD, and ROBERT disease. Treatment with zinc University of Michigan medical campus the multiple-retrieving small bowel FONTANA, MD in the Division of acetate remains the standard of at that time. biopsy tube, which enabled them Gastroenterology that established care for Wilson disease today; to perform the first intestinal biopsy an important role for the gut Dr. Wiley also served as president of the • a collaboration between HARI 46 and to make the association between lumen-based cytochrome p450 GRCR Program Directors Association. CONJEEVARAM, MD, MSc, in flattened villi and malabsorption in enzymes in drug metabolism During his tenure, he helped guide the the Division of Gastroenterology celiac disease. and modulation of this pathway transition of the GCRC model to the and CHUCK BURANT, MD, PhD, by specific foods including current model, supported by the NIH In the 1970s, the CRU transitioned to in the Division of Endocrinology grapefruit Clinical Translational Sciences Award the NIH General Clinical Research Cen- and Metabolism, examining the (CTSA) program. This innovative model ter (GCRC) model. It played a pivotal • the collaboration between pathophysiology of non-alcoholic allows more flexible allocation of role in supporting numerous studies GEORGE BREWER, MD, in the fatty liver disease. resources to support clinical research at Arthur French, MD focusing on the GI tract including: Division of Human Genetics, and Over the years the Division’s faculty the institutional level. Today, the CTSA FRED ASKARI, MD, PhD, in the have provided strong leadership of grant at the University of Michigan Division of Gastroenterology, the GCRC. DR. WATKINS, a renowned serves as the clinical research hub CLINICAL PROGRAMS
Rare Care: MULTIDISCIPLINARY CLINIC FOR PATIENTS WITH WILSON DISEASE
A rare, hereditary metabolic liver disorder that impedes the cellular transport of copper, “Wilson disease presents clinicians Wilson disease affects about 6,000 individuals in the United States . Delays in diagnosis are with many questions and special common . But as copper collects in liver, brain and other tissues, the disease can cause a situations that vary from patient to range of dangerous symptoms easily mistaken for those of many neurologic and psychiatric patient. That’s part of the challenge disorders . and why it’s so important to learn how to recognize and diagnose it,” said Dr. “Many doctors might only see one deficiency and applied the findings to specialist and patient coordinator have Askari. “There’s nothing more gratify- or two patients with Wilson disease Wilson disease. His team’s work was extensive experience working with ing to me than for a colleague to call in their career,” said FRED ASKARI, instrumental in translating a scientific families affected by Wilson disease. me up and say, ‘Hey, I diagnosed a MD, PhD, director of the University discovery into an FDA-approved therapy In addition to treating patients and case of Wilson disease.’” of Michigan Wilson Disease Center with zinc acetate, which has since been conducting ongoing research, Dr. of Excellence. “In contrast, we see adopted worldwide. 47 Askari and colleagues teach U-M hundreds, and we learn more from Treatment at U-M also includes highly medical students, residents and every one.” multidisciplinary care. Patients may be Gastroenterology and Liver Transplant The U-M has a history of successful seen by adult or pediatric hepatolo- fellows about the disease and consult management and treatment of Wilson gists, neurologists, speech pathol- with physicians globally. Efforts are disease dating back to the 1990s, ogists, liver transplant specialists, underway to establish international when—in the course of conducting re- dietitians, genetic counselors and care networks and telemedicine search on sickle cell anemia—a team of psychiatrists. The Center’s laboratory programs to further develop physician physicians led by DR. GEORGE BREW- technicians specialize in urinary expertise and reduce the need for hD P ER D, discovered that zinc caused copper copper quantitation, and a nurse patients to travel long distances. , M kari Fred As Clinical Hepatology: PROVIDING CUTTING-EDGE, COMPASSIONATE, MULTIDISCIPLINARY CARE FOR LIVER DISEASE
DRUG INDUCED LIVER With 15 faculty and close to 12,000 patient visits annually, the Hepatology Program at the INJURY, ACUTE LIVER University of Michigan Health System is one of the largest in the nation . One of the oldest clinical hepatology programs, it offers expertise in a wide range of liver diseases, including drug- FAILURE, WILSON induced liver injury, acute liver failure, cirrhosis, fatty liver/NAFLD, viral hepatitis and liver cancer. DISEASE, CIRRHOSIS Since its start in the 1970s, the program has achieved national and international recognition . CARE LIVER CANCER Initially housed at the main out to patients and providing care Similarly, through the Liver Tumor Clinic, University Hospital campus, the in many areas,” noted ANNA LOK, patient care is coordinated among Hepatology Program now has MD, FRCP, Director of Clinical surgeons, oncologists, hepatologists and clinics in Brighton, Canton, Hepatology. radiologists. A longstanding Liver Tumor Northville and, monthly, in Board now offers referring physicians Focused clinics offer specialized 48 Grand Rapids, with other an opportunity to participate virtually VIRAL HEPATITIS care prospective Michigan in meetings to discuss treatment locations under The Hepatology Program has also options, allowing some patients to get consideration. developed three highly sought, consultative care without having to multidisciplinary clinics in Liver travel. The Hepatology Program runs a “Over time, you Transplant, Liver Tumor and Wilson second Liver Tumor Clinic and Tumor can’t stay in one Disease. Through the Liver Transplant Board at the VA Ann Arbor Healthcare place; rather Clinic, established 21 years ago, System. LIVER than ask patients patients have access to hepatologists, to come to us, Staffed by a multidisciplinary care team, TRANSPLANTATION transplant surgeons, social workers, FATTY LIVER/ we are going the Wilson Disease Center of Excellence psychiatrists and dietitians in one visit. NAFLD CLINICAL PROGRAMS
runs a monthly Wilson Disease Clinic. Training hepatologists Dr. Lok herself has trained over 20 U-M sources. Several faculty head “Our physicians and physician- Based on individual need, patients can worldwide fellows from all parts of the globe large, multi-center, clinical research scientists have emerged as leaders at see speech pathologists, neurologists, since she joined the University of networks funded by the National the national level,” Dr. Lok said. “As The Division’s three-year dietitians, genetic counselors and Michigan faculty in 1995. Several of Institutes of Health, including a result, our patients benefit by Gastroenterology Fellowship includes psychiatrists in one visit. Laboratory these fellows are now full professors, those focused on acute liver failure, having access to experimental training in all aspects of hepatology. technicians supporting the Center are and some are chiefs of medicine or drug-induced liver injury, hepatitis therapies and effective new In addition, the Division offers a specially trained in the quantification gastroenterology divisions. B and biomarkers for early diagnosis treatment approaches. The fourth-year Transplant Hepatology of copper, and a nurse specialist and of hepatocellular carcinoma. Faculty new insights and knowledge Fellowship. More than a dozen fellows Leadership in clinical research patient coordinator focus on the unique across the Hepatology Program generated by our faculty have graduated from this program, needs of individuals and families With a broad research portfolio, the publish an average of 64 articles in benefit not just our and many are now faculty in other affected by this rare disease. Hepatology Program’s investigations peer-reviewed journals annually. patients but also patients academic hepatology programs. 49 span scientific, clinical and health worldwide. The large Groundbreaking research into hepatitis services research. Research efforts number of former fellows C is leading to new all-oral drug are funded by the National Institutes in practice in more than 10 regimens, with significantly reduced of Health (R01, U01, K08, R03), states in the United States side effects and improved cure rates U.S. Department of Veterans Affairs, and in 10 countries magnify for patients. Other faculty have made American Association for the the impact of the Michigan pioneering discoveries of genetic Study of Liver Diseases, American Hepatology Program on our field markers associated with obesity and Gastroenterological Association and and on patients with liver diseases A fatty liver. Yet others have provided n the Doris Duke Charitable Foundation, around the world.” na valuable data on liver organ allocation, Lo as well as philanthropic, industry and k, M D, leading to changes in national policies. FRCP Claudia Dionne HEARING THE WORD “CURE”
For Claudia Dionne, it’s hard to remember life before what she calls “the discovery”: simple, with minimal side effects,” the devastating news that she had viral hepatitis. said Dr. Lok. “The current challenge is to make sure patients are diagnosed “I just knew my life had changed often with serious side effects. Perhaps “Claudia was one of the first patients and referred early.” forever,” she said. “I went for my yearly even more frustrating has been the in the world to be cured with a combi- checkup like I had done forever and low cure rate: typically only 40 to 50 nation of oral pills,” said Dr. Lok. “She Claudia was skeptical at first, wavering ever and ever—and lo and behold, percent of patients clear the virus. was declared cured in early 2012, two between hope and disbelief. “A I was at dinner that night when my years before any of the combinations couple of pills a day and that’s it?” she But hepatologists at the University doctor called and broke the news: I of oral pills were approved. This is wondered. It seemed too easy. And of Michigan, including Dr. Anna Lok, had hepatitis C.” a benefit of participating in clinical then she heard the word from Dr. Lok led the first clinical trial that proved trials, although not all trials lead to she wasn’t sure she would ever hear. Hepatitis C affects some three to four that a combination of oral drugs can 50 positive results and some carry risks. “Dr. Lok never used that word with me, million Americans, causing eradicate hepatitis C even in the most As researchers, we are forever grateful until one day she looked at me and inflammation and damage difficult cases. The discovery allows to patients who put their faith in said, ‘You’re cured.’” to the liver. For the patients like Claudia to clear the virus, us and undertake risks that benefit past few years, the preventing the threat of liver failure Because Claudia was diagnosed early, science and other patients with the only treatment and liver cancer. she will not need to worry about same disease.” has been a cirrhosis or liver cancer in the future. The findings from that first study grueling In the past three years, 10 direct- In fact, she has been discharged from were published in the New England combina- acting antiviral agents have the liver clinic or, in Dr. Lok’s words, Journal of Medicine (2012; 366:216- tion of been approved for use in various “Claudia has graduated from my care.” 224) and paved the way for testing inject- combinations, and the vast majority of and approval of other combinations able patients can expect a 90 to 95 percent of direct-acting antiviral agents for medi- cure rate after only 12 weeks of pills. hepatitis C. cines, “Treatment now is highly effective and Patient Story CLINICAL PROGRAMS
The History of Liver Transplant
The University of Michigan Liver was appointed medical director; large number of dedicated individuals Transplant Program was one of the additional innovations since that time including nurses, mid-level providers, first 10 such programs established in have included the utilization of living GI fellows, therapeutic endoscopists and the United States. The first transplant donor transplantation, use of deceased a cadre of collaborators in pathology, done on August 2, 1985 required a cardiac donors, testing of extracorporeal radiology and cardiology. The program team of more than 50 staff including liver support devices and major continues to evolve, with one-year surgeons, nurses, perfusionists and improvements in the control of hepatitis patient survival rates of over 90 percent myriad support staff. Over time, the B and C both pre- and post-transplant. and more durable graft function with Drs. Darrell A. Campbell Jr., duration of the operation, the need Throughout the history of the program, improved patient clinical outcomes due Jeremiah G. Turcotte and for blood products and other aspects success has required the input of a to lower levels of immunosuppression. Donald Dafoe performed of medical and surgical innovation the first pancreas and liver 51 led to a tremendous expansion of transplants at U-M this intervention from a little over 400 transplants nationally per year in the early 1980s to nearly 7,500 per year in 2016. Milestones in the The first transplant University of Michigan program was done August 2, include seminal studies by Drs. Henley and Lucey describing successful outcomes in patients with alcoholic cirrhosis, hepatitis B infection and 1985 liver cancer. In 2002, Dr. Fontana
The first University of Michigan liver transplant team Keeping the Focus: PROVIDING PATIENT-CENTERED CARE TO LIVER TRANSPLANT PATIENTS
Now in its 30th year, the University of Michigan Liver Transplant Program was the first program established in Michigan and one of the first 10 in the United States. Since 1986, the program’s faculty have performed more than 2,250 transplants, including more than 350 pediatric liver transplants . In addition to volume, quality out- of over 100 staff who touch the life of social worker, dietitian, pharmacist and comes help differentiate the U-M pro- each individual patient. nursing coordinator all in one visit. gram. The one-year patient survival rate Improving access to “Our multidisciplinary clinics were in the most recent publicly reported multidisciplinary care designed to facilitate patient- cohort reached 91.5 percent, despite a centered care,” said Dr. Fontana. “The waitlist of increasingly ill patients. One of the earliest programs to individuals who come to us are facing 52 embrace multidisciplinary clinics in the “Our recent outcomes are fairly remark- a lot of medical challenges, and we 1990s, the program’s hepatologists able in light of the increasing acuity of want to make their visits as easy as began seeing patients hand in hand patients being referred for transplanta- possible—for them and for their family with surgeons, social workers and other tion,” said ROBERT J. FONTANA, MD, members alike.” practitioners in the outpatient clinic. who served as the Medical Director of Working in close collaboration with the In 2013, toward that same patient- the U-M Liver Transplant Program since surgical director of the liver transplant centered goal, the Liver Transplant 2002. The outcomes reflect the work program, DR. JOHN MAGEE, today, Program opened a new, state-of- and dedication of a highly coordinated the multidisciplinary nature of the the-art transplant clinic on the first team of medical and surgical experts program has greatly expanded. Pa- floor of the Taubman Center. The from multiple specialties and a team tients can see a hepatologist, surgeon, clinic includes nutrition therapy, CLINICAL PROGRAMS
phlebotomy, radiology, a pharmacy “Our goal when we establish these the late 1980s, Drs. Michael Lucey and and facilities for some outpatient clinics is to help the area medical com- Keith Henley helped define the criteria procedures, including paracentesis, munities provide the best possible care and process to offer liver transplanta- liver elastography, intravenous locally,” said Dr. Fontana. In addition, a tion to patients with alcoholic liver infusions and blood transfusions. series of Continuing Medical Education disease. These seminal studies (CME) programs focusing on liver have influenced the practice of Reaching out to Michigan disease have been held in various loca- transplantation over the past patients and their doctors tions throughout the state for the past 25 years. To further facilitate access to care, 20 years to keep practitioners apprised Dr. Fontana, an expert in patients can see the Division’s liver of the latest advances in clinical care drug-induced liver disease, specialists through additional Ad- and research. “Through the educational currently co-chairs two large 53 vanced Hepatology clinics, held on the programs, local physicians expand National Institutes of Health west side of the state in Grand Rapids their expertise and the services they (NIH) research networks, and Midland in the Thumb area . In offer, which they, and their patients, including the Acute Liver addition, Hepatology faculty currently appreciate,” he added. Failure Study Group. Patients see patients at University of Michigan Research findings inform care with acute liver failure (ALF) Health System satellite clinics in Brigh- and drug-induced liver injury ton, Northville and Canton to provide Research being conducted by the have access to the latest therapies more convenient and easier access Division’s faculty guides the care R to improve their likelihood of survival. ob options for both general hepatology patients receive and provides access to er The U-M program was a key contributor t J and liver transplant patients. new and experimental treatments. In . Fo to a study that demonstrated improved nta na, MD transplant-free survival in ALF patients therapy to clear HCV infection, and in The U-M Liver Transplant Program is Faculty in the U-M Liver Transplant who received IV N-acetylcysteine 2014 Dr. Fontana treated the first liver also a leader in the conditioning of Program are active in policy develop- compared to placebo. Studies utilizing transplant recipient with a combina- donor organs, including extracorporeal ment related to transplantation, and a non-invasive breath test to identify tion of phase 2 drugs, which have now membrane oxygenation perfusion for U-M recently served as headquarters those that will recover with supportive become the standard of care. organs from high-risk donors. A clinical for the Scientific Registry of Transplant care as soon as possible are currently trial with 10 other transplant sites is Recipients. Research protocols offering Dr Lok was also the lead investigator underway. In addition, studies have also being started on normothermic the latest treatments for patients with for the NIH hepatitis B virus orthotopic been done defining the role of extracorporeal perfusion. hepatitis B, alcoholic hepatitis and liver transplantation (HBV OLT) extracorporeal artificial liver support for cholangiocarcinoma are underway. study that defined the role of oral “If successful, this novel approach could patients with chronic liver failure in the antiviral agents for patients with enable us to substantially expand the The U- M program has also been a intensive care unit. 54 HBV both before and after liver donor supply and provide transplants leader in the use of radiation therapy Dr. Fontana and his colleagues have transplantation. That work has led to to more patients, saving a lot more and other neo-adjuvant treatments also been involved in a number of new immunoprophylaxis strategies lives,” said Dr. Fontana. for the management of patients with pioneering studies on the use of that are simpler to administer and liver cancer that have led to improved Other studies are underway to direct-acting antiviral agents (DAAs) more convenient for patients. Drs. outcomes and more patients becoming develop parameters for pre-operative to improve the treatment of hepatitis Lok and Fontana continue to work eligible for transplant. risk assessments and to reduce the C (HCV), the leading cause of liver on better therapies for patients with amount of blood products needed “We work on many fronts to advance failure culminating in transplanta- compensated chronic HBV as well for transfusion using rotational the field,” said Dr. Fontana, “and that tion. Fellow Division researcher DR. in the context of the ongoing NIH thromboelastometry (ROTEM). enables us to keep fully focused on ANNA S. LOK, was the first author Hepatitis B Research Network. always improving the care we provide of a study reporting the use of DAA to all our patients.” CLINICAL PROGRAMS
George Magulak, DDS FEELING “BLESSED WITH GOOD FORTUNE AND EXTRAORDINARY CARE”
After George Magulak, DDS, was diagnosed with primary biliary cholangitis (PBC) Arbor at 3 a.m. He received a new in 2004 during a routine physical and blood test, he threw himself into learning as liver that day. much as he could about this rare autoimmune disease. Nearing the one-year anniversary of the Determined to stave off the damage Soon after, Dr. Magulak met Dr. Robert better there, given the lower demand transplant, Dr. Magulak is optimistic that necessitates liver transplant, Fontana, Medical Director of the for organs in the region. and grateful to the donor and family Dr. Magulak changed his diet and University of Michigan Liver Transplant who saved his life and to the U-M Liver Rapidly deteriorating, Dr. Magulak exercise routines to better support his Program at an organ donation Transplant Program. “The hepatology received a call one morning at his liver, and continued seeing patients in fundraiser. Following the event, Dr. and transplant team has treated me hotel room in South Carolina from a his busy Michigan dental practice. He Fontana reviewed Dr. Magulak’s with the utmost empathy, respect and former patient. The son of a family hiked, golfed and skiied with family records and delivered dire news: he professionalism....They included me in friend of another patient, who had and friends. was going to need a liver transplant every decision concerning my care. I 55 died in a car crash in Michigan, and needed to get onto the waiting feel very blessed with the good fortune In 2011, signs of was made aware that the young list right away. and extraordinary care I’ve had.” advancing disease man’s family wanted to direct the began emerging, Dr. Magulak was accepted to the donation of his organs. The patient although doctors transplant list at U-M and later at the remembered his dentist’s moving didn’t think Medical University of South Carolina. letter and tracked down Dr. Magulak. they were He wrote a letter to his patients, sold his After the U-M transplant coordinator related practice and moved south, believing called hours later, Dr. Magulak to PBC. the likelihood of being selected was boarded a plane and arrived in Ann
Patient Story H. MARVIN POLLARD, MD BASIL I. HIRSCHOWITZ, MD FIRST FIBEROPTIC GASTROSCOPE
In 1954, Dr. Basil I. Hirschowitz (foreground), a South African trained in gastroenterology at British hospitals, came to the University of Michigan for a fellowship under Dr . H . Marvin Pollard (on the left), head of the Division of Gastroenterology . Collaborating with Dr . C . 56 Wilbur Peters, an optics expert in the U-M Physics Department, they created the world’s first fully flexible fiberoptic gastroscope and used it to view the interior of stomachs of patients with ulcers . By the 1970s, fiberoptic endoscopy had reinvigorated the field of gastroenterology, transforming the diagnosis and treatment of diseases ranging from esophageal cancer to Crohn’s disease, and leading the way to today’s array of endoscopic and noninvasive surgeries .
Illustration: Bill Burgard CLINICAL PROGRAMS
Medical Procedures Unit: BUILT UPON A FOUNDATION OF INNOVATION
Established in 1991 under the leadership of DR. TACHI YAMADA, then division chief, and developing ERCP-induced pancreatitis, DR. TIMOTHY NOSTRANT, acting chief prior to Dr . Yamada, the University of Michigan Medical which occurs in about 15 percent Procedures Unit (MPU) serves patients from all over Michigan and the Midwest . of high-risk patients undergoing the procedure, and 5-10 percent of average-risk patients. The MPU is built upon a solid history esophageal endoscopic mucosal has been critical to our GI Division since This has become the of innovation in endoscopy within the resection, endoscopic retrograde more than 50 percent of our clinical standard of practice Division of Gastroenterology. In 1957, cholangiopancreatography, endoscopic activity is endoscopy, and much of the in most medical DR. BASIL HIRSCHOWITZ led the ultrasound and liver biopsy, among endoscopy training for our fellows centers. team that invented the first flexible many others. occurs in the MPU.” fiberoptic endoscope. In 1961 DRS. “Ongoing research Comprising 11 endoscopy rooms, two A full-time endoscopy research ROBERT BOLT and ARTHUR FRENCH and clinical advances 57 procedure rooms for fluoroscopy and coordinator facilitates many studies demonstrated a simplified multiple- nurtured by the MPU the GI Physiology and Manometry in the MPU, and the Unit will support retrieving small bowel biopsy tube that have supported Laboratory—as well as several satellite clinical studies of new endoscope enabled them to perform the first small greater numbers of procedure units at other U-M Health systems and peptide probes developed bowel biopsy and seminal research on complex procedures System centers—MPU facilities by Professor THOMAS WANG, MD, the association between small bowel being performed on performed some 30,000 procedures PhD. In work published in the New morphology and malabsorption. patients who require in 2016. England Journal of Medicine (2012; more complicated Grace Elta, MD Today, the MPU provides a number 366: 1414-1422), MPU investigators “The MPU was one of the first ‘modern’ care, and we expect this trend to contin- of routine and, increasingly, more found that a single prophylactic endoscopy units in the country. It was ue since the University of Michigan is a advanced diagnostic and therapeutic dose of indomethacin administered a real showcase,” said GRACE ELTA, major referral center for gastrointestinal procedures, including balloon-assisted immediately post-procedure can MD, MPU director since 2002. “And it diseases,” said Dr. Elta. Basil Hirschowitz, MD, PhD endoscopy, capsule endoscopy, significantly reduce the risk of Motility Disorders: BRINGING SCIENTIFIC DISCOVERY TO PATIENT CARE
With 10 faculty specializing in research and treatment of motility disorders, the U-M Motility Disorders Group (MDG) is the largest and one of the most versatile groups of motility experts in the country . The group includes JOHN W. WILEY, MD (visceral hypersensitivity and IBS), WILLIAM D. CHEY, MD (food allergy and IBS), WILLIAM HASLER, MD and ALLEN LEE, MD (gastroparesis), BORKO NOJKOV, MD (non-ulcer dyspepsia), RICHARD SAAD, MD, MSc (pelvic floor disorders and colonic inertia), STACY MENEES, MD, MSc (women’s health and pelvic floor disorders), SHANTI ESWARAN, MD (low-FODMAP diet and IBS), JOEL RUBENSTEIN, MD, MSc (esophageal motility disorders, GERD and Barrett’s Esophagus) and CHUNG OWYANG, MD (intestinal pseudo- obstruction, microbiome and IBS). Most of our motility experts are cases referred from other gastroen- disorders. In collaboration with 58 opinion leaders in their subspecial- terologists. Using a holistic approach, our surgical colleagues and using ties and provide care through several our IBS experts achieve a high rate of state-of-the-art technology offered by specialized clinical programs. The success in treatment. the GI Physiology and Manometry gastroparesis program is a key par- Laboratory, the U-M Motility Program The U-M GI Motility Disorders Program ticipant in the National Gastroparesis treats numerous patients with slow was the first to use Octreotide to Registry and specializes in innovative transit constipation who do not treat intestinal pseudo-obstruction. treatments of refractory gastroparesis respond to traditional laxatives. The Currently large populations of and cyclic vomiting. Up to 30 percent Michigan Bowel Control Program uses intestinal pseudo-obstruction patients of patients seen in the GI outpa- a multidisciplinary approach to treat come from all regions of the United tient service have irritable bowel pelvic floor disorders and sphincter States to seek innovative treatments syndrome (IBS). Many are difficult abnormalities. for this group of difficult motility CLINICAL PROGRAMS
GI Physiology and Manometry • GI manometric studies record (RDs) with specialized knowledge “GI motility disorders Laboratory gastrointestinal motility and help in low-FODMAP diets evaluate are common and many diagnose intestinal pseudo- nutritional needs and recommend The GI Physiology and Manometry are debilitating. At the obstruction and to differentiate dietary changes to reduce symptoms. Laboratory under the leadership of neuropathic form myogenic The RDs also recommend enteral and University of Michigan, Dr. William Chey and Jason Baker is disorders. parenteral nutrition regimens when we have the expertise, located in the Medical Procedures Unit needed. The program’s behavioral (MPU). The lab performs unique diag- These tests are not available in many experience and state-of- psychologist specializes in the nostic tests for patients with motility medical centers in the United States, the-art diagnostic facilities management of chronic pain and disorders: and only the University of Michigan can provide behavior therapy and to diagnose and manage offers all three in one location. • Comprehensive diagnostic tech- hypnosis. Our physical therapists the most complex GI 59 Coordinated Team approach nology including video capsule, have specialized knowledge in pelvic motility disorders ”. smart pill and colon capsules. floor disorders and anal sphincter A team of experts from different abnormalities and work with patients — Chung Owyang, MD • Electrogastrography (EGG) disciplines provides optimal care for suffering from pelvic muscle dyssyn- monitors gastric pacemaker patients with difficult motility disor- ergia and fecal incontinence. activities and is used as a tool ders. The Department of Gastrointes- for the diagnosis of tachygastric tinal Surgery provides services such Research and Innovation arrhythmias, a condition often as placement of pacemakers in the With strong National Institutes of observed in patients with nausea stomach and insertion of intestinal Health research funding, physicians and vomiting. feeding tubes for refractory gast- and physician scientists within the roparesis. Two registered dietitians MDG have contributed to the scientific to treat them mean that we have been disorder—the first time a gut peptide trial showing that a low-FODMAP literature in many ways, including quite successful in addressing some had been used to treat a GI disorder (fermentable, oligosaccharides, demonstration of new therapies and very complex issues for our patients,” (New England Journal of Medicine, disaccharides, monosaccharides and treatment approaches, all of which said Dr. Owyang, who heads the group 1991; 325:1461-1467). More polyols) diet can improve symptoms improve the lives of patients cared for and the Motility Disorders Clinic. recently, Dr. Chey’s research indicates and quality of life for patients with in the Motility Disorders Clinic. that Naloxegol may be beneficial IBS (Gastroenterology, 2016; 150 New approaches to motility to treat opiod-induced constipation (4): S172). “Our inquiries into the underlying failure (New England Journal of Medicine, causes of these disorders and how best “We’re achieving cure rates on the Since many motility disorders have 2014; 370: 2387-2396). Similarly, order of 70 to 75 percent using diet neurological underpinnings, they can Dr. Hasler’s clinical interest in alone,” said Dr. Owyang. 60 be extremely difficult to diagnose and diabetic gastroparesis has led to the treat. The group uses its unique exper- exploration of new possibilities for Work by the Motility Disorders Group John W . Wiley, MD tise: original clinical research, frequent electronic pacing of the stomach. investigators is also continuing to clinical and drug trials and state-of- point to abnormalities in gut bacteria, patients. The findings are informing Solving the puzzle of functional the use of antibiotics and probiotics to the-art diagnostic equipment and bowel disease or dysbiosis, as a cause of IBS. Re- procedures to provide new treatments searchers are looking at host-microbi- treat the disorder. and therapies to these patients. New research at the University of ome interactions to better understand “The microbiome as a target of therapy Michigan is also leading to the use of how the microbiome affects motility, Work related to intestinal pseudo- is the subject of several investigations,” diet as form of treatment for irritable regulates permeability of the GI obstruction, conducted by Dr. said Dr. Owyang. “It’s a telling example bowel syndrome (IBS) in many tract’s mucosal lining and affects Owyang in the early 1990s, led to of how research is driving our clinical patients. Drs. Chey and Eswaran have mood, including the depression and the use of Octreotide to treat the practice.” William Hasler, MD published the first rigorous clinical anxiety commonly experienced by IBS CLINICAL PROGRAMS
“Work performed by the motility group led to the discovery of new drugs for the treatment of GI motility disorders. These discoveries significantly impacted clinical practice, becoming the standard of practice for treatment of this group of GI disorders” — Chung Owyang, MD
Intestinal Manometric Tracings in a Normal Subject and a Pa- tient with Scleroderma. Effect of Octreotide on Intestinal Motility and Bacterial Overgrowth in Scleroderma The manometric recordings in 61 normal subjects showed propa- Hani C. Soudah, MD, William L. Hasler, MD, and Chung Owyang, MD gative intestinal patterns during N Engl J Med 1991; 325:1461-1467 November 21, 1991 DOI: 10.1056/ fasting. In contrast, the patients NEJM199111213252102 with scleroderma who had pseudoobstruction and bacterial Naloxegol for Opioid-Induced Constipation in Patients with Noncancer overgrowth did not have any Pain spontaneous duodenal phase 3 activity . Octreotide evoked William D. Chey, MD, Lynn Webster, MD, Mark Sostek, MD, Jaakko Lappalainen, intestinal phase 3 complexes MD, PhD, Peter N. Barker, PhD, and Jan Tack, MD, PhD that were qualitatively similar N Engl J Med 2014; 370:2387-2396June 19, 2014DOI: 10.1056/ Back row: Mark McDermott, Jacob Kurlander MD, Jason Baker to the complexes evoked by NEJMoa1310246 Front row: Kathy Dayne, Joel Rubenstein MD, MSc, William D . Chey MD, Joan Chen MD, octreotide in the normal subject . MSc, Hanan Al-Shahly This observation eventually led to the use of octreotide to treat patients with intestinal pseu- doobstruction . Michigan Bowel Control Program REALIZING A VISION FOR COORDINATED CARE AND RESEARCH ACROSS DISCIPLINES
Treating bowel control problems such as severe constipation and fecal incontinence involves diagnosing, managing and treating multiple specialties and treatment approaches . The University of Michigan is home to one of bowel control disorders in their the few programs nationwide to offer highly coordinated, multidisciplinary care to patients patients. Other gastroenterologists who suffer from bowel control disorders . working in the MBCP include DRS. SHANTI ESWARAN, ALLEN LEE, research into causes and treatments STACY MENEES and BORKO and developing novel approaches to NOJKOV. helping our patients,” said WILLIAM D. CHEY, MD, who co-founded the “We knew we could do better for our Michigan Bowel Control Program patients if we put our heads together (MBCP) program in 2005 and current- and developed coordinated, fully 62 ly serves as medical director. integrated care plans,” said Dr. Chey. Dr. Chey and colleagues DEE The program has grown FENNER, MD, a professor of tremendously over the past 16 years, gynecology, and RICK SAAD, MD, from about 50 new patient referrals Associate Professor of Medicine, the first year to more than 500 in William D . Chey, MD specializing in constipation and Rick Saad, MD, MS 2015. Patients have come from all pelvic floor disorders, established across the United States and other the program to carry out their vision: countries as well. “Our physicians not only are experts in gastroenterologists, urogynecologists to break down siloes and bring caring for individuals with bowel con- and colorectal surgeons—who would Follow-up care is a critical part of together a team of specialists— trol problems; they’re also conducting provide innovative approaches to the MBCP’s work. A dedicated team CLINICAL PROGRAMS
gastroenterologist STACY MENEES, Using a model of the pelvis, Dr . MD, is leading a trial comparing Fenner, with nurse Anne Mcleod, dietary fiber supplementation to helps a patient understand the a low-FODMAP diet (fermentable relationship between constipa- oligosaccharides, disaccharides, tion and pelvic organ prolapse . monosaccharides and polyols) for the treatment of fecal incontinence. Trials also are underway for a novel glove-based manometry system Dr. Chey developed for the evaluation of anal sphincter function. 63 Stacy Menees, MD, MSc “When we established the MBCP,” Dr. of nurse concierges helps patients Chey said, “we set out to continually implement and follow their care improve the care we deliver by bring- plans, all essential steps toward ing disciplines together and digging improving outcomes. deeper into why patients suffer from the symptoms they do. As a result, Rigorous scientific and clinical we continually gain new insights into research by MBCP faculty also better and better ways to help resolve contributes to advancements in them.” care. Dr. Chey, in collaboration with Solving the Puzzle of IBS: A NEW STANDARD OF CARE EMERGES
Successful management of irritable bowel syndrome (IBS) requires a comprehensive approach Emerging evidence suggests diets free to care that combines the expertise of multiple health care professionals who specialize in of gluten and diets low in fermentable dietary and behavioral counseling, in addition to medical treatments and pharmaceutical oligosaccharides, disaccharides, therapies . monosaccharides and polyols— commonly known as the low-FODMAP “Over the last five years, we have “If you asked any of the gastroenter- Puzzle Piece A: diet—can be beneficial for patients identified and assembled the puzzle ologists at the University of Michigan Expert Dietary Counseling with IBS. The low-FODMAP diet, in pieces that allow us to offer a more five years ago, diet and behavior For many patients, symptoms of IBS particular, is a fairly complicated diet, holistic approach to patients with IBS,” would have been very low on their are triggered by what they eat, and Dr. Chey noted. Patients following said WILLIAM D. CHEY, MD, who is a list of priorities,” Dr. Chey said. “Now, increasingly, physicians are recognizing this diet require the assistance of widely known expert on IBS. our gastroenterologists say they the critical role of diet in managing professional nutrition specialists. 64 can’t imagine how we did it before That means thinking critically about the symptoms of IBS. Unfortunately, we had these assets in place. It has “I think most physicians right now how diet, lifestyle and behavior might few physicians are trained to provide really been a transformation in care are trying to manage diet by giving interact to bring about the symptoms nutritional counseling. over the past five years, and we’re patients a sheet of paper with a list of of IBS. “We consider how we might extremely proud of that.” “The reality is most gastroenterologists foods to eliminate, and that’s simply in- offer interventions for each of those receive little to no training in nutrition adequate,” he said. “Diets are definitely components of care to really maximize Successful long-term management of or the practical elements of administer- more comprehensive and complicated the benefit of medical treatments for IBS, it turns out, is a multidisciplinary ing diet therapies for patients with IBS,” than can be conveyed with a sheet of patients with IBS,” he said. affair. W Dr. Chey said. paper—even potentially dangerous ill iam if not administered in a medically D . Ch responsible way.” ey, MD CLINICAL PROGRAMS
As a result, many diets do not work gastroenterologists to administer MEGAN RIEHL, PsyD, is a clinical as well in clinical practice as evidence dietary interventions in a medically health psychologist at the U-M, and from clinical trials might suggest, responsible way,” he added. the state’s only psychologist with a he noted. In order to achieve similar specific focus on GI disorders. IBS This is just one of the many areas where results, diets need to be administered is the most common GI illness that the University of Michigan sets itself by experts who understand gastroin- brings patients to her clinic. “About 65 apart: the Division of Gastroenterology testinal nutrition and know how to help percent of patients present with IBS or has the equivalent of four GI dietitians— patients incorporate dietary changes a functional bowel disorder,” she said. two full-time GI dietitians at University into their daily routines, he said. Hospital and others who assist in caring Typically, patients are referred to Dr. “One of the problems right now is for patients at offsite facilities that Riehl by a gastroenterologist who may there aren’t that many trained GI are part of the University of Michigan have exhausted medical treatment 65 dietitians around. There are dietitians, Health System. options and/or believes a patient but they’re not specially trained in would benefit from stress and anxiety Behavioral Therapies gastroenterology,” Dr. Chey said. management techniques. Increasing- Found Instrumental for IBS ly, behavioral therapy is becoming “One of the things that needs to Management routine in the treatment of patients happen on a national level to improve The Behavioral Health Program at the with IBS. “As more patients become the quality of care for patients with IBS University of Michigan offers patients aware of the GI behavioral health is to train a population of dietitians with GI disorders an opportunity to service, more of them are asking their that have expertise in GI disorders, address symptoms with a specially gastroenterologists for a referral to the and to have them work closely with trained GI psychologist. program,” Dr. Riehl said.
Dr . Megan Riehl explains to a patient about brain-gut interaction . Behavioral therapy is personalized for “CBT involves helping patients find Puzzle Piece B: Focused For example, cognitive-behavioral each patient, but in general, therapy is new ways of thinking and behaving Behavioral Therapy therapy, hypnosis and interpersonal designed to help patients deal with the to help manage stressful situations,” psychotherapy can be very beneficial Just as diet has come into focus as an “uncontrollable” and “unpredictable” Dr. Riehl explained. For example, for patients with IBS. But these thera- essential aspect of treatment for IBS, aspects of IBS. Patients learn relaxation patients with IBS may experience pies require specialized training—even so have behavior and lifestyle. The and stress management techniques anxiety-provoking thoughts such as, more specialized than many clinical way in which an individual responds they can apply to everyday life stressors. “Where will a bathroom be if I need psychologists are equipped to offer. to stress can greatly affect symptoms it?”, “What if I’m having symptoms “My goal is to help patients learn to of IBS. Puzzle Piece C: Medications and before a big exam or presentation?” cope effectively and efficiently with Research or “How will I ever be intimate with a “There are certainly some things that worries that can interfere with social, partner?” CBT teaches patients how to gastroenterologists can recommend “Medications still play the really 66 occupational and family life,” Dr. manage emotional responses to these to try to facilitate changes in lifestyle important role,” Dr. Chey noted. Riehl said. potentially stress-inducing situations. or behavior,” Dr. Chey said. For Therapy for IBS is symptom-driven, Gut-Directed Therapies example, yoga or a regular exercise “My goal is to aid patients in self- depending on a patient’s needs. “For plan can be very helpful in managing Most often, behavioral therapy for pa- management strategies that benefit patients with mild or moderate IBS stressors that can lead to the symp- tients with IBS involves interventions GI health, emotional well-being and symptoms, sometimes all they need toms of IBS. based on cognitive-behavioral therapy overall quality of life,” Dr. Riehl said. is a little bit of medication, such as (CBT), a short-term, collaborative treat- “People learn tools to create long- But as in the case of diet, many an over-the-counter antidiarrheal or ment that is focused on a patient’s term change, without remaining in gastroenterologists are not trained to antispasmodic on an as-needed basis, current problems. treatment for long periods of time. It’s provide more advanced behavioral and they’ll do just fine. Patients with very rewarding.” counseling to patients with IBS. more severe IBS symptoms will almost CLINICAL PROGRAMS
LOW-FODMAP DIET
always need one or more medica- necessary to provide support in nutri- MEATS DAIRY AND EGGS GRAINS tions,” Dr. Chey said. tion and behavior, as well as “vertically AVOID ENJOY AVOID ENJOY AVOID ENJOY integrate research from the bench to Notably, Dr. Chey’s group has been the bedside,” Dr. Chey said. “So we’re • Chorizo • Beef • Milk • Lactose-free • Wheat • Gluten-free involved in some capacity in the not only providing excellent quality of • Sausages • Chicken • Sour cream milk (gluten) baked goods research that led to the FDA approval care for patients, we’re also striving to • Processed • Lamb • Yogurt • Lactose-free • Barley • Brown rice of all five prescription drugs indicated make discoveries that will transform meat • Pork • Cream yogurt • Bran cereals • Oatmeal for the treatment of IBS in the United the role of diet and behavior and • Turkey cheese • Butter • Rye • Quinoa States. how they interact with medications to • Seafood • Ice cream • Cheese • Semolina • Corn tortilla Because of its dedication to research, maximize benefit for patients with IBS • Eggs the University of Michigan gives its and other functional disorders.” 67 patients the opportunity to participate in ongoing IBS clinical trials, such as “I think most physicians those involving the low-FODMAP diet right now are trying to and an upcoming trial of prebiotics in manage diet by giving patients with IBS. patients a sheet of paper Building on this foundation in GI with a list of foods to nutrition and behavioral therapy, a new effort—the Digestive Disorders eliminate, and that’s simply Nutrition and Lifestyle Program—will inadequate ”. bring together the diverse elements — William D . Chey, MD LOW-FODMAP DIET
FRUITS CONDIMENTS LEGUMES VEGETABLES AVOID ENJOY AVOID ENJOY AVOID ENJOY AVOID ENJOY Patients following this • Apples • Bananas • Honey •d Mustar • Kidney beans • Chick peas • Garlic • Carrots diet require • Avocado • Blueberries • Jam • Ketchup • Lima beans • Lentils • Onions • Green beans the assistance • Cherries • Cantaloupe • Pesto sauce • Barbecue • Butter beans • Cauliflower • Lettuce of professional • Grapefruit • Grapes • Relish sauce • Black beans • Celery • Bell peppers nutrition • Peaches • Lemon • Stock cubes • Chocolate • Split peas • Mushrooms • Squash specialists . • Mayonnaise • Soy beans • Peanut butter 68 CLINICAL PROGRAMS
Morgan’s Story
Morgan Blenkhorn missed high Morgan’s symptoms started a few tors told her she was exhibiting IBS tose mixture, water and a breath test. symptoms. She continues to dance school several times because of symp- months after a severe food poisoning symptoms and gave her probiotics for A few weeks after her appointment, and play sports. Last summer, she toms that doctors said were related to incident in 2010 during her junior treatment. But a chance meeting on Dr. Chey spoke with Morgan and her was even able to study abroad in the irritable bowel syndrome (IBS). year of high school. She endured an airplane between her father and family and told them the diagnosis: Netherlands. pain, particularly while dancing and gastroenterologist William Chey, MD, fructose intolerance. “Anything I would eat, I would get “It was beautiful, life-changing, playing soccer. She eventually turned would lead to a series of interviews, sick,” she said. “I was nauseous; I “We all cried,” Morgan said. something I didn’t think I’d ever be to apples and honey for relief, but they tests and a final diagnosis from the would have headaches, stomach- able to do before because I couldn’t only made her symptoms worse. University of Michigan’s gastroenterol- Finally, Control … aches; I had diarrhea and I was just ill sit in a car for two hours without ogy and dietitian team. all day, every day.” “It was really hard having to come This experience was unlike any other having to pull over,” she said. “Biking home from school being sick all the Her first visit to the University of for Morgan. The team’s gastroenter- 10 miles to work and backpacking time, waking up sick and trying Michigan was in 2013, during the ologists were briefed on her case alone through Germany were things 69 to go to school and act like fall of her sophomore year of college. and knew exactly how to address her I thought I’d never be able to do everything was fine,” She had several blood tests done issues. The dietitian they referred her because I was so sick.” she said. before meeting with Dr. Chey. Upon to mapped out a zero-fructose eating Morgan is finishing her fourth year her first appointment with him, she plan that catered to her vegetarian A Chance at Grand Valley State University in was promptly told what to expect: diet and her love for veggies, pasta Meeting Allendale, Michigan, with another year a fructose test, a lactose test, more and curry. Bears Fruit left to complete her special education blood tests and an endoscopy. “They listened to my specific wants, degree. She still checks in with Dr. Over the According to Morgan, Dr. Chey went not just me as a patient but me as Chey every once in a while. For now, next above and beyond preliminary tests to Morgan,” she said. she hopes to be accepted into Grand three find the root of the problem. The test Valley’s Consortium for Overseas years, that changed it all, she said, was the After being diagnosed with fructose Student Teaching program in Ireland several fructose test, which consisted of a fruc- intolerance, Morgan now plans her this summer. doc- own meals and has full control of her Patient Story LAUREL R. FISHER, MD SMALL BOWEL PROGRAM: CAPSULE ENDOSCOPY AND BALLOON-ASSISTED ENTEROSCOPY
An early pioneer in small bowel imaging technology, the Division of Gastroenterology at the University of Michigan first offered capsule endoscopy to patients in 2001, rapidly becoming a national leader 70 in the field of small bowel enteroscopy. In 2007, the Division performed the first therapeutic double-balloon enteroscopy in the state of Michigan, and the University of Michigan remains the only referral center statewide . To date, the Division has performed over 5,300 capsule endoscopy and nearly 2,000 double balloon procedures and is poised to continue its commitment to advanced technology for enhancing patient care .
Illustration: Bill Burgard CLINICAL PROGRAMS
Small Bowel Disorders Program CUTTING-EDGE PROCEDURES TRANSFORM PATIENT CARE
“The only comprehensive small bowel program in the state, the University of Michigan Small Bowel Disorders Program (SBDP) is transforming how patients with small bowel problems are diagnosed and treated—and changing their quality of life in the process ”—. Dr. Laurel Fisher, First Director of the Michigan Small Bowel Program Capsule endoscopy to visualize particularly those with suspected doscopically treated, thereby avoiding the small bowel GI bleeding. This often changes the conventional surgery. in-hospital care patients receive—and Since 2001, the SBDP has been The U-M SBDP is the only tertiary refer- helps to prevent future hospitalizations. performing video capsule endoscopy ral center in the state offering DBE. (VCE) studies in order to view the ap- Double-balloon enteroscopy for To date, physicians have performed proximately 20- to 25-foot-long small diagnosis and treatment 71 intestine for diagnostic purposes. The Once the source of bleeding is found program’s physicians have performed through VCE, many patients undergo over 5,300 studies, one of the highest double balloon enteroscopy (DBE). volumes in both the state and the This intervention is used for both nation, according to MICHAEL RICE, diagnostic and therapeutic purposes, MD, director of the Small Bowel including biopsy, removal of lesions Disorders Program. and dilation of strictures. DBE has In addition to performing VCE for changed the paradigm of small bowel outpatients, physicians are increasingly disease management; many of the performing VCE studies on inpatients, SBDP’s patients are now able to be en-
Dr . Mimi Takami nearly 2,000 procedures over the past For a decade, specialized endoscopists 10 years, among the highest volume at U-M have used DBE to success- in the country. The program employs fully evaluate the small intestine four DBE enteroscopists and continues to manage small bowel bleeding, to expand., DRS. MIMI TAKAMI, tumors, inflammatory bowel diseases MICHAEL RICE, NEIL SHETH and and other small intestinal conditions. ANDREW READ. Increasing numbers of patients with complicated post-surgical altered “DBE is an important tool in the anatomy, including Roux-en-Y gastric armamentarium to manage patients bypass anatomy, are referred to U-M with suspected GI bleeding, since for DBE to assist in the evaluation and 72 small bowel bleeding accounts management of disorders involving for about 5 to 10 percent of those bypassed segments of bowel. cases,” said Dr. Rice. “Using VCE to evaluate our inpatients soon after “DBE has revolutionized our ability to presentation affords the opportunity provide therapeutics in the man- to identify the source of bleeding agement of this growing patient early on. As a result, we can capitalize population,” said Rice. on the opportunity to have a patient Specialized endoscopists in the U-M undergo an endoscopic therapeutic SBDP have been able to visualize and procedure with DBE during the same provide therapy for complications hospital stay.” CLINICAL PROGRAMS
including bleeding in the bypassed tolerate advancement of their diet, of expertise. Faculty from institutions “It takes a dedicated and comprehen- portions of the stomach, duodenum improve their quality of life and limit throughout the country have come to sive program to best help patients and and beyond the jejuno-jejunostomy, their need for surgery. the U-M SBDP to gain that expertise to advance the field,” said Dr. Rice. which are typically well out of reach from the program’s highly specialized “In the not-so-distant past, prior to In addition, patients with Peutz- of traditional endoscopes. The DBE physicians. Training on both VCE and VCE and DBE, patients with small Jegher’s Syndrome (PJS) develop platform also enables successful DBE are also being incorporated into bowel disorders lived with re- multiple large hamartomatous polyps negotiation of the sharp angulations GI fellowship training. current hospitalizations, blood throughout their small intestine and of the bypassed intestine to facilitate transfusions and the resigna- are at risk for many complications. At the forefront of endoscopic DBE-assisted ERCP to address bile tion that this suffering was Using DBE, U-M specialists can research duct stones and other pancreaticobi- inherent in their condition. proactively and successfully resect liary disorders. The SBDP’s large database of VCE and Now, because of programs these large polyps endoscopically 73 patient data is providing an important like this one, we’re able to Physicians in the U-M SBDP have via an oral, rectal or bi-directional platform upon which to conduct offer our patients endoscop- helped Crohn’s disease patients with approach. DBE with polypectomy has research, and studies have described ic options that can make a small bowel strictures avoid surgery helped patients avert the complications and defined indications for VCE use big difference in their quality and the subsequent risks of short of PJS including intussusception, GI in patients with celiac disease, small of life.” bowel syndrome. Using DBE, endos- bleeding as well as the risks of surgery bowel strictures and suspected small copists have successfully performed and short-bowel syndrome. bowel bleeding. In the near future, stricture dilation using a controlled DBE is a complex procedure that the SBDP also will be participating in radial expansion balloon through the takes a significant amount of time to a multi-center clinical trial involving lengthy enteroscope. The procedure perform and requires a high degree colon capsule endoscopy. MD has helped numerous patients ice, Michael R Inflammatory Bowel Disease Program GROWTH ENHANCES PATIENT-CENTERED CARE AND ACCESS TO NEW THERAPIES
The seriousness and complexity of inflammatory bowel disease (IBD) pose unique challenges well-timed surgical therapy can reduce to both patients and their physicians, challenges that require highly specialized expertise and the amount of intestine that needs to a multidisciplinary approach to long-term management and treatment . be removed. This reduces the long-term risk of short gut, a feared complication The Inflammatory Bowel Disease In addition to improved access to of several new anti-inflammatory of poorly controlled IBD. The team, Program (IBDP) at the University of physicians, patients—many of whom therapies in the anti-JAK, IL-23, and with the patient at the center, develops Michigan is internationally recog- have not responded to previous SMAD-7 pathways are encouraging, coordinated treatment plans and can nized for its team—now 12 faculty treatments—also have access to and investigators are looking toward make more informed decisions based strong—that focuses specifically on experimental and cutting-edge next-generation agents that not only on objective predictors of disease IBD care and IBD-related scientific, therapies. The U-M IBDP is one of the control inflammation but could also progression. clinical and outcomes research. largest IBD clinical trial centers in the reverse fibrosis. 74 The program has added seven new world, and patients can be referred Given the complexity of IBD, patient In addition, new research tools are faculty members in the past five by their own doctors directly to the education is a critical part of disease being developed to assess the degree years alone. trials. To facilitate referrals to trials, management. The IBDP recently of bowel damage to better determine the IBDP recently instituted a simple revamped its patient education “Expanding the scope of our clinical which patients have refractory damage fax process that mirrors the standard materials based on guidance from its practice enables us to accommodate and should consider surgery. A joint clinic referral process. patient advisory board. New educa- more patients and meet the demand clinic between colorectal surgeons and P tional videos and other materials now e from referring physicians,” said Current research includes studies of gastroenterologists specializing in IBD te r feature clinicians and patients sharing H PETER HIGGINS, MD, PhD, MSc i , novel therapies, of how to optimize is taking that research and using it to gg their perspectives on a variety of spe- in who directs the program. “Most approved therapies and how to help patients and their doctors weigh s, M cific issues around living with IBD. D, P newly referred patients now can be predict which drugs are more likely to surgical and non-surgical options. In hD, MSc seen within a week.” work for particular patients in order many cases, the coordination of cut- “Patients love it,” said Dr. Higgins. to personalize care. Clinical trials ting-edge medical therapy for IBD and “There is a huge learning curve with CLINICAL PROGRAMS
Clinic Visits Taubman, Northville, East Ann Arbor, Brighton, Briarwood, Dexter, Canton, Livonia, Saline Routine Follow-up Clinic or High-Risk Follow-up: Actively Flaring: Telemedicine Close monitoring program Levels of Care
Additional Services University of Michigan Crohn’s and Colitis Team Weekly meetings: Ambulatory Diagnostics + GI Behavioral Case conferences, journal Treatment Unit an IBD diagnosis, and newer patients gins, “and we’re also doing the work Health club, research updates 75 appreciate learning from experienced that’s changing how clinicians all over Psychologist patients in addition to their doctor.” the world will treat IBD in the future.” Michigan Short Stay Unit The program has also created a large As an example, the IBDP recently Combined IBD + CR surgery and growing series of “IBD School” developed a severe ulcerative colitis clinic Wednesdays videos that have been viewed more protocol based on new evidence and GI Nutrition ED + Inpatient Care than 250,000 times on YouTube. shared it publicly on the web. “Med- Not only has the IBD program grown ical centers around the country are IBD Study Coordinators in scope; it also has grown in impact. using it now,” Dr. Higgins added, “and Severe UC Protocol “We are delivering a consistently high so we’re able to have a positive impact Home Infusions (Home Med) level of care to our outpatients and on many more patients than we could inpatients and reaching more patients possibly see in our own program.” CD Postop Protocol throughout Michigan,” said Dr. Hig- GRACE H. ELTA, MD ERCP: ENDOSCOPIC THERAPY FOR THE BILIARY AND PANCREATIC DUCTS
ERCP was first performed as a diagnostic procedure in the late 1970s at the University of Michigan. In 1982, biliary sphincterotomy for stone extraction was added . The field of ERCP in the treatment of pancreatic and biliary disorders grew dramatically 76 after that and now includes pancreatic endotherapy and numerous biliary tract treatments . Examples include biliary manometry, stent placement, intraductal lithotripsy, cholangioscopy, intraductal ultrasound, tissue sampling, stricture dilation, transenteral pseudocyst drainage and necrosectomy . These new treatment modalities significantly reduce the need for invasive surgeries . CLINICAL PROGRAMS
Interventional Endoscopy Program: BEYOND PANCREATIC AND BILIARY CARE
A specialty group within the Division, the University of Michigan Interventional Endoscopy for care of inpatients and outpatients Program (IEP) performs advanced endoscopic procedures to diagnose and treat disorders with this condition. The aim of the in- not only of the pancreas and bile ducts but also the esophagus and colon, and leads clinical vestigations is to decrease emergen- research initiatives to continually evolve clinical practice . cy department use and readmission, to reduce inpatient length of stay and The IEP comprises nine faculty: “The IEP and our patient volumes Through a rigorous auditing process, to improve patients’ quality of life. DRS. AARTI OZA-BEDI, GRACE ELTA, have grown phenomenally,” said the IEP was recognized for its RYAN LAW, JAMES M. SCHEIMAN, DR. MICHELLE ANDERSON. “And high-quality, multidisciplinary care— DR. JAMES SCHEIMAN, director of ANOOP PRABHU, STACY MENEES, those high volumes enable ongoing integrating gastroenterologists, inter- Endoscopic Research and Director of ERIK-JAN WAMSTEKER, RICHARD expertise and skill levels that make ventional radiologists, surgeons, pain the Advanced Endoscopy Fellowship S. KWON and MICHELLE A. these complicated procedures safer management services and psychosocial Program, is working with colleagues ANDERSON, who serves as physician and more effective for our patients.” support—and advancing research into in the U-M College of Engineering to 77 lead. pancreatitis and related conditions. Recognized for excellence in develop a sensor technique to deter- mine stent patency. Dr. Scheiman is The team has led the use of multidisciplinary pancreatitis Dr. Anderson has led development also involved in ongoing clinical tri- endoscopic ultrasound (EUS) and care and research of national guidelines for the care of als to lower the risk of ERCP-induced endoscopic retrograde cholan patients with painful chronic pancre- The IEP is also the first and to date the pancreatitis, which occurs in about giopancreatography (ERCP), as well atitis (Pancreatology, 2015; Apr 3: only program in Michigan to be desig- 25 percent of patients undergoing as other complex procedures. The IEP 14(4): 1968-78). Additional research nated a National Pancreas Foundation the procedure. In work published in was the first in Michigan to offer EUS is underway into pain in chronic pan- Center of Excellence for acute and the New England Journal of Medicine and to use it therapeutically. creatitis and EUS. Key findings will chronic pancreatitis. (2012; 366:1414-1422), investiga- inform additional clinical guidelines tors found that a single prophylactic dose of indomethacin administered DR. STACY MENEES is studying EUS esophageal cancer and in Barrett’s “With our expertise,” said Dr. Ander- immediately post-procedure can examination findings in patients with Esophagus with dysplasia. The IEP son, “we’re not only able to take care significantly reduce the risk. BRCA, an inherited genetic mutation also is one of few places in the state to of patients with more complex needs; that places patients at risk for both perform peroral endoscopic myotomy we’re also able to do the research Improving care in pancreatic breast and pancreatic cancer. The goal (also known as POEM) for achalasia required to continually advance the cancer of this project is to identify features that and intra-operative ERCP through treatments we can offer them.” Clinicians in the IEP work closely with predict risk and to guide screening rec- laparoscopic gastrostomy in patients clinicians in the U-M Comprehensive ommendations. DR. RICHARD KWON with prior gastric bypass. Cancer Center and recently instituted is using morphomics to conduct risk One of the added advantages of the a clinical protocol for the endoscopic assessments for patients with cystic IEP at the University of Michigan is the placement of fiducials in pancreatic neoplasms of the pancreas who are at 78 provision of “on-site” pathology at the cancer patients who will undergo risk for pancreatic cancer. Michelle A . An time of a procedure. This helps ensure der son radiation therapy. The procedure , M Broadening procedures and adequate samples are obtained, there- D enables higher and more accurately treatment options , M by reducing the number of potential S targeted doses of radiation and c procedures and improving the patient helps reduce radiation exposure of The IEP clinicians perform interven- experience. surrounding organs and tissues. tional endoscopic procedures for a wide range of GI disorders, beyond Improved care quality and patient To help with pain control in pancre- the pancreatobiliary system. Such experience are the goals of all IEP atic cancer, IEP physicians are one of procedures include endoscopic mu- clinical and research efforts, and the few centers in the state that perform cosal resection and ablation in early program is equipped to achieve them. celiac plexus neurolysis.
Acinar Web
Bioartography com. CLINICAL PROGRAMS
Bryan Stump, DDS GOOD COMMUNICATION BRINGS HOPE AND EASIER DECISION-MAKING
When Bryan Stump, DDS, was diagnosed with pancreatic cancer, his primary care enzymes in his blood were approach- physician referred him to a gastroenterologist at the University of Michigan Medical ing normal levels. School. Dr. Stump met with MICHELLE A. ANDERSON, MD, MSc, who, two days later, placed Dr. Stump is now symptom- and med- a stent in Dr. Stump’s bile duct to relieve some of his symptoms. The blocked duct ication-free. He sees Dr. Anderson just was impairing drainage of bile, leading to severe itching and jaundice. once a year to make sure the masses At the same visit, Dr. Anderson “but Dr. Anderson started giving me problem. However, if Dr. Stump did haven’t returned. And he’s back to performed an endoscopic ultra- hope. ‘This could be better than what indeed have cancer, three months work full time at his dental practice, sound-guided biopsy of the pancreas. we were thinking,’” he recalled her might mean metastasis to other parts something he wasn’t sure he’d be When it came back negative for saying. of the body. able to do again. cancer, she called Dr. Stump back to Dr. Anderson had begun to suspect “Needless to say, it was a hard repeat the procedure. That biopsy “It was definitely a life-changing 79 Michelle A . An Dr. Stump might have been suffering decision,” said Dr. Stump, “but Dr. experience, with some big decisions der came back negative as well. son , M not from pancreatic cancer but from a Anderson left it up to me entirely. to make,” said Dr. Stump, “and I D , M “We were perplexed rare autoimmune condition called au- Only after I told her I wanted to try received the best care I’ve ever gotten. S c at first,” said Dr. toimmune pancreatitis. She consulted the steroid treatment did she say, ‘I’m After I saw Dr. Anderson the first time, Stump, whose with colleagues, both at U-M and at glad you said that.’” she and her nurse Terri [Johnson, RN] imaging tests other institutions, and she shared her were in constant contact about test Both patient and doctor were even had showed thoughts with Dr. Stump. results and other things. I was not left gladder about the results. After three masses wondering all the time.” If her diagnosis was right, a months of treatment with steroids, two on his three-month course of oral steroid of the masses had resolved and two pancreas, medications could resolve the others had shrunk dramatically. Liver
Patient Photo Patient Story Cancer Genetics: DEVELOPING NEW WAYS TO IDENTIFY THOSE AT RISK AND PREVENT COLON CANCER
In the United States, colorectal cancer (CRC) is the third most common type of cancer, consequences of the DNA mismatch although, in the vast majority of cases, it is preventable. In her work as director of the University repair system which when affected, of Michigan Cancer Genetics Clinic, ELENA M. STOFFEL, MD, MPH, focuses on new ways to identify is involved in both inherited and individuals with a genetic predisposition to cancer who may benefit from enhanced screening sporadic colorectal cancer. His lab and surveillance in order to prevent CRC . seeks to understand the basic mech- anisms of DNA mismatch repair in The U-M Cancer Genetics Clinic cares lifetime cancer risk exceeds 70 percent Department of Internal Medicine, human cells and investigates the role for more than 250 families with without intervention. studies the pathogenesis of sporadic of inflammation and DNA mismatch genetic syndromes associated with and hereditary colorectal cancer. The The GI Division has a long, illustrious repair regulation. His laboratory has increased risk for developing CRC, laboratory focuses on the function and history of pioneering colon cancer identified that colorectal cancers including familial adenomatous pol- research. In 1995, DR. RICHARD exhibiting increased inflammatory 80 yposis (FAP) and Lynch syndrome, also BOLAND uncovered the role of DNA cells showcase a biomarker called known as hereditary non-polyposis mismatch repair in regulating the EMAST, which appears to be caused colorectal cancer. Through the clinic, G2/s cell cycle checkpoint, and the by MSH3 (DNA mismatch repair gene) Dr. Stoffel and her team coordinate prediction that colon cancer with dysfunction. In addition, Dr. Carethers’ genetic testing to identify individuals microsatellite instability would be laboratory strives to understand possi- who have increased risk for cancer. resistant to chemotherapy. This set the ble biological differences and possible She and her team also coordinate foundation for subsequent studies on approaches to the racial disparity seen clinical trials to investigate the colon cancer genetics. in the morbidity and mortality from effectiveness of screening tests and colorectal cancer. This series of work medications for preventing cancers The laboratory of JOHN M. has elucidated the pathogenesis of from developing in patients whose CARETHERS, MD, Chair of the sporadic and hereditary colorectal John Carethers, MD CLINICAL PROGRAMS
cancer and provides potential preven- Dr. Stoffel has conducted, presented as may be related to characteristics of of chemotherapy in stage II CRC has tative and/or therapeutic targets. an abstract at Digestive Disease Week tumor biology, rather than disparities been a topic of debate, Dr. Stoffel 2016, suggest that one in five patients in screening, medical care or comorbid noted. “And it may be that tumors in Current clinical studies include under 50 diagnosed with CRC may conditions” young people are more aggressive, trials of chemopreventive agents, have an inherited mutation in known and the chemotherapy we use in older including nonsteroidal anti-inflam- Using data from SEER (Surveillance, Ep- cancer susceptibility genes, including patients may or may not be adequate matory drugs, to slow the growth of idemiology and End Results), Dr. Stoffel those that cause Lynch syndrome, FAP for treating the young.” polyps. DRS. TOM WANG and KIM analyzed outcomes for CRC patients un- and other less common syndromes. TURGEON are investigating ways to der 50, and found the survival rate for Further work will investigate molecular use novel endoscopic technologies to “There is a pressing need to find new blacks was lower at every stage of the characteristics of tumors in CRC pa- better visualize the colon and identify ways to identify these people earlier disease and particularly striking among tients under 50 to better understand polyps, since—particularly in Lynch that don’t rely on family history,” said individuals with stage II cancers. why and how the disease develops. 81 syndrome—precancerous polyps can Kim Turgeon, MD Dr. Stoffel. “We’re hypothesizing that tumors in The continued findings from Dr. be small, flat and hard to discern. physicians and gastroenterologists In related work, Dr. Stoffel is also young people under 50 are probably Stoffel’s work will no doubt inform how “What we’ve found in our work is before they develop colorectal cancer.” interested in better understanding different than those in older people, patients at risk of cancer are identified, that the initial clinical criteria and In fact, many CRC patients who are the rising incidence of colon cancer and there also may be differences screened and cared for. “Taking care algorithms used in risk assessment found to carry mutations associated in young people and racial disparities by race in tumor characteristics that of families that have these inherited are not sufficiently sensitive to iden- with hereditary cancer syndromes don’t in incidence and survival. “While col- contribute to racial disparities in CRC mutations and knowing that in the tify everyone who is at risk of colon meet the typical family history criteria. orectal cancer incidence is decreasing outcomes,” said Dr. Stoffel. younger generations we can intervene cancer,” said Dr. Stoffel. “We want to overall, it’s on the rise in younger to prevent cancer is incredibly motivat- One in three patients diagnosed with The findings have important implica- devise better ways for patients at risk patients, and we’re also seeing racial ing,” she said. FAP is the first in their family to develop tions for treatment, since the benefits to be identified by their primary care CRC. Preliminary data from analyses disparities in outcomes that we think Esophageal Disorders Program ADVANCING RESEARCH, ADVANCING CARE
With more than a dozen faculty, the University of Michigan Esophageal Disorders Program (EDP) continues to offer patients new treatment approaches based on discoveries generated through its ongoing clinical research efforts . The EDP treats both routine and com- mation to manometry. Therapeutical- thereby improving food passage from plex disorders, including achalasia, ly, EndoFLIP can be used for dilation, the esophagus to the stomach. Barrett’s Esophagus, swallowing eliminating the radiation exposure Research drives care problems, eosinophilic esophagitis, associated with the conventional esophageal cancer and symptoms of fluoroscopic method. Several investigations are informing gastroesophageal reflux disease re- care for motility-related disorders. The treatment of esophageal motility- fractory to acid-reducing medications. For the past 18 months, the EDP has related disorders has also evolved. 82 been gathering questionnaires about Diagnosing and managing The EDP offers peroral endoscopic symptom severity from patients un- Joan Chen, MD, MSc motility-related disorders myotomy (POEM) for the treatment dergoing esophageal manometry and of achalasia and other spastic For eosinophilic esophagitis (EoE), To define etiology and guide reflux testing. Given the high volume esophageal disorders. This procedure, the EDP is one of several clinical sites treatment of motility-related issues, of procedures—746 and 481, respec- led by DR. RYAN LAW, is analogous conducting a Phase 3 randomized con- the EDP is one of only a very few tively, in 2015—the data are facilitating to the surgical gold standard, trolled trial of oral budesonide solution. centers in the region with physicians several studies led by JOAN CHEN, laparoscopic Heller myotomy. This If approved, it would be the first EoE experienced in the use of EndoFLIP® MD, MSc, including esophagogastric endoscopic procedure involves treatment to receive FDA approval. (Endolumenal Functional Lumen junction outflow obstruction (EGJOO) the creation of a tunnel within Imaging Probe), to measure esopha- and how to discern when the diagno- In close collaboration with allergists the esophageal wall followed by geal distensibility during endoscopy, sis is clinically relevant and warrants and dietitians, the EDP has developed electroincision of the circular muscle, which provides complementary infor- intervention. a 4-food empirical food elimination CLINICAL PROGRAMS
protocol for the most common food a much higher risk of progression to neoplastic cells. The probes are used The tool was developed from the Newly allergies in EoE patients. And data from cancer—on the order of 3 percent per during fluorescent endoscopy, an Diagnosed Barrett’s Esophagus Study a new registry of EoE patients dating year—than among earlier U.S. cohorts. imaging method developed at U-M conducted at U-M and the Ann Arbor back to 2000 in conjunction with The risk was previously believed to be by Dr. Wang. Clinical trials will begin Veterans Affairs Medical Center validated survey instruments are being about tenfold lower. shortly. This network of academic insti- (American Journal of Gastroenter- used in studies to compare treatment tutions combines scientific expertise ology, 2013; 108(3): 353-362). Other research includes studies of sur- outcomes. across diverse campuses to develop A grant from the Department veillance quality in Barrett’s Esophagus new methods for early detection of of Veterans Affairs is support- In fact, the EDP has established patients to identify potential over- and/ esophageal cancer. Early biological ing validation of the tool in registries for a number of esophageal or underutilization of endoscopy over events that drive cancer transformation, additional patient groups. disorders in addition to EoE, including the past 20 years. In a first-of-its-kind improve our understanding of the role dysmotility, reflux and Barrett’s study, EDP investigators also are In summary, we have a 83 of precursor lesions and lead to more Esophagus. Joel Rubenstein, MD, MSc looking at quality of life in Barrett’s comprehensive Esophageal effective cancer surveillance methods. patients who underwent endoscopic Disorders Program. Our “These registries help us develop Barrett’s Esophagus NIH has provided U-M with more than therapy for neoplasia versus controls robust research programs are observational studies and other investigations $6 million in funding over the past five who underwent esophagectomy. supported by federal funding research that will enable development years to support this effort. The registry of Barrett’s Esophagus which drives our state-of-the-art of interventional investigations,” said Through the Barrett’s Esophagus includes nearly 3,000 patients, and has The EDP also has been a leader in help- clinical care. JOEL RUBENSTEIN, MD, MSc, who di- Translational Research Network led to a study looking at the natural ing primary care physicians diagnose rects the Barrett’s Esophagus Program (BETRNet), THOMAS WANG, MD, T history of Barrett’s Esophagus with Barrett’s Esophagus in certain patient h within the EDP. “Registries provide a PhD and Professor of Surgery DAVID om low-grade dysplasia that was presented groups using the Michigan Barrett’s as BEER, PHD W wealth of information that we then use in a lecture at Digestive Disease Week , have developed novel an Esophagus pREdiction Tool (M-BERET). g, M to develop and test hypotheses.” in May 2016. The findings showed peptide sprays that specifically bind to D, PhD Ann Arbor VA Healthcare System: LEVERAGING TECHNOLOGY TO IMPROVE ACCESS, CARE AND OUTCOMES
Finding novel ways to deliver care is a hallmark of the UM-affiliated VA Ann Arbor Healthcare System (VAAAHS). Staffed by University of Michigan Medical School faculty, the VAAAHS is intrinsically driven by the same three-part mission: clinical care, education and research, including basic, clinical and health services investigations . to implement electronic medical Access Network–Extension of Commu- records (EMR). nity Healthcare Outcomes). The goal of the virtual program is to improve “This EMR system is an incredible re- subspecialty care delivery within the source for both patients and physicians VA healthcare system, particularly for that can be harnessed for innovative re- veterans and primary care providers in search and for creating new approaches 84 underserved and rural areas. to patient care,” said GRACE SU, MD, chief of the VAAAHS Gastroenterology The SCAN-ECHO program, funded Section and associate chief of medicine through a Veterans Health for subspecialty care and access. Administration (VHA) Healthcare Transformation Initiative (T21) Improving access to subspecialty grant, incorporates both real-time Grace Su, MD care and distance learning case consultations among remote primary care physicians and U-M As the country’s largest integrated Dr. Su led the development of, and now Gastroenterology and Hepatology health system, the veterans’ health- directs, a transformational program specialists. The program includes care system was also one of the first dubbed SCAN-ECHO (Specialty Care CLINICAL PROGRAMS
a distance learning component, About two-thirds of patients referred to disease, access to specialty care was virtual and telemedicine approaches, Through groundbreaking analyses, Dr. with educational sessions for which the VAAAHS liver clinic are patients out- associated with an improved five-year depending on their location and Su and colleagues have shown that a physicians can earn continuing side the system’s catchment area and, survival rate. The findings support the condition. number of biomarkers derived from education credit. on average, patients travel 160 miles need for innovative use of technolo- imaging provide quantifiable insights “We always let patients know we can roundtrip to be seen in Ann Arbor. gy to expand access to subspecialists. into a patient’s state (publication “Over time, by sharing treatment still help, even if travel is difficult for citations available at med.umich.edu/ strategies for specific cases and For primary care physicians in remote Screening and treating hepatitis C them,” said Dr. Su. “It might mean they surgery/morphomics). Those biomark- discussing new medical research, the and underserved areas, the program and other liver diseases—virtually have to come to Ann Arbor once for an ers include organ size and condition; primary care physicians and specialists enables them to diagnose, treat initial visit, but now we can offer them In addition to SCAN-ECHO, the VAAAHS volume and quality of particular mus- at the VAAAHS develop close working and manage patients with more several options for their long-term care uses other electronic and virtual cles and muscle groups; visceral and relationships, which only improves complex chronic diseases, gaining and management.” care delivery models. By looking at subcutaneous fat volumes, distribution care for patients,” said Dr. Su. valuable insight and expanding their 85 EMR data and patient registries, the Assessing risk and improving and density; bone shape; and certain expertise. “Since the VAAAHS serves as a ter- health system can identify and reach outcomes through morphomics vascular measures. Using morphomics, tiary care referral center for other VA The Ann Arbor SCAN-ECHO program out to patients with diagnosed but physician investigators are able to The VAAAHS’ vast repository of data health systems within a wide region, is one of the largest—and one of the untreated liver disease, linking them to predict cirrhosis and determine the supports another innovative approach including Michigan, Indiana and first—to focus specifically on hepatolo- much-needed care. best treatment option for patients who to health services research and care much of Ohio, a program like this gy subspecialty care for veterans. A go on to develop liver cancer. Patients with liver disease may be delivery—the use of analytic mor- saves many patients from costly and recent study published by Dr. Su and managed through community-based phomics to assess a patient’s current Morphomics efforts are currently inconvenient travel as they can be colleagues in the American Journal of outpatient clinics in Jackson, Flint and condition, identify risk factors and underway to assess disease activity and treated in their own communities,” Gastroenterology (2016; 111(6):838- Toledo by physicians trained by U-M tailor treatment. progression in liver, pancreatic, inflam- Dr. Su added. 44) found that, for patients with liver specialists. Other patients may opt for matory bowel and Crohn’s disease in order to personalize patient treatments and improve outcomes. “The beauty of morphomics within such a large, integrated system as the VAAAHS is that it accurately quantifies information we already have in patients’ electronic records from imaging and combines it with other clinical data,” said Dr. Su, who serves as associate director for the University of 86 Michigan Morphomics Analysis Group. “We’re putting the data to work in order Joel Rubenstein, MD, MSc to figure out how best to personalize RET), a pre-clinical tool to predict care for each patient.” whether a patient has Barrett’s Predicting esophageal adenocar- Esophagus (mberet.umms.med. cinoma in patients with Barrett’s umich.edu). It uses only a few simple Esophagus questions about symptoms of gastro- esophageal reflux and tobacco use, JOEL RUBENSTEIN, MD, MSc, has as well as measurements of waist and developed the Michigan Barrett’s hip circumference. Esophagus pREdiction Tool (M-BE-
Ann Arbor VA Hospital CLINICAL PROGRAMS
Dr. Rubenstein has received a grant clinicians can ensure that patients hepatology care at the VAAAHS create from the Department of Veterans who are likely to benefit get screened, a fertile training ground for the next Affairs to validate the accuracy of and those who are not likely to benefit generation of physicians. the tool in a population of 1,500 avoid unnecessary and costly care. patients undergoing their first upper Personalizing treatment for IBD endoscopy. He will also retrospectively apply it to a population of 100,000 AKBAR WALJEE, MD, MSc, also uses individuals who have that data avail- computers and predictive models able from the late 1960s and were to provide better decision-making followed longitudinally since then. for tailored and individualized care, The aim is to determine whether the especially in costly GI diseases and 87 tool accurately predicts which of those low-resource settings. Dr. Waljee has Sameer Saini, MD, MSc Akbar Waljee, MD, MSc individuals developed esophageal been working with colleague DR. adenocarcinoma. individual patients. These estimates RYAN STIDHAM to develop new decision support tools for physicians can be used to help physicians make to individualize treatments for patients Optimizing selection of patients tools using analytic morphomics to more individualized decisions about with inflammatory bowel disease. for colon cancer screening measure disease severity in Crohn’s cancer prevention. The estimates can patients. Using machine learning, Dr. Growth offers educational also be presented to patients who are SAMEER SAINI, MD, MSc, uses Waljee integrates the information from opportunities computer microsimulation modeling considering screening, allowing them imaging studies with laboratory and to estimate the benefits and harms to make more informed decisions medical data available in patient elec- The novel approaches to delivering of colorectal cancer screening for about their health. By implementing tronic medical records to develop better specialized gastroenterology and these data into clinical practice, 88 Education + Training EDUCATION + TRAINING
Fellows
Training the next generation of gastroenterologists and hepatologists is the primary mission Mohammed Farivar, 1975 Jean-Pierre Raufman, 1980 of the Division. The University of Michigan is recognized both for its excellent clinical Eugene Rudolph, 1975 Sami Achem, 1981 training as well as for its top ranked training in basic science, outcomes and health services Harold Tobes, 1975 Patricia Sell, 1981 research . During the last 75 years, the Division has trained more than 400 gastroenterologists Charles Balabaud, 1976 Charles Thueson, 1981 and hepatologists who are practicing in 33 states . Many of our trainees have evolved into Daniel Biery, 1976 Ferdinand Balatico, 1982 outstanding clinicians, clinical leaders and academic leaders in their own right . Berj Minasakanian, 1976 Joseph Davanzo, 1982 Peter Naus, 1976 Patricia Kuzma Sell, 1982 Gastroenterology Fellows 1st Arpan Patel, 2015-2018 Transplant Hepatology Fellows Varin Uppaputhangkule, 1976 Gary Monash, 1982 Year Shreya Sengupta, 2015-2018 Rinjal Brahmbhatt, 2016-2017 Alan C. Dopp, 1977 Herman Perman, 1982 Eric Shah, 2015-2018 Dennis Chen, 2016-2019 Dekey Lhewa, 2016-2017 Peter Hooberman, 1977 Michael Persaud, 1982 Matthew Sturm, 2015-2018 Vincent Chen, 2016-2019 Roberto Prizont, 1977 Joseph Tan, 1982 Advanced Endoscopy Fellows 89 Amar Mandalia, 2016-2019 Gastroenterology Fellows 3rd Sai Sista, 1977 Howard Wallace, 1982 Chanakyaram Reddy, 2016-2019 Year Amy Hosmer, 2016-2017 John S. Farrell, 1978 Robert Winchell, 1982 Arjun Sondhi, 2016-2019 Dmitry Shuster, 2016-2017 Safiul Hasan, 1978 Edward Clay, 1983 Paul Corsello, 2014-2017 Mary Thomson, 2016-2019 Hossein Tavassollie, 1978 Paul Giradi, 1983 Anand Jain, 2014-2017 Fellows 1954-2016 Dabo Xu, 2016-2019 Joel V. Weinstock, 1978 Gary Hills, 1983 Tossapol Kerdsirichairat, 2014- Basil Hirschowitz Nefins Barlas, 1979 Brian Liska, 1983 Gastroenterology Fellows 2nd 2017 , 1954 Donald Kuiper Mostafa Ibrahim, 1979 John Joseph Wells, 1983 Year Jenny Maratt, 2014-2017 , 1969 Bergein Overholt Timothy Nostrant, 1979 Thomas Huber, 1984 Marc Piper, 2014-2017 , 1969 Joy Chang, 2015-2018 Newell Augor John A. Schaffner, 1979 Patricia Lorusso, 1984 Anna Tavakkoli, 2014-2017 , 1970 Phillip Chisholm, 2015-2018 Eugenuis Ang Hidenori Kawanishi, 1980 Baldev Malik, 1984 Andy Wright, 2014-2017 , 1971 Anand Patel, 2015-2018 Haair Aharonian, 1975 Manus Krasman, 1980 Milton Mutchnick, 1984 Allan Coates, 1985 James Scheiman, 1987 Rosanne Murphy, 1991 Khalouck Abdrabbo, 1995 Naresh Gunaratnam, 1998 Arthur French, 1985 Peter Traber, 1987 Bahri Bilir, 1992 Rajiv Bansal, 1995 Mark Jeffries, 1998 Bruce Kovan, 1985 William Weatherhead, 1987 Kim Brown, 1992 John Carethers, 1995 Margaret Kinnard, 1998 John Persson, 1985 Andrew Welch, 1987 William Dobbins, 1992 Robert Fontana, 1995 Steven Klein, 1998 Joyce Richards, 1985 John Wiley, 1987 Ken Lown, 1992 William Grady, 1995 Uri Ladabaum, 1998 Jeffrey Sams, 1985 Friedrich Loura, 1988 Arnold Markowitz, 1992 Graeme MacDonald, 1995 Robert O’Shea, 1998 John Del Valle, 1986 Chester Zahn, 1988 David Roberts, 1992 Donn Marutani, 1995 Michelle Anderson, 1999 Gary Falk, 1986 Leslie Aldrich, 1989 Andrea Todisco, 1992 Frederick Askari, 1996 Byunki Kim, 1999 Daniel Fall, 1986 Tom Colturi, 1989 Traver Traber, 1992 Gyorgy Baffy, 1996 Partha Nandi, 1999 William Gracie, 1986 William Hasler, 1989 Gary Wu, 1992 Cary Caldwell, 1996 Shanthi Srinivasan, 1999 Robert Helft James Vanpopering Nuray Bilir Steve Carpenter Mark Stern 90 , 1986 , 1989 , 1993 , 1996 , 1999 Russell Keinath, 1986 Peter Walsh, 1989 William Chey, 1993 Robert Holmes, 1996 Adam Gorelick, 2000 H. Horchang Lee, 1986 Dale Bachwich, 1990 Michael Kochman, 1993 Srinivas Janardan, 1996 Khozema Hussain, 2000 Wilfred Lee, 1986 W. Michael McDonnell, 1990 Stephen Kuehn, 1993 Joseph Kolars, 1996 Ernest Ofori-Darko, 2000 Stanley Strasius, 1986 Gustavo Torres-Barrera, 1990 Steven Taylor, 1993 Eric Mortensen, 1996 Melissa Rich, 2000 JoAnne Wilson, 1986 Danielle Turgeon, 1990 John W. Walsh, 1993 Stephen Webster, 1996 Ezra Burstein, 2001 Rex Antinozzi, 1987 Ellen Zimmerman, 1990 Caryn Berkowitz, 1994 Sherin Koshy, 1997 Manish Chokshi, 2001 Jeffrey Barnett, 1987 Daryl Daugherty, 1991 Laurel Fisher, 1994 Mimi Takami, 1997 Matthew DiMagno, 2001 Jian-Jun Chen, 1987 John Farnen, 1991 Joseph Henderson, 1994 William Tierney, 1997 Kelvin Hornbuckle, 2001 Michael Lucey, 1987 Steve Kuehn, 1991 Tom Judge, 1994 Richard T. Wille, 1997 John C. Rabine, 2001 Joel Montbriand, 1987 James H. Morse, 1991 Ken Kohagen, 1994 Michael Yeh, 1997 John Kao, 2002 Robert Rose, 1987 Pat Mortell, 1991 Mark Sims, 1994 Michael Cannon, 1998 Mark Marilley, 2002 EDUCATION + TRAINING
Kimya Nguyen, 2002 Wei Ming Sun, 2006 April Grudell, 2010 Mina Rakoski, 2012 Jessica Mellinger, 2015 Leonard Quallich III, 2002 Hellan Kang, 2007 Akshay Gupta, 2010 Amol Rangnekar, 2012 Andrew Reinink, 2015 Thomas Shehab, 2002 Chun Hsu, 2007 Mohammed Jafri, 2010 Steven Scaglione, 2012 Andrew Shreiner, 2015 Erik-Jan Wamsteker, 2002 Nonthalee Pausawasdi, 2007 Nirmal Kaur, 2010 Benjamin Young, 2012 Graham Brady, 2016 Ali Yazdani, 2002 Ryan Taylor, 2007 Niloy Jewel Samadder, 2010 Nisa Kubiliun, 2013 Alison Freeman, 2016 Betty Kim, 2003 Michael Volk, 2007 Amit Singal, 2010 Joshua Max, 2013 Amy Hosmer, 2016 James Rhee, 2003 Mark Zeglis, 2007 Jason Taylor, 2010 Diane Nguyen, 2013 Monica Konerman, 2016 Krishnavel Chathadi, 2004 Haritha Avula, 2008 Constantinos Anastassiades, 2011 Aarti Oza Bedi, 2013 Alexander Larson, 2016 Peter Higgins, 2004 Badih Elmunzer, 2008 John Bassett, 2011 Anoop Prabhu, 2013 Andrew Nett, 2016 Mary Ann Huang, 2004 Darren Brenner, 2008 Jason Lewis, 2011 Reena Salgia, 2013 Pranith Perera, 2016 Jason Phillips Syed Abbas Fehmi Rajnish Mishra Heather Simpson Andrew Read , 2004 , 2008 , 2011 , 2013 , 2016 91 Cyrus Piraka, 2004 Robert Pompa, 2008 Michael Rajala, 2011 Yu-Ming Chang, 2014 Dmitry Shuster, 2016 Joel Rubenstein, 2004 Sameer Saini, 2008 Ryan Stidham, 2011 Neel Choksi, 2014 Marisa Spencer, 2016 Ahmed Sherif, 2004 Pratima Sharma, 2008 Shannan Tujios, 2011 Radoslav Coleski, 2014 Erin Spengler, 2016 Michael Cleary, 2005 Dahlia Awais, 2009 Julie Yang, 2011 Anthony DeBenedet, 2014 Luke Evans, 2005 Amaar Ghazale, 2009 Eugene Zolotarevsky, 2011 Shail Govani, 2014 Dave McMillen, 2005 Soojong Hong, 2009 William Cooney, 2012 Bari Khurram, 2014 Stacy Menees, 2005 Vinay Katukuri, 2009 Sharlene D’Souza, 2012 Megan Adams, 2015 Richard J. Saad, 2005 Aparna Repaka, 2009 Jennifer Jorgensen, 2012 Tannaz Guivatchian, 2015 Agata Bednarz, 2006 Akbar Waljee, 2009 Beth Manoogian, 2012 Jacob Kurlander, 2015 Taft Bhuket, 2006 Craig Womeldorph, 2009 Michelle Muza-Moons, 2012 Robert Lapp, 2015 Stephen Brackbill, 2006 Nicholas Boetticher, 2010 Darashana Punglia, 2012 Sean McCarthy, 2015 University of Michigan Gastroenterology Fellowship Program: EDUCATING THE LEADERS AND BEST
One of the largest and most highly respected gastroenterology training programs in the National Institutes of Health (NIH) United States, the University of Michigan Gastroenterology Fellowship Program is recognized Training Grants, one in Basic Science both for its clinical training as well as for its top-ranked training in basic science and outcomes Research Training and a second in research . GI Epidemiology. The U-M Training Program in GI Epidemiology is one “The volume of procedures, exposure Beyond meeting Accreditation Council • Master of Science degree in of only three such outcomes research to a breadth of experts in many sub- for Graduate Medical Education Clinical Research Design and training programs in the country. specialty areas, myriad cutting-edge training requirements, the U-M Statistical Analysis through the clinical and outcomes research Gastroenterology Fellowship Program U-M School of Public Health Currently, the U-M GI fellowship opportunities and many other offers additional, integrated training (NIH T32 DK062708) program has been able to support at factors make the three-year U-M GI via several novel programs: least two fellows through the National • Forthcoming business and 92 Fellowship Program truly stand out,” Clinician Scholars Program. The • National Clinician Scholars leadership training program, said HARI CONJEEVARAM, MD, NIH Basic Science and Translational Program leading to a Master of Business MSc, Professor of Medicine, Division Research Training Grant provides Administration degree of Gastroenterology and Hepatology • Graduate Medical Education funds to train up to three GI fellows and director of the fellowship program Scholars Program Support, mentorship and interested in basic and translational since September 2010. collaboration digestive sciences. The NIH GI • House Staff Innovation & Entre- Epidemiology and Outcomes Training H Individualized training a preneurship Program, begun The U-M Gastroenterology Fellowship r grant which support two GI fellows i C in 2015 Program is one of the only GI o Fellows’ interests, skills, educational focuses on clinical outcomes and nj ee training programs funded with the va goals and passions all drive an • Physician Scientist Training investigation with resources and tools ram support of two highly competitive , M commonly utilized, including large D, MSc individualized fellowship experience. Program (NIH T32 DK094775) EDUCATION + TRAINING
databases, cost-effective analysis, and recruited for faculty positions in meta-analysis and other health other academic institutions as well services research techniques. as private practice settings. In the past few years, 80 to 100 percent of “The amount of support that our graduating fellows have stayed in fellows receive in clinical and research academia. training, in mentorship from faculty and through a high degree of collab- Fellows’ accomplishments reflect oration with other departments and the dedication and investment of schools within the University affords GI division faculty and mentors in our trainees a truly unique fellowship integrated programs as well as the experience,” said Dr. Conjeevaram. personalized approach. 93 Demonstrating excellence and “We work hard to bring out the best in supporting success our trainees by allowing them to find their individual passions in the field, The U-M Gastroenterology Fellowship to think and to be creative,” said Dr. Program currently has 21 fellows Conjeevaram, “and we provide them (seven per year), among the largest with the best environment we can and programs in the nation. Graduates are the resources they need to find their highly sought for advanced fellowship niche and achieve their potential.” training, for example in Advanced Hepatology or Advanced Endoscopy, Training Gastroenterologists to Perform Clinical and Outcomes Research: THE NEXT STEP
Scientific discoveries in the laboratory are most helpful when findings are translated, through Healthcare Policy and Innovation or an Research and Development Center of clinical trials, into new therapies and diagnostic tools . But developing new therapies and MSc degree in Clinical Research Design Innovation) and specialized centers diagnostic tools is not enough—physicians also need to deliver these services to the right and Statistical Analysis from the School within the Institute for Healthcare patients at the right time, ensuring timely and high-quality care. As the U.S. healthcare system of Public Health. These programs focus Policy and Innovation (IHPI). changes, there is a greater focus on quality of care as opposed to quantity of care, and outcomes on outcomes research/healthcare policy “With such a breadth of faculty, and health services research informs the delivery of optimal clinical care . Such research also aids and clinical trial design, respectively. both within our Division and in the development of clinical practice guidelines and healthcare policy . Both programs provide instruction in across the University, our trainees statistics and clinical research. The Division of Gastroenterology and of the few such programs in the nation) During their fellowship, postdoctoral can find content mentors who are Hepatology is home to the Training from its inception until 2016. trainees focus on a specific research Trainees can also draw upon myriad experts in virtually any GI topic Program in GI Epidemiology, which question, such as quality improvement resources offered at U-M. In addition to while also receiving support from 94 has been funded continuously by in colorectal cancer screening with the faculty in the Division of Gastro- methodological mentors across a a National Institutes of Health T32 colonoscopy, and complete three enterology and Hepatology, training variety of disciplines,” said SAMEER training grant since 2002. core projects: a systematic review, program faculty include biostatisticians, SAINI, MD, MSc, who was promoted a secondary data analysis and a healthcare policy experts and experts to Director of the program in 2016 “The performance of clinical trials prospective study under the guidance in clinical trial design and outcomes after having served as Associate and research on healthcare delivery of a team of mentors. research. These mentors span, and offer Director from 2013-2016. is critical to improving patient care, access to resources within the School of and the first step in that process In order to complete these projects, In addition to supporting advanced Public Health, the Division of General is to train GI fellows to become GI fellows need formal training. The research training for selected fellows, Internal Medicine, the VA Center for outcomes researchers,” said PHILIP U-M is fortunate to be able to offer faculty also support the research Clinical Management Research (a na- SCHOENFELD, MD, MSEd, MSc (EPI), two options: an MS degree in Health education of our GI fellows at large. tionally recognized VA Health Services who was director of the program (one Care Policy through the Institute for Philip Schoenfeld, MD, MSEd, MSc (EPI) EDUCATION + TRAINING
PROGRAM SUCCESS AT-A-GLANCE Fourteen Dr. Saini also is leading efforts to The Training Program in GI to improve adherence to biologic GI fellows have completed the program since the develop a mentoring program for Epidemiology has a proven track agents in IBD patients, and JESSICA first trainees graduated in 2004. Among them, junior faculty interested in GI health record. Recent trainees include MELLINGER, MD, MSc, a transplant • Eleven are faculty in academic programs that offer services research careers. As Director MEGAN ADAMS, MD, JD, MSc, a hepatologist with an interest in gastroenterology fellowship programs. of the Junior Faculty to K Award (JF2K) GI health services researcher and improving outcomes in patients with Seven Program, he is leveraging Division attorney with a particular interest in alcoholic liver disease. • serve on the faculty at the University of and Internal Medicine department healthcare policy. Dr. Adams, whose Michigan. “Our former trainees are now leaders resources and the infrastructure of the work focuses on factors driving use in GI outcomes and health services • Four of the first five graduates hold the rank of IHPI to build an efficient pathway to of monitored anesthesia care, was research and mentors in their own Associate Professor of Medicine with tenure. career development funding, crucial recently appointed Chair-Elect of the right, fostering the growth of the next to junior faculty for securing protected AGA Quality Measures Committee. In • Nine have successfully applied for Career generation of researchers who will 95 research time and funding additional this role, she will have the opportu- Development Awards from NIH, VA, AASLD and AGA. develop new approaches to patient Sameer Saini, MD, MSc training. The JF2K Program, in its first nity to shape the direction of quality care while revising clinical practice • Seven have completed their Career Development Since 2013, Dr. Saini has led the year, will serve as a model for other measure development in gastroen- guidelines and reshaping healthcare Award funding, and these physicians are principal GI Clinical Research Conference, a medicine subspecialties developing terology and work with payers and policy,” said Dr. Saini. investigators on a total of three RO1s, three VA Merit monthly conference for fellows where health services research programs. policymakers on matters related to Awards and two large U.S. Department of Defense ongoing research is presented and quality of care. grants, as well as multiple small federal grants for discussed in an interactive format. “Our goal is to excite GI fellows about Other recent graduates include pilot research. In 2016, Dr. Saini was awarded the clinical, outcomes and health services SHAIL GOVANI, MD, MSc, an Fellows Teaching Award for his role in research and guide them into success- • Graduates have numerous first-author publications inflammatory bowel disease (IBD) leading the conference series. ful academic careers with independent in top journals for clinical and outcomes research, funding,” said Dr. Saini. specialist who is examining ways including the New England Journal of Medicine, JAMA, BMJ, Gastroenterology, American Journal of Gastroenterology, Gut and Hepatology. Legacy of Achievement FELLOWSHIP TRAINING IN TRANSPLANT HEPATOLOGY
The Division of Gastroenterology and Hepatology offers one of the longest-standing and most well-respected Transplant Hepatology fellowships in the country . The 12-month training program, accredited by the American Board of Internal Medicine (ABIM) in 2007, follows the Division’s three-year GI fellowship and accepts two fellows each year. Those two spots consistently fill given the fellowship’s popularity, noted ROBERT J. FONTANA, MD, Medical Director of the Fellowship Program .
The fellowship program has built SCAGLIONE (2011) completed liver failure (ALF) and organ donation a consistent track record by any studies on hepatocellular carcinoma with Dr. Fontana while at U-M. He is number of measures. Since its (HCC) and transplant outcomes now Associate Professor of Medicine 96 inception, six fellows have received during his fellowship training. He at the University of Kansas liver the highly competitive Transplant is now a transplant hepatologist at transplant program and continuing Hepatology Fellowship Award from Loyola University and training other to conduct studies on ALF and viral the American Association for the GI fellows and hepatologists as well hepatitis. Study of Liver Diseases, and the pass as pursuing research projects in fatty DR. AMIT SINGAL (2010) completed rate on ABIM board examinations has liver disease. several database projects as well as been 100 percent. DR. RYAN TAYLOR (2006) was studies of serum biomarkers of liver But the greatest legacy of the awarded the AASLD Transplant cancer during his fellowship at U-M. fellowship, according to Dr. Fontana, Hepatology fellowship and After joining the faculty at University is what trainees go on to do after completed a master’s degree in of Texas Southwestern Medical graduating. For example, DR. STEVE clinical research and studies on acute Center, he has accrued extensive EDUCATION + TRAINING
grant funding and research awards to DRS. MOHAMMED JAFRI (2010), Behind the fellows’ success is a team further study the epidemiology and RINA SALGIA (2014), JOHN of dedicated hepatologists who causes of liver cancer. BASSETT (2010) and SHANNON are recognized nationally for their TUJIOS (2010) have gone on to contributions to research, training After obtaining her master’s degree become teachers and leaders in and clinical care of patients with in clinical research, DR. MINA other major liver centers around the advanced liver disease. RAKOSKI (2012) pursued studies in country, disseminating the expertise palliative care during her transplant “What drives our program is the they gained at U-M. hepatology fellowship and assumed caliber of our fellows and of our a faculty role after graduation. That expertise comes from rigorous faculty, whose goal is to offer the training. Fellows hold their own best possible training on a consistent As a transplant fellow, DR. JESSICA weekly hepatology and transplant basis,” said Dr. Fontana. “The fruits 97 MELLINGER (2014) completed clinics where, with direct supervision of those efforts are graduates who studies in alcoholic liver disease from faculty, they learn how to establish their own successful and access to care. Since joining diagnose and treat patients with careers, contribute to research and the faculty in 2014, Dr. Mellinger acute and chronic liver disease. In improve outcomes for patients with was awarded the highly competitive addition to rotations through the liver disease both here and around Sheila Sherlock award from the inpatient service, pathology and the country.” AASLD as she prepares for her Robert J . Fontana, MD Jessica Mellinger, MD, MSc pediatrics, fellows also complete at K-award funding. least one academic research project that they publish or present at a scientific meeting. Developing Expertise in Advanced Endoscopy
Advanced endoscopic procedures, including endoscopic ultrasound (EUS) and endoscopic leaders in endoscopy research and retrograde cholangiopancreatography (ERCP), are critical to the diagnosis and treatment of practice, including Drs. Michael many gastrointestinal disorders, and they require a high level of clinician skill . To prepare Kochman, Uri Ladabaum and Joe trainees, the Division offers a fourth year, 12-month Advanced Endoscopy Fellowship to Elmnuzer, and a long list of others. physicians who have completed a three-year Gastroenterology fellowship . Our Fourth-year fellows have “It’s an unusual training program eight faculty have extensive surgeons, attend a broad array contributed research on the role in that our faculty provide fellows experience with EUS and ERCP. The of conferences and are expected of endoscopy in pancreatic cyst with a broad perspective and program performs approximately to make their own research management as well as chronic any number of opportunities, 1,500 procedures annually, contributions. pancreatitis and endoscopic both from the procedural and giving trainees significant clinical techniques for complex polypectomy. “Here at U-M,” Dr. Scheiman said, “we 98 intellectual standpoints,” said opportunities. Trainees also gain not only train our fellows to perform JAMES SCHEIMAN, MD, director exposure to state-of-the-art stenting these complex procedures; we of the program. Dr. Scheiman is and mucosal resection and ablation continually and critically assess the also involved nationally in efforts techniques as well as balloon- literature and apply it to improving to assess ERCP quality and how assisted enteroscopy. the care of our patients.” both trainees and experienced Another distinguishing feature of practitioners alike can improve skills The Division has had a formal the program is its scholarly focus. and outcomes. fellowship since 2008, 17 trainees, Fellows run a dedicated, bi-weekly 12 in academic practice. Prior to The University of Michigan Advanced case conference in collaboration formal fellowship senior members Endoscopy Fellowship program’s with active faculty and hepatobiliary of the group have mentored many JAMES M. SCHEIMAN, MD ENDOSCOPIC ULTRASOUND PROGRAM
The endoscopic Ultrasound (EUS) program, started in 1993, has grown from the first providers of this major endoscopic innovation in the State of Michigan to an internationally recognized program of excellence in clinical care, teaching and research . EUS revolutionized the care of patients with known or suspected GI malignancy, 99 particularly of the pancreas, dramatically changing the diagnostic landscape for patients with pancreatic neuroendocrine tumors as well as adenocarcinoma . The program pioneered the use of EUS in minimally invasive therapeutic applications . The majority of advanced endoscopists in the region as well as many leaders in endoscopic research and clinical care trace their roots to the University of Michigan EUS training program .
Illustration: Bill Burgard IBD Training: PREPARING TRAINEES FOR THE COMPLEX DEMANDS OF TERTIARY IBD CARE
As recent discoveries have advanced the understanding and treatment of inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, “the management of IBD has become much more complex,” said JAMI KINNUCAN, MD, a specialist focusing on IBD education . “This increasing complexity demands additional training for our fellows ”. Dr. Kinnucan has created a new IBD and research interests in IBD. The U-M, under the direction of PETER training curriculum for the Division’s curriculum focuses on outpatient HIGGINS, MD, PhD, MSC, and other categorical fellows that focuses on the management, endoscopic assessment senior IBD faculty. And other graduates multidisciplinary management of IBD and management and postoperative have joined academic medical centers patients. Fellows rotate on the inpatient care of IBD patients as well as scholarly throughout the country. service, manage postoperative IBD contributions. “What makes our program unique is 100 patients and participate in outpatient “Tertiary care of patients with IBD that our categorical Gastroenterology continuity clinics. They are actively in- requires a trainee to focus their clinical fellows are able to personalize their volved in multidisciplinary conferences, training to maximize exposure to this training to acquire the knowledge and a monthly IBD journal club and weekly complex disease state,” said Kinnucan. experience they will need in practice IBD radiology teaching rounds. “Our curriculum not only incorporates to care for their patients with IBD,” Peter Higgins, MD, PhD, MSc In addition, Dr. Kinnucan and two current literature but also addresses said Dr. Kinnucan. “For me, the ability current categorical fellows, DR. PAUL many of the gaps in IBD training that to watch trainee physicians build CORSELLO and DR. ANAND PATEL, fellows nationally have identified.” their knowledge to manage complex J are piloting an IBD Core Training patients on their own is incredibly am Many trainees in the program i Kin Curriculum for fellows with clinical rewarding.” nuc have gone on to become faculty at an, MD EDUCATION + TRAINING
Roadmap to Leadership: NEW PROGRAM TO TRAIN FELLOWS IN BUSINESS AND POLICY ASPECTS OF GI
Throughout its 75-year history, faculty in the University of Michigan Division of careers, but they aren’t sure how to The GI division’s program will be Gastroenterology and Hepatology have provided strong leadership—guiding professional break into those circles.” one of the only, if not the only, GI societies, serving as editors of major journals, helping to shape healthcare policy . fellowship program to make business The new program, tentatively named and professional leadership an “Currently, no real roadmap exists to Now on the U-M GI faculty, Dr. Allen “Life, Leadership and Legacy” and integral part of traditional fellowship help young physicians—in community is working on a novel program to scheduled to begin in mid-2017, training. practice or academia—learn how help fellowship trainees gain the will educate interested fellows to progress up the ladder to lead knowledge and experience to chart in career planning, financial and “Not many places have the organizations, including medical their course toward professional practice management, organizational capabilities that U-M does to create a practices,” said JOHN ALLEN, MD, leadership. leadership and healthcare policy. program such as this,” said Dr. Allen, MBA, professor of medicine. who will leverage those capabilities “In talking with fellows all over the The program will draw upon the for an important purpose: “We plan 101 Dr. Allen himself has held many country, one of the things they’ve University’s wealth of resources and to make the University of Michigan leadership roles in the past; he identified as missing from their expertise in many disciplines as well the place for training future GI was president of the American training is information about how to as from from external professionals, leaders.” Gastroenterological Association run the business aspects of their lives including policymakers and leaders John Allen, MD, MBA and also served as clinical chief of and careers—be it job searches, start- of large GI practices. digestive diseases at Yale University. ing a community-based ambulatory Such broad and deep expertise Trainees in fellowship programs He helped establish a large, single- surgery center or running a successful will enable a flexible, highly around the country may be inspired specialty GI practice in Minnesota laboratory or clinical research program individualized approach, giving by these GI leaders, but many aren’t with more than 60 physicians, and in academia,” he said. “They know fellows options to pursue further sure how they themselves might developed its nationally recognized they need to make informed decisions training in specific areas of interest. advance to serve in similar ways. quality program. about where they want to take their Basic and translational research is a major mission of the Division. Physi- cian scientists, clinical investigators and master clinicians work together seamlessly to ensure that many basic science observations are translated into clinical applications. For example, the discovery of a trypsin-sensitive CCK releasing factor, Basic, Clinical + which stimulates CCK release, provided 102 the basis for understanding the clinical utility of pancreatic enzyme supple- Translational Research ment in alleviating pain in chronic pancreatitis. The observation that somatostatin has both excitatory and inhibitory actions in myenteric choliner- gic transmission and thus, plays a critical role in mediating both limbs of the peristaltic reflex, led to the use of Octreotide in the treatment of chronic intestinal pseudoobstruction. Embracing Practice Through Discovery
The GI Peptide Center (P30 DK034933) In addition to multiple National been funded for 10 years and was re- for the early detection of precancerous our physicians based at the VA have is the epicenter of the Division’s re- Institutes of Health (NIH) R01, U01, newed in 2013 for another five years. or cancerous lesions. Currently the tech- received multiple VA Merit and Career search enterprise. Funded since 1984, and K08/K23 grants, the Division nique shows promising applications for Development Awards. The second Program Project was initi- the Center today has 58 primary inves- currently has two major Program early detection of Barrett’s Esophagus ated by DR. THOMAS WANG in 2011. Clinical Investigation is a major focus tigators and four major Service Cores Projects through NIH P01/U54 and early colonic neoplastic changes This GI Molecular Imaging Program of our research enterprise. In 2016 the to support GI research related to signal mechanisms. In 2002, DR. JUANITA in patients with inflammatory bowel was funded by the National Cancer In- Division had 13 foundation grants, 12 transduction mechanisms governing MERCHANT in collaboration with DR. disease. His team includes DRS. JOEL stitute (NCI) through U54 mechanisms investigator-initiated pharmaceutical homeostasis and GI disorders. The DEB GUMUCIO (Department of Cell RUBENSTEIN, ELENA STOFFEL and (U54 CA163059). Using peptides as studies, and 84 clinical trials. The com- approach includes studies on genetics and Developmental Biology), DR. KIM TURGEON and is supported by a a novel probe platform, Dr. Wang has bined total of all grants in the Division and gene regulation, cellular signaling LINDA SAMUELSON (Department of group of dedicated study coordinators developed imaging agents with high is 167, totaling $16 million of annual pathways, receptors and ion channels. Molecular and Integrative Physiology) led by ELAINE BRADY. The total NCI specificity and binding affinity to over- funding, making our Division one of 103 Research themes include: 1) Neurobi- and DR. ANDREA TODISCO (Division funding amounts to $11.8 million over express or gene-amplified targets on the most highly funded GI divisions in ology of visceral pain, enteric motility of Gastroenterology and Hepatology) five years. the surface of cancer and precancerous the country. and appetite control; 2) Molecular and successfully initiated a Program cell types. During endoscopy these The Division takes pride in the fact cellular mechanisms of gut inflamma- Project P01 DK062041 to investigate Our rich tradition of basic and clinical peptide probes can be fluorescently that 44 percent of its 75 faculty are tion; and 3) Cell growth, differentiation cellular decisions in the GI tract. The research enhances our clinical practice labeled and applied in high concen- Physician Scientists. Most of the and programmed cell death. The Center underlying theme focuses on the with innovative approaches and tration to the mucosa for detection by research is funded through NIH/NCI or currently has a research base of $26.8 interplay between developmental new treatments for patient care. Our dual-axis confocal microendoscopy. the U.S. Department of Veterans Affairs million in digestive disease-related signaling pathways and environmen- physicians embrace practice through (VA) system. Currently the Division funding representing nearly 10 percent tal cues to direct cell specifications, In this way, Dr. Wang and colleagues discovery. has 15 R01/R37 grants, 7 U01/U54, 3 of the total research base of the Univer- homeostasis and metaplasia, a can perform real time “optical biopsies” P01/P30, and 6 K08/K23 grants, and sity of Michigan Medical School. pre-neoplastic change. This grant has Discovery and Scientific Achievement: MICHIGAN GASTROINTESTINAL PEPTIDE RESEARCH CENTER
TACHI YAMADA, MD, and CHUNG OWYANG, MD, established the Michigan Gastrointestinal Peptide 1991; 325: 1461-71). It was the first Research Center (MGPRC) and National Institutes of Health/National Institute of Digestive instance where a peptide was used to and Diabetes and Kidney Diseases-funded Silvio O . Conte Digestive Diseases Research treat a GI disorder. Center in 1984. MGPRC is the only center in the nation devoted to the study of GI peptides in the pathophysiology, diagnosis and treatment of GI disorders. Work in the Center has Dr. Owyang’s laboratory also yielded a number of seminal findings over the years, which have been translated into new characterized a new peptide, CCK- treatment approaches and improved outcomes for patients . releasing peptide, which is secreted into the intestinal lumen in response “Since its founding, the MGPRC has of glycine extended processing peptide hormone precursors may to food and stimulates CCK release. been the engine that drives our intermediates of gastrin. This have unique functions separate and Pancreatic enzymes subsequently research initiative,” said Dr. Owyang, seminal work provided the tools distinct from their end products. secreted into the lumen inactivate 104 H. Marvin Pollard Professor and for examination of substrate CCK-releasing peptide, thereby With support of the MGPRC, Dr. Division chief since 1990. “It’s the specificity of the carboxyl terminal creating a feedback regulating loop Owyang’s lab discovered that heart and soul of our translational amidation reaction, which is of (Proceedings of the National Academy somatostatin both excites and research enterprise in many ways.” critical importance in the biological of Sciences, 1996; 93: 7927-32). This inhibits myenteric cholinergic activation of nearly 50 percent of novel observation provided the basis Dr. Yamada, who served as transmission and plays a crucial all peptide hormones known today for understanding the clinical utility Division chief from 1983 to 1990, role in mediating both limbs of the (Science, 1994; 265: 440-442). of pancreatic enzyme supplements was the first to apply molecular peristaltic reflex. This led to the use in alleviating pain in chronic biology techniques to the study of Dr. Yamada went on to characterize of somatostatin to treat small bowel Ta ch pancreatitis patients by diminishing i Y biochemistry and physiology of gut specific receptors for glycine bacterial overgrowth in patients with am CCK-mediated stimulation. ad hormones. A major breakthrough extended gastrin, providing the chronic intestinal pseudo obstruction a, M D, KBE was his isolation and characterization first insight into the possibility that (New England Journal of Medicine, BASIC, CLINICAL + TRANSLATIONAL RESEARCH
This set the foundation for subsequent studies on colon cancer genetics. More recently, using a large, prospectively identified cohort of patients with acute liver failure, BISHR OMARY, MD, PhD, identified keratin 8/18 as important susceptibility genes for acute liver failure development. His studies demonstrated that ethnicity-selective 105 Richard C . Boland, MD keratin variants predisposed carriers Nobu Kamada, PhD In 1995, RICHARD C. BOLAND, MD, to death or the need for liver The groundbreaking work of NOBU uncovered the role of DNA mismatch transplantation when these subjects KAMADA, PhD, and GABRIEL repair in regulating the G2/s cell develop acute liver failure, raising NUNEZ, MD, has shown that cycle checkpoint and predicted that the possibility of using K8/K18 a host’s immune system and colon cancer with microsatellite variants as prognostic biomarkers. commensal bacteria work together instability would be resistant to Collectively, these findings provided to control enteric pathogen Cancer Research a unique link of the cytoskeleton to chemotherapy ( , infections. Their research finds that D Gastroenterology M 1995; Sep 1;55(17):3721-5). liver failure ( , 2010; mouse-pathogenic E. coli Citrobacter g, yan 139: 828-835). rodentium employs its virulence Ow Chung microbes for nutrients (Science, A second major project in the 2012; 336(6086):1325-9; Cell Host Merchant laboratory has identified Microbe, 2015; 17(5):617-27). a novel mechanism for Men1- dependent neuroendocrine tumors. JUANITA MERCHANT, MD, PhD, Dr. Merchant’s lab is the first to clarifies the mechanisms by which develop a mouse model of gastric Helicobacter pylori infection causes carcinoid tumors (Gut, 2016; 0:1–10. gastric metaplasia and cancer, by doi:10.1136/gutjnl-2015-310928). showing that dying parietal cells release Sonic Hedgehog, recruiting ELIZABETH SPELIOTES, MD, PhD, inflammatory cells that over time utilized human population-based 106 become immunosuppressive. The and functional genetic studies and Gabriel Nunez, MD Hedgehog-dependent immune showed that genetic etiology of Elizabeth Speliotes, MD, PhD, MPH cells create a pre-neoplastic obesity and nonalcoholic fatty liver factors to find a location within the affect lipid and glucose metabolism microenvironment in the stomach. disease (NAFLD) are influenced by epithelial niche in order to evade predispose to development of NAFLD. Molecular signatures from these genes in the nervous system, in commensal bacteria. In response, Dr. Speliotes’ studies provide new myeloid-derived suppressor cells adipose tissue and in the liver. Her the host develops specialized IgG to insights into the pathophysiology (Schlafens) are being tested as laboratory found that genes play a neutralize these virulence factors. of these disorders and identify new B potential biomarkers in patients role in neuronal processes, energy Nature i This process forces the pathogens targets for therapy. ( , 2015; sh infected with Helicobacter pylori. expenditure, eating behavior and r O Feb 12;518(7538):197-206; PLoS m to relocate from the epithelial niche ar predispose to development of overall Genetics y, M to the intestinal lumen, where they , 2011; Mar;7(3):e1001324). D, obesity, whereas pathways that PhD are outcompeted by commensal BASIC, CLINICAL + TRANSLATIONAL RESEARCH
to premalignant lesions such technologies offers a new toolkit for as Barrett’s Esophagus (Science scientists to study human epithelial Translational Medicine, 2013; development, homeostasis and 5:184rab1) and colorectal cancer disease in vitro. (Nature Medicine, 2008; 14:454- Over the Center’s three-decade 58). This novel methodology uses history, research has shown that endoscopy to target disease in the many gut peptides in fact extend premalignant stage to reduce the beyond their classical role as incidence, morbidity and mortality of hormones to also act as paracrine esophageal and other cancers. effectors, neurotransmitters, growth JASON SPENCE, PhD, and his lab factors and cytokines. Hence, in 107 Thomas Wang, MD, PhD are on the forefront of generating Jason Spence, PhD 2014, we changed the name of the 3D models from pluripotent stem Center to the University of Michigan THOMAS WANG, MD, PhD, biology of epithelium and disease cells. He described a human Center for Gastrointestinal Research earned his PhD in biomedical (eLife, 2016; Sep 28;5. pii: e19732. intestinal organoid model during (UMCGR) to more accurately reflect engineering, pioneered the use doi: 10.7554/eLife.19732). One his postdoctoral studies, is involved its comprehensive mission. of fluorescence-labeled peptides year after Dr. Spence arrived at in efforts to generate additional 3D for the early detection of cancer in U-M, the GI Division committed models (Stem Cell Reports, 2015; D the GI tract. He developed peptide $100,000 to develop the Organoid/ h , P Jun 3. pii: S2213-6711(15)00122- D probes by screening for high-affinity Enteroid Modeling Program for the M t, 8) and has implemented these an ligands that bind preferentially Center. This paradigm shifting set of rch models to study developmental Me Juanita Cell growth, proliferation and programmed cell death In its current configuration, the Impact overarching goal of the Center is to investigate signal trans- Today, the Center includes 58 Genetic duction mechanisms regulating primary investigators, four major + Gene Regulation homeostasis and GI disorders. research service cores and a Our approach includes studies number of educational programs on genetics and gene regula- including symposia and the tion, cellular signaling pathways, Yamada Lectureship. The Center receptors and ion channels . The also encourages and supports new areas of related research and talent Receptors + approach will be utilized by the Signaling development through pilot project 108 Neurobiology of obesity, pain and motilityPathways Ion Channels three major research themes re- flecting the common research in- funding. terests of numerous investigators The impact of the Center’s focus affiliated with the Center. Our cannot be overstated. Funding for Mechanisms of Inflammation research themes include 1) Neu- research related to this Digestive robiology of visceral pain, enteric Disease Center, currently $26.8 motility and appetite control, 2) million in digestive disease-related Molecular and cellular mecha- funding (48 percent from NIDDK) nisms of gut inflammation and 3) and $16.6 million in other research Protein Localization Microbiome + In Vivo + Cell growth, Differentiation and grant support, represents nearly 10 Molecular Biology Identification + Metabolomics Human Studies Programmed Cell Death . percent of the total research base of Folding BASIC, CLINICAL + TRANSLATIONAL RESEARCH
the University of Michigan Medical R21, R03, R00, 2 U01, U19 and 11 School. In addition, significant R01s) totaling $18,132,140 in direct institutional support ($1 million) costs ($27,142,287 total costs); a has been amassed to support 17-fold return on investment. Center objectives. It has broadened Continuously funded for over 30 the research scope of individual years, The University of Michigan laboratories and greatly expanded Center for Gastrointestinal Research, interest in digestive disease-related in short, has become the fulcrum research. Center investigators have of activity that galvanizes the been extremely productive during efforts of the large and established the last five-year funding period, group of investigators involved in 109 contributing 519 publications as a gastrointestinal research that exists result of the core services provided at the University of Michigan. through the UMCGR. Additionally, as a testament to the Center’s Pilot and Feasibility program’s success, for the past 10 years projects representing a total investment of $1,050,000 in direct costs, ($1,577,500 total costs) have generated 20 NIH awards (2 K08, 2 Host Microbiome Initiative: UNDERSTANDING THE ROLE OF GUT MICROBIOTA IN HEALTH AND DISEASE
In 2013, the University of Michigan Medical Center developed the Host Microbiome Initiative plantation (mBio, 2014; 5(3):e00893- (HMI) under the co-directorship of DRS. VINCENT YOUNG and HARRY MOBLEY . This initiative has 14). Dr. Young also used untargeted played a significant role in supporting GI faculty who are investigating host microbiome metabolomics analysis in a mouse interactions in health and GI disorders to further promote research on the role of microbiome model of C. diff. infection to show that in IBD, IBS and metabolic disorders. The Center for Gastrointestinal Research developed antibiotic-induced loss of colonization a Microbiome and Metabolics CORE . With this support, a number of divisional faculty are resistance against C. diff. was associated making important discoveries in the diagnosis, treatment and management of a number of with relative increases in primary bile gastrointestinal disorders . acids and a corresponding decrease in secondary bile acids, an environment “The Host Microbiome Initiative is an scientific and clinical investiga- in Infectious Disease have established a that favors C. diff. germination and incredible resource for the Division’s tors—and for other investigators clinical protocol using fecal microbiota increases disease susceptibility after 110 across campus,” said JOHN KAO, transplantation in treating patients antibiotic treatment (Nature Communi- MD, associate professor and gut with recurrent Clostridium difficile (C. cations, 2014; 5:3114). microbiome investigator in the HMI. diff) infection (American Journal of “The HMI has the expertise to perform Gastroenterology, 2014; 109:1065- The dynamic interaction of a pathogen comprehensive analysis of microbial 1071. The U-M was one of the first with the resident gut microbiota was communities, which enables us to institutions in the country to perform investigated by NOBU KAMADA, study the function of gut microbiota in these transplants under FDA protocol. PhD, a research faculty member in health and disease.” the Division. Dr. Kamada proposes Extending the work, VINCE YOUNG, that competition between resident The HMI serves as a hub of MD, PhD, co-director of the HMI, has microbes and pathogens is influenced microbiome-related research for published findings related to recovery by the expression of virulence Division faculty. Dr. Kao and colleagues of the gut microbiome following trans- factors by pathogens and by the John Kao, MD
Gram stain of mouse ileum showing the interface between intestinal epithelium and gut microbiota .
Photo: Kathryn Eaton BASIC, CLINICAL + TRANSLATIONAL RESEARCH
sion of beneficial probiotic species ongoing project to identify differences (NAFLD)/non-alcoholic steatohepatitis patients who develop recurrences. The (Gastroenterology, 2014; 146(2): in gut microbiota in healthy subjects (NASH), a condition increasing in findings and subsequent work may 484-496). In another study, Dr. Kao and in IBS patients following either a prevalence globally. He is also looking inform new probiotic-based therapies is identifying biomarkers that signal meat- or plant-based diet. Studies will into the role of fecal microbiome trans- to lessen the risk of complications from dysbiosis (Gastroenterology, 2015; be conducted in Beijing and Ann Arbor plantation (FMT) in the management recurring flares and infection. 149 (7): 1849-1859). to understand the impacts of diet and of NASH. Part of this work is currently in “The HMI is critical to the Division’s racial factors on the gut microbiota of collaboration with investigators at the The two also are investigating the research,” said Dr. Kao. “Not only does IBS patients. All India Institute of Medical Sciences role of the microbiome in models of the HMI make us more competitive (AIIMS) in New Delhi, India, where stress-induced hypersensitivity—akin to Additional research into the relation- in securing funding because of the there has been a rise in prevalence IBS in humans—in mice (Gastroenter- ship between the microbiome and IBS unparalleled expertise it provides us as of NAFLD, and the pathophysiology, ology, 2013; 144(7): 1478-1487). The include studies by WILLIAM D. CHEY, investigators; it also supports import- 111 including the role of diet, might differ Vince Young, MD, PhD researchers found that stress changes MD, and SHANTI ESWARAN, MD, to ant work that leads us to new ways of from that seen in Americans. nutritional requirements of both the composition of gut bacteria and characterize patient microbiota and the improving the health of our patients.” populations (Science, 2012; Jun that the microbiome indeed plays a impact of a low-FODMAP diet. In patients with ulcerative colitis (UC), ELENA STOFFEL, MD, MPH PETER HIGGINS, MD, PhD, MSc 8;336(6086):1325-9). functional role in causing symptoms, , is , is including inflammation in the colon, in examining the microbiome in families looking at the microbiome at the time Dr. Kao and CHUNG OWYANG, MD, stressed animals. with familial polyposis to try to identify of UC flares, during C. diff infection are investigating how the antibiotic communities associated with more vs. and after recovery from C. diff infection In a collaborative research effort rifaximin, recently approved for less severe polyposis. to learn whether recovery of micro- between U-M and Peking Univer- patients with irritable bowel syn- bial diversity might predict whether sity through the Joint Institute for HARI CONJEEVARAM, MD, MSc, is drome (IBS) with diarrhea, affects the patients will develop a recurrence of C. Translational and Clinical Research, looking at the role of the microbiome microbiome following treatment in diff infection or UC flare and to identify Drs. Owyang and Kao are leading an in non-alcoholic fatty liver disease rat models, including the expan- which species are present or absent in Organogenesis: GENERATING NEW HUMAN MODELS OF ORGAN DEVELOPMENT AND DISEASE
Gastrointestinal organoids, or complex, three-dimensional GI tissues derived from human and The laboratory has focused recent induced pluripotent stem cells, are providing new and invaluable insights into human organ efforts on understanding how different development and disease pathogenesis. Such insights may one day lead to more personalized regions of the intestine gain their approaches to medical treatment . identity during embryonic develop- ment and how the intestine becomes “Organoids represent a unique tool in neous and often represent only one In addition, Spence also demonstrated mature and fully functional. “This type our experimental toolbox,” said JASON type of cell, organoids represent some a process to direct the differentiation of information is critical to using these SPENCE, PhD, associate professor in of the complexity of the organ from of human pluripotent stem cells into systems in the appropriate way—we the departments of Internal Medi- which they were derived. Human in- intestinal tissue in vitro (Nature, 2011; have to match the correct organoid sys- cine, Gastroenterology and Cell and testinal organoids (HIOs), for example, 470: 105-109). The resulting HIOs tem to the correct scientific question,” Developmental Biology. “They can yield possess multiple cell types, including contained all major cell types, as well as Spence noted. 112 a tremendous amount of informa- stem cells and differentiated cell types— a mesenchymal layer that simultane- Jason Spence, PhD tion when used as models to study Paneth, goblet, enteroendocrine cells ously developed with the epithelium. Given their uses for discovery and human disease in vitro, and they are a and enterocytes. translational research, organoids help Building on that work, the Spence platform that enables new translational investigators move beyond modeling The Spence Laboratory uses organoids Laboratory has recently shown that research.” health and disease in animals to study- grown from the stem cells of patient pluripotent stem cell-derived HIOs are ing human health and disease in hu- Unlike many traditional cell lines that tissue (Stem Cell Reports, 2015; Jun similar to the immature, fetal small man tissue. “Models such as organoids have been derived from cancer, organ- 3: (15) 00122-8) taken during biopsy, intestine, specifically the duodenum, bring together basic scientists asking oids represent a renewable source of which provides opportunities to study and that when transplanted into mice fundamental biological questions with healthy tissue. And while typical cell both healthy and diseased tissues from they mature into adult-like tissue (Stem clinical scientists who are interested culture lines are relatively homoge- adult humans. Cell Reports, 2015). in understanding disease,” said BASIC, CLINICAL + TRANSLATIONAL RESEARCH
Spence, who co-authored the textbook gut, and how to treat these infections, “Basic and clinical scientists both Translational Research and Discovery can be conducted rapidly, thereby want to apply the same tool to answer in Gastroenterology: Organogenesis to quickly advancing new treatments. different questions, and the scientific Disease (Wiley, 2014). overlap creates natural synergies,” In DR. PETER HIGGINS’ lab, his team Spence said. “The strong commitment Some of those questions relate to studies the scarring and fibrosis in in- to both clinical and basic sciences, and Clostridium difficile (C. diff.), an flammatory bowel disease that causes the breadth and depth of expertise at epidemic infection in U.S. hospitals. It bowel damage and requires surgery in the University of Michigan, make it infects the colon and can cause death three quarters of patients with Crohn’s an ideal place to conduct this kind of in up to 7 percent of elderly patients. disease. Dr. Higgins’ group has been translational research.” New therapies, including blocking an- able to identify the pathways that tibodies and new antibiotics are being cause intestinal fibrosis in organoids 113 developed to fight this infection. C. and can mimic the fibrotic process that diff. bacteria can be microinjected into occurs in human intestines. With this human gut organoids to reproduce the gut organoid fibrosis system, they can infection in the lab. In organoids, the test new anti-fibrotic medications on infection breaks down the ability of the human gut organoids. Early successes gut lining to maintain barrier function with this approach are encouraging and allows invasion between epithelial as a method to develop and test new cells. With the use of organoids, labo- therapies for gastrointestinal diseases ratory experiments to understand how and rapidly determine if they work in infections such as C. diff. invade the human tissues.
Peter Higgins, MD, PhD, MSc Human intestinal organoids used to identify targets for anti-fibrotic drug development Physician-Scientists: ADVANCING BASIC SCIENCE RESEARCH AND DISCOVERY
The University of Michigan Gastroenterology Fellowship Program helps trainees develop for a productive career in Investigating the Mechanisms both the clinical and research skills that prepare them for careers in academic medicine . academic medicine . The Regulating Epithelial Cell Growth and Fellows choose from one of two tracks, Clinical or Basic Science, both of which fulfill ACGME Differentiation in the GI Tract requirements . mentoring and individual ANDREA TODISCO, MD attention that I received (Fellowship 1991) Fellows selecting the Basic Science six-year training is dedicated to syndrome. His laboratory has identi- Professor, Internal Medicine Track will be supported by a National National Institutes of Health-funded fied specific changes in the regulation played a pivotal role in my University of Michigan Institutes of Health (NIH) T32 grant research. Currently, about 40 percent of ion channels located on the sensory career development as an dedicated to training fellows in basic of the Division’s faculty are physician- nerves that transmit pain signals from investigator, educator and Dr. Todisco has a longstanding interest and translational digestive sciences scientists. Some examples of our the colon in diabetic rodent models, in research administrator ”. in the elucidation of the mechanisms (T32 DK094775). They will spend time trainees and their work include: aged animals and models of chronic that regulate epithelial cell growth 114 in Division laboratories, conducting stress. His recent research focuses Understanding the role of visceral and differentiation in the luminal basic science and translational on the role of epigenetic regulatory sensation in functional GI disorders gastrointestinal tract. In particular, his research. Many of the Division’s pathways in chronic stress-associated JOHN W. WILEY, MD investigations have been focused on Basic Science fellows are part of the enhanced abdominal pain. Dr. Wiley’s the intracellular signal transduction (Fellowship 1984) Physician Scientist Training Program research has been continuously fund- pathways that mediate the multiple, Professor, Internal Medicine (MD-PhD), in which they undertake ed by the NIH for more than 25 years. complex actions of growth factors and University of Michigan accelerated training in Internal morphogens such as gastrin, epidermal “The clinical and basic Medicine for two years, followed by Dr. Wiley’s research focuses on pain growth factor (EGF), Sonic Hedgehog ACGME-required training in clinical pathways that innervate the gut and research training I received (Shh) and the bone morphogenetic gastroenterology for a minimum of how these pathways are altered in at the University of proteins (BMPs) in the stomach. His 18 months. The remainder of fellows’ diabetes mellitus and irritable bowel most recent investigations, centered Michigan positioned me John W . Wiley, MD BASIC, CLINICAL + TRANSLATIONAL RESEARCH
on the role of BMP signaling in gastric stimulating and nourishing Investigating metabolic interactions Dr. Wu is also directing a project rewards and opportunities inflammation and carcinogenesis, environment . Without the between gut microbiota and host investigating the impact of diet on the in pursuing a career as a have involved the use of both primary GARY D. WU, MD (Fellowship 1992) composition of the gut microbiome support and the teaching physician-scientist but also cultures of gastric epithelial cells and Professor of Medicine and its relationship to therapeutic re- transgenic mice. These studies have that I received as a GI Ferdinand G. Weisbrod Chair in sponses associated with the treatment taught me the cognitive and unraveled novel and important mech- fellow, I could never been Gastroenterology of patients with Crohn’s disease using technical skills that were anisms that appear to play a significant able to pursue my academic Co-Director PennCHOP Microbiome an elemental diet. essential to becoming an role in the pathophysiology of gastric Program Finally, Dr. Wu is leading a multidis- dysplasia and neoplasia. and investigative goals ”. University of Pennsylvania independent investigator ”. ciplinary group of investigators using “My fellowship at the Current research programs in the Wu phosphorescence nanoprobe technol- ogy to examine the dynamic oxygen 115 University of Michigan laboratory focus on the mutualistic interactions between gut microbiota interaction between the host and has been instrumental to and the host with a particular focus on the gut microbiota at the intestinal the establishment of my metabolism. Current areas of inves- mucosal interface. academic career. I had the tigation include the effect of diet on the composition of the gut microbiota “The training I received as fortune to work with an and its subsequence effect on host a GI research fellow at the exceptional mentor and metabolism related to nitrogen bal- University of Michigan not with outstanding colleagues ance as well as its impact on metabolic only introduced me to the in an intellectually pathways in the intestinal epithelium, principally fatty acid oxidation. tremendous professional
Andrea Todisco, MD Gary D . Wu, MD Understanding the biology of colon repair and its relationship to outcome to focus on projects that Understanding the enteric nervous nervous system. By understanding the cancer and survival for these patients. led to my development in system in health and disease interaction of gut microbiota and the JOHN CARETHERS, MD SHANTHI SRINIVASAN, MD enteric nervous system, Dr. Srinivasan writing papers and grants, (Fellowship 1995) “The Physician Scientist (Fellowship 1999) and her laboratory hope to develop John G. Searle Professor and Chair, track during my GI something I had to learn Professor of Medicine, Emory new strategies to treat gastrointestinal Department of Internal Medicine fellowship at Michigan how to do . Without this University motility disorders. University of Michigan Chief of Gastroenterology, Atlanta enabled me to pursue track, I would not be where I Dr. Srinivasan is also investigating the VAMC Dr. Carethers’ current research direction research with a fantastic am today ”. role of neurotrophic factor GDNF and is focused on colorectal cancer—in Current research programs in the how it regulates obesity and hepatic mentor, Rick Boland, particular, defective DNA mismatch Srinivasan laboratory focus on the steatosis. Recent studies have demon- 116 repair, which drives the most common who happened to make mechanisms of altered gastrointes- strated that GDNF can improve fatty type of hereditary colorectal cancer, a transformative change tinal motility by understanding the acid oxidation in the hepatocyte and Lynch syndrome, as well as more than in his research from development and pathophysiology of lead to a reduction in hepatic steatosis. 15 percent of sporadic, non-familial col- the enteric nervous system. Current biochemistry to genetics orectal cancer. His current NIH-funded areas of investigation include the effect “My interactions with the projects address the function of one of at the time I joined his of a high fat diet on gut microbiota and GI faculty at the University the DNA mismatch repair proteins, the lab . The track provided its subsequent effect on altered gastro- of Michigan during my role of inflammation and regulation of intestinal motility. Her laboratory has some protected research fellowship sparked my the DNA mismatch repair system, and demonstrated the role of the pathogen some racial/ethnic differences in the time after my clinical GI recognition receptor TLR4 in regulating interest in pursuing a occurrence of defective DNA mismatch training, plus it enabled me the development of the enteric career in gastrointestinal
John Carethers, MD BASIC, CLINICAL + TRANSLATIONAL RESEARCH
motility-related research . University of Texas Southwestern immune function in humans, particu- mentorship and sustained The outstanding faculty, Medical Center larly Mendelian disorders that involve institutional support I abnormal gut inflammation. nurturing environment and Dr. Burstein’s laboratory is focused on needed and that proved key opportunities helped me unraveling fundamental principles “Training at University to my career development. I behind pathologic inflammation and to achieve my aspiration to of Michigan was an can say unequivocally that I its role in human disease, particularly be a physician-scientist and in the GI tract. A significant effort is de- essential step in my career owe my academic career to develop my own scientific voted to investigation of transcriptional development. Many things the vision and support that I niche. I am grateful for the circuits that control the activation of had to come together received at U-M.” pro-inflammatory genes. This work has for me to be able to wonderful mentorship at led Dr. Burstein to discover the COMMD 117 the University of Michigan Shanthi Srinivasan, MD protein family, a group of intracellular successfully emerge from that enabled me to have a Unraveling the principles underlying factors that regulate pro-inflammatory training with the prospect of signals as well as other processes, most successful academic career . pathologic gut inflammation developing an independent EZRA BURSTEIN, MD importantly, the sorting and proper research program. After (Fellowship 2001) recycling of cell receptors that traverse interviewing in leading Associate Professor through the endosomal compartment. Chief, Division of Gastroenterology In parallel to these molecular and cellu- programs around the lar studies, Dr. Burstein’s laboratory also Department of Internal Medicine, country, I found that only investigates the genetic and molecular Division of Digestive & Liver Diseases Michigan could offer the Department of Molecular Biology pathogenesis of disorders of altered
Ezra Burstein, MD Probing the mechanisms of immune development and inflammasome academic medicine . Having move seldom pursued by homeostasis regulating the gut micro- regulation of CD8+ T cells) of H. pylori- no formal basic research a Californian . Coming to biota-host interaction associated intestinal metaplasia. training, I pursued the basic Michigan was the single most JOHN Y. KAO, MD (Fellowship 2002) Additional research efforts aim to Associate Professor of Medicine science research fellowship important career decision understand the role of environmental Associate Director, GI Fellowship track supported by the GI my wife and I made 17 years (e.g., stress and diet) and host factors Training Program (e.g., Duox2 and racial differences) division’s T32 training grant ago . That is the Michigan Dr. Kao’s research focuses on under- that contribute to altered gut micro- and became proficient in Difference ”. standing how gut microbes peacefully biota with disease-causing potentials. immunological methods coexist in the GI tract with their human He has translated this knowledge into 118 host and identifying factors that clinical practice by helping to start under the mentorship contribute to an altered symbiotic the Fecal Microbiota Transplantation of Juanita Merchant and relationship leading to dysbiosis. His Program at University of Michigan. transitioned successfully to earlier NIH-funded work discovered the independence as a tenured beneficial role of H. pylori colonization “I quickly realized after in lowering the risk of IBD and contrib- starting my GI fellowship that faculty. I would have never uted to the current practice guideline to the Michigan Difference was realized my passion for eradicate H. pylori only in symptomatic the unparalleled expertise scientific discovery and or at-risk patients. His lab continues to academic medicine if I investigate novel immune pathways and mentorship that await (e.g., tryptophan metabolism in B cell those who seek a career in hadn’t come to Michigan, a
John Y . Kao, MD At the forefront of molecular imaging, the Division of Gastroenterology at the University of Michigan pioneered the use of fluorescent-labeled peptides for the early detection of cancer in patients with Barrett’s Esophagus . This novel methodology uses endoscopy to target disease in the premalignant stage to reduce the incidence, morbidity and mortality of esophageal cancer .
THOMAS D. WANG, MD, PhD CONFOCAL + MULTIPHOTON ENDOMICROSCOPY 119
Illustration: Bill Burgard Peptide Probes and Novel Imaging Platforms to Detect Early GI Cancers
With a combination of innovations, THOMAS WANG, MD, PHD, the H . Marvin Pollard Collegiate is being developed to perform real- Professor of Endoscopy Research, is leading a critical charge: to remove uncertainty from the time “optical biopsies” for point-of- diagnosis of cancer in its earliest and most treatable stages . care diagnosis. Using peptides as a novel probe capture flat lesions or lesions that may The approach has been developed platform, Dr. Wang has developed be patchy in distribution. for clinical use in part through the imaging agents with high University of Michigan Medical By contrast, Dr. Wang’s dual-axis specificity and binding affinity to Procedures Unit, which is supporting confocal microendoscopy platform overexpressed or gene-amplified early-stage clinical studies in patients can provide clear images of tissue targets on the surfaces of cancer to demonstrate safety and early in the vertical plane and detect and precancerous cell types. During evidence of efficacy. numerous targets simultaneously. It 120 endoscopy, specific peptide probes can be fluorescently labeled and applied in high concentration to the mucosa. The probes bind quickly, This goal underlies Dr. Wang’s work and can be imaged with a novel developing new peptide imaging microendoscope, which Dr. Wang agents and advanced optical imaging also developed.
T methods in order to investigate the h Conventional methods for in vivo om molecular properties of the mucosa in a imaging, including ultrasound, s W the digestive tract. an CT, MRI and PET, lack the spatial g, M D, PhD resolution and temporal speed to BASIC, CLINICAL + TRANSLATIONAL RESEARCH
As a result of his work, Dr. Wang is creative, multidisciplinary approach,” widely credited with accelerating said Dr. Wang. the convergence of fluorescence “Understanding the many molecular spectroscopy with endoscopy, and his pathways involved in cancer cell pro- innovations are changing existing liferation coupled with peptide probes diagnostic paradigms. and new optical imaging approaches Diagnosis and staging of cancer will help us improve the speed and now can be made by detecting the accuracy of diagnosis,” he added, “and expression of a variety of cancer- if taken to the next level, will one day specific molecular targets rather potentially help create a personalized than on the gross visibility of lesion approach to treatment with targeted 121 masses, which often aren’t apparent cancer therapies as well.” until later stages of disease. “The accurate diagnosis of cancer— reducing false positives and false negatives and discerning which precancerous lesions will progress in individual patients—has been a longstanding problem and requires a Hedgehog Signaling from Chronic Inflammation to Gastric Cancer
JUANITA L. MERCHANT, MD, PhD, is a molecular gastroenterologist who uses a combination of molecular tools and mouse models to dissect how chronic inflammation in the luminal GI tract Hh Signaling + Helicobacter Synergize alters the epithelium resulting in gastric or colon cancer . to Recruit MDSCs to the Stomach normal gastric physiology and during a collection of specimens from their 13- gastric preneoplasia. Her studies year gastric cancer followup study. Their Helicobacter DAMPs IFNa have demonstrated that the parietal collaborative results showed that hu- Plasma cells, and therefore acid secretion, man Schlafens increase in the immune Shh require sonic Hedgehog signaling. cells of patients with intestinal metapla- More recently, she has found that sia who later progress to gastric cancer myeloid-derived suppressor cells (MD- and suggest that Schlafens might serve 122 SCs) require Hedgehog signaling to as a biomarker to help clinicians decide create a permissive environment that who requires more frequent screening + + + supports the development of gastric for gastric cancer (Fig. 2). Indeed, add- Slfn4 Slfn4 Slfn4 MDSCs metaplasia (Fig. 1). ing immunohistochemical detection to Metaplasia the pathologic diagnosis of intestinal Dr. Merchant’s work has identified a Juanita L . Merchant, MD, PhD metaplasia shifted the area under the class of molecules called Schlafens that curve (AUC). She and David Ding, MD, closely correlate with the emergence of One of the major areas to which are currently working with UCLA CURE intestinal metaplasia in mouse models Fig. 1 Schlafen+ MDSCs recruited to the infected stomach acquire Dr. Merchant has made significant Digestive Diseases Research Center and human subjects. She tested this functions that affect change in the gastric microenvironment . scientific contributions involves to identify serologic biomarkers that hypothesis with a group in Spain using DAMPs = Damage-activated molecular patterns; Shh = Sonic the role of Hedgehog signaling in correlate with intestinal metaplasia. Hedgehog . See Ding L et al J Clin. Invest, 2016. BASIC, CLINICAL + TRANSLATIONAL RESEARCH
Program Project on Cellular Decisions Slfn5 Expression Decreased in the GI Tract (P01 DK062041). in Soria Cancer Samples The P01 focuses on the interplay between developmental signaling pathways, e.g., Hedgehog signaling, and environmental cues that direct cell specification, homeostasis and metaplasia, a pre-neoplastic change. In the current funding cycle, the focus was extended to include Notch and Wnt signaling. Chronic inflammation 123 Dr . Deborah Gumucio Dr . Linda Samuelson and specifically proinflammatory cyto- Serologic biomarkers would provide an for Gastrointestinal Research (UMCGR) kines play a central role in triggering inexpensive and easy way for clinicians and serves as the co-director of the patterns of cell specification during to identify a subset of patients who Center’s Molecular Biology Core. In glandular transformation from a ho- are at high risk for gastric cancer, and collaboration with DR. DEBORAH meostatic to metaplastic state. Signals the biomarkers might also serve as GUMUCIO (Department of Cell and regulating the gastric stem cell were a natural extension of Dr. Merchant’s Fig. 2 Schlafen 5 Correlates with Intestinal Metaplasia (IM), a therapeutic targets. Developmental Biology) and DR. seminal work in the intestine and have pre-neoplastic lesion that appears in the stomach after chronic LINDA SAMUELSON (Department of Dr. Merchant is an associate director been extremely important in bringing inflammation. The appearance of SLFN5 with IM correlates with a high Molecular and integrative Physiology), of the University of Michigan Center together several UMCGR members. likelihood of gastric cancer. Dr. Merchant successfully initiated a From Diagnosis to Cure: VIRAL HEPATITIS RESEARCH ALONG THE SPECTRUM
“Cure.” It’s a word patients long to hear, but when it comes to viral hepatitis, it has not been types as well as among patients with said often enough . DR. ANNA SUK-FONG LOK, the Alice Lohrman Andrews Research Professor in advanced liver disease and those Hepatology, is helping to change that . who have failed prior treatment. Dr. Lok, who on January 1, 2017, will leading an NIH-funded consortium therapy, ribavirin and interferon (New But the breakthrough can only become president of the American comprising 21 adult and seven pediat- England Journal of Medicine, 2012; benefit patients if treatment is Association for the Study of Liver Dis- ric liver centers in the United States 366:216-224). initiated early; therefore, improved eases (AASLD), joined the U-M faculty in and Canada, the Hepatitis B Research screening is critical. Dr. Lok recently “It was a small, proof-of-concept 1995. Over more than two decades, she Network, since 2008. She co-authored conducted a pilot study using U-M study,” said Dr. Lok, “but showing that has led research efforts to advance the four editions of the frequently cited Health System electronic medical what all our patients had been hoping world’s understanding of viral hepatitis, AASLD Practice Guidelines on Hepatitis records system to identify patients for (a cure without having to take 124 driven by a goal to reduce patient B, which serve as a reference for physi- born between 1945 and 1965—a injections for a year that make them suffering and one day, she hopes, have cians worldwide. generation with a much higher sick) can happen was astounding. An treatments at the ready to eradicate the prevalence of infection—who have not In a landmark study of hepatitis editorial accompanying that article viruses entirely. yet been screened. The system alerts C, published in 2012, Dr. Lok and was aptly titled ‘A Watershed Moment patients’ primary care physicians and Dr. Lok’s research has focused on the colleagues showed it was possible to in the Treatment of Hepatitis C.’” links to an order set and educational natural history of hepatitis B and C, achieve a sustained virologic response Dr. Lok now is investigating different materials. The pilot improved screen- the role of hepatitis B virus genotypes in patients infected with genotype 1 combinations of DAAs that might fur- ing rates sevenfold and has been and variants in patient outcomes and of the virus using a combination of ther shorten treatment and improve rolled out to primary care providers the evaluation of new treatments for all-oral, direct-acting antiviral agents cure rates for additional virus geno- throughout the UMHS system. both hepatitis B and C. She has been (DAAs), rather than the standard
Typical hepatitis C with dense lymphocytic inflammation BASIC, CLINICAL + TRANSLATIONAL RESEARCH
Continuing along the spectrum, Dr. to use advanced statistical methods to Lok developed a noninvasive way to develop dynamic predictive models. In stage liver damage that results from addition to baseline data, the models hepatitis C infection. This alternative incorporate longitudinal patient infor- to liver biopsy assesses fibrosis mation. Risk calculations adjust as the and cirrhosis using two measures individual’s course of disease changes. obtained from a simple blood test: “My patients continue to guide me to- platelet count and aspartate amino- ward the research questions we need to transferase (AST) (Hepatology, 2003; be asking and to persevere when we hit 38(2):518-26). The AST-to-platelet roadblocks,” said Dr. Lok. “Seeing my ratio index (APRI), has been adopted own patients and knowing patients all 125 by the U.S. Centers for Disease Con- over the world get better as a result of trol and Prevention and the World the knowledge we’ve gained from our Health Organization as a simple and work is the biggest reward a researcher accurate method to assess stage of can ever ask for.” liver damage, not only for those with hepatitis C but also for individuals with hepatitis B. To assess the likelihood of progression to advanced liver disease in patients, Dr. Lok also partnered with colleagues
Recovering from hepatitis C treatment: returning to normal liver histology Promising Targets for New IBS Treatments: GUT DYSBIOSIS AND MUCOSA PERMEABILITY IMPAIRMENT
Irritable bowel syndrome (IBS) is one of the most common GI disorders we encounter in our interest in elucidating mechanisms Gut dysbiosis in IBS practice . Worldwide, approximately 10 to 20 percent of adults have symptoms consistent guiding neutrophil trafficking across In recent years it has become apparent with IBS. Advances in basic, mechanistic and clinical investigations have improved our the intestinal epithelium. that gut dysbiosis is common amongst understanding of this disorder and its physiological and psychosocial determinants. Altered DR. GABRIEL NUNEZ GI motility, visceral hyperalgesia, disturbance of brain-gut interaction, abnormal central , also from the IBS patients. It is conceivable that processing, autonomic and hormonal events, genetic and environmental factors and Department of Pathology, examines abnormalities in gut microbiota act in psychosocial disturbances are veritably involved, depending on the individual . This progress the role of gut microbiota in the concert with environmental factors to may result in improved methods of treatment . regulation of the gut immune system alter epithelial permeability allowing which is abnormal in IBS patients. access of luminal toxins into the At the University of Michigan, CHUNG proteomic and system biology to therapeutic targets for intervention. The group also includes DR. JOHN mucosa, which may in turn cause OWYANG, MD has assembled a group promote translational research. DR. ASMA NUSRAT from the De- WILEY, a neurogastroenterologist, degranulation of mast cells. The release 126 of basic and clinical investigators with partment of Pathology, a key member Mucosal Biology Research who is interested in investigating the of histamine, proteases and prostaglan- diverse expertise to unravel the puzzle of U-M’s Center for Gastrointestinal role of epigenetic pathways in stress- dins may act on enteric neurons and of IBS, including neurogastroenterolo- Recent clinical studies indicate Research (UMCGR), has a longstand- induced visceral hyperalgesia. “We gut muscles to produce symptoms of gists, mucosa biologists, microbiome that most IBS patients have clinical ing research interest directed at believe epigenetic targets may play IBS. Hence, normalizing microbiota in investigators and genomic scientists; mucosal inflammation with activated understanding basic mechanisms for a significant role in how IBS patients the gut may be an attractive therapeutic the program has an annual research mast cells, lymphocytes and enhanced intestinal epithelial barrier regulation perceive pain,” said Dr. Wiley, who target to treat IBS. This can be achieved base of $1.8 million in National Insti- expression of pro-inflammatory and repair during inflammatory states is looking at the histome-regulated through diet or by the use of probiotics tutes of Health funding. At U-M, an IBS cytokines. These abnormalities may in the gut. She collaborates closely pain pathways that carry signals from or antibiotics. registry and biosamples repositories for compromise epithelial integrity and with her colleague, DR. CHUCK the viscera, through the spinal cord, Currently the cause of gut dysbiosis blood, fecal samples and colonic tissues lead to visceral hypersensitivity. This PARKOS, Chair of the Department of to the brain. in IBS is unknown. Dr. Owyang will capitalize on advances in genomic, series of events provides potential Pathology, who has had a career-long BASIC, CLINICAL + TRANSLATIONAL RESEARCH
Solving the Puzzle of IBS
John Wiley has assembled a premier group Biomarkers and targeted PhD, a molecular biologist, recently Vince Young Juanita Merchant Chung Owyang of microbial investigators such as treatments identified a functional tryptophan Chuck Burant DRS. VINCENT YOUNG, NOBU hydroxylase 1 (TPH-1) polymorphism Nobu Kamada Dr. Kao and his laboratory have a KAMADA, JOHN KAO and MERRITT associated with IBS-diarrhea predom- Chung Owyang long-established interest in looking for GILLILLAND to investigate whether inant. This may help to predict IBS biomarkers for gut dysbiosis. Clinically, dysbiosis may be related to stress patients’ response to medications tar- this is important for identifying subsets and/or diet. It is also unclear if geting the serotonin signaling system of IBS patients who may be more further microbial changes are causal, including the recently developed TPH-1 responsive to modulation of gut consequential or merely the result of antagonist. dysbiosis. In a recent study, Dr. Kao and change in bowel habit. Furthermore, researchers in his lab found that the Using a multidisciplinary approach, Clinical Phenotyping these investigators, in collaboration majority of post-infectious IBS patients Dr. Owyang and his colleagues are 127 with Drs. Owyang and Wiley, examine Biobanking with gut dysbiosis have elevated making great strides to understand how gut microbiota modulate gut-brain mucosal Duox2 levels. Ongoing work the complexity of IBS and identify interaction. In collaboration with DR. IBS will further validate the usefulness specific causes that may result in CHUCK BURANT, these investigators John Kao of measuring colonic mucosa Duox2 improved methods of treatment. also examine the role of bacterial Gabriel Nunez levels to identify antibiotic-responsive “The discovery that gut dysbiosis metabolites and signaling molecules in Nobu Kamada IBS patients. and impaired permeability occur communicating with the host systems, Asma Nusrat in IBS offers new promising targets such as the enteric nervous system and In a subset of IBS patients, there may Chuck Parkos for treatment,” he said. This may the brain. be genetic abnormalities affecting John Wiley pave the way to practice precision the serotonin synthetic and transport Chung Owyang medicine in treating IBS, a program pathways. JUANITA MERCHANT, MD, directed by DR. LIZ SPELIOTES. John Kao Liz Speliotes
NIH FUNDING = $1,844,565/YR Inflammatory Bowel Disease Research at the Forefront
The University of Michigan Inflammatory Bowel Disease program is a research leader in this rapidly changing field. The program has strong research funding coming from a variety of sources, including the National Institutes of Health, Department of Defense, U.S. Department of Veterans Affairs and Crohn’s and Colitis Foundation (CCFA). Basic Science Research in IBD pathways in the inflammation of IBD. R01 award. Dr. Stidham, in collabora- JOHN KAO, MD, focuses on the role tion with radiologists and computer RYAN STIDHAM, MD, MSc is leading of dendritic cells in sampling the gut scientists, is developing algorithms to proteomic studies in patients with microbiome, and T regulatory cells in rapidly analyze CT scans in IBD patients Crohn’s disease to identify novel damping the inflammatory response. to identify abscesses, reproducibly biomarkers that can detect and monitor NOBU KAMADA, PhD, studies the measure inflammation and detect stric- progression of intestinal strictures. The 128 interaction between the gut microbiota tures with the support of a Department laboratory of PETER HIGGINS, MD, and the human gut immune system. of Defense grant. PhD, MSc, works on the mechanisms of intestinal fibrosis to identify targets Translational Research in IBD Dr. Higgins’ lab, with the support of for anti-fibrotic drug development. the Michigan Center for Therapeutic Dr. Higgins and AKBAR WALJEE, MD, Dr. Higgins uses human intestinal Innovation, has identified candidate MSc, in collaboration with statistics organoids as a model for the intestinal antifibrotic medications and demon- faculty, are developing machine scarring in Crohn’s disease to test strated their effect on human intestinal learning algorithms to predict the promising therapies. SHRINIVAS cells and human organoids; they are response of IBD patients to thiopurines BISHU, MD studies the role of the now testing these new drugs in animal and biologic therapies with the support interleukin-17 and interleukin-23 models. Dr. Higgins is also collaborat- of a National Institutes of Health (NIH)
Morphomics: Objective Fat Assessment Predictive of Complications in IBD BASIC, CLINICAL + TRANSLATIONAL RESEARCH
ing with the U-M Microbiome Core to in patients over time to determine that predict which patients are at risk study the role of the microbiota in flares whether obstruction and surgery can be for Emergency Department visits, hos- of ulcerative colitis, and the importance predicted. pitalizations and high charges in the of reconstitution of the gut microbiota next year. Interventions are planned for Dr. Waljee has developed a machine after Clostridium difficile infection and these high-risk patients to prevent such learning algorithm to identify IBD antibiotic therapy, with the support events and provide high value care. patients at risk for flare in the next six of a CCFA grant. The Michigan IBD months based on data in the Veterans In addition, our IBD group has Biobank provides a platform for basic Administration electronic medical collaborated with Lycera, a local startup scientists to obtain biopsies, cells and record, to provide an opportunity for in- on U-M’s North Campus, which has serum from IBD patients to test new tervention. SHAIL GOVANI, MD, MSc, developed a new, gut-specific therapy hypotheses about the mechanisms of studies the importance of adherence for ulcerative colitis that has entered a 129 inflammatory bowel disease. to subcutaneous biologic therapies in phase 2 clinical trial. The University of Clinical Research in IBD IBD, and has found that missing only Michigan IBD clinical trials group has a few doses has a significant effect on five full-time study coordinators and Dr. Higgins, in collaboration with long-term outcomes. He is developing over 50 IRB-approved clinical studies. radiology faculty, has developed interventions to improve patient They have recently participated in the new methods of shear wave velocity adherence to subcutaneous biologic trials supporting the approval of Vedoli- ultrasound to measure the stiffness of therapy in IBD. zumab and Ustekinumab, and continue strictures in the intestine in Crohn’s dis- to offer many other new options to our ease. Their NIH R01-supported research Dr. Higgins’ group has identified five patients with IBD. will measure the stiffness of strictures factors in the electronic medical record
Shear Wave Velocity Imaging Epigenetic Pathways in Stress and Abdominal Pain
Chronic stress is associated with enhanced abdominal pain, particularly in patients with functional GI disorders such as irritable bowel syndrome (IBS). Recent evidence suggests that altered gene expression involving epigenetic regulatory pathways may play an important role in understanding why this may be . The research of JOHN W. WILEY, MD, “It may be a bold statement, but we explaining a large amount of variation focuses on pain pathways that inner- are in the midst of a renaissance in in heritable traits and disease risks as vate the gut and how these pathways how we understand the ways in which well as therapeutic responses and the are altered in diabetes mellitus, in the gene transcription occurs,” said Dr. risk of side effects. aging process and under conditions Wiley. “Since the Human Genome Epigenetic changes occur primar- of chronic stress. His laboratory has Project, we as a scientific community ily through several mechanisms, 130 identified specific changes in the have been realizing that we didn’t including DNA methylation by DNA regulation of ion channels located know as much as we thought we did methyltransferases (DNMTs), which on the sensory nerves that transmit about how individuals differ from one tends to inhibit gene transcription, pain signals from the colon in diabetic another.” and DNA demethylation, which typi- rodent models, in aged animals and Enter the field of epigenetics: the vari- cally inhibit gene transcription. DMNTs in models of chronic stress. His recent ety of heritable, potentially reversible are a popular target in cancer research. research is investigating the role of processes that regulate gene activity epigenetic regulatory pathways in In addition, non-coding microRNAs and expression, independent of actual chronic stress-associated enhanced also tend to inhibit gene expression. J changes in DNA sequence. An under- oh abdominal pain. MicroRNAs in particular represent n W standing of epigenetics is critical to . Wi ley, MD potential new disease biomarkers and BASIC, CLINICAL + TRANSLATIONAL RESEARCH
therapeutic targets. Histone modifica- pathways that carry signals from the Epigenetic regulation of chronic stress-induced visceral tions represent yet another mecha- viscera, through the spinal cord to hyperalgesia (HONG ET AL. GASTRO., 2015) nism, and these usually promote gene the brain. Subsets of neurons in the transcription. When DNA is tightly spinal ganglia carry only pain signals, CHRONIC PSYCHOLOGICAL STRESS wound around histones, genes are and his lab is investigating whether not accessible to be transcribed. When histone-regulated pathways are differ- HPA axis certain molecules attach to the histone entially expressed in those nerves. Corticosterone ( ) tails, however, they open up and DNA In work published in Gastroenterology can be transcribed. in 2015 (Jan;148(1):148-157.e7), Clinically, patients with IBS experience Dr. Wiley and collaborators measured Transcription Factors - GR: MR both abdominal pain and a change in pain activation and used molecu- 131 bowel habits. Dr. Wiley’s laboratory is lar probes to look more closely at Feedback control investigating how pain transmission epigenetic pathways involved in the occurs and the role of epigenetic enhanced perception of pain. Targets DNMTs ( DNMT1 ) HATs ( p300 ) pathways in modifying the genes that included a common target in pain regulate pain. research, transient receptor potential vanilloid type 1 (TRPV1), and the DNA methylation Histone acetylation “We believe epigenetic targets may
endogenous cannabinoid receptor 1 play a large role in how IBS patients (CNR1) to better understand how it perceive pain,” said Dr. Wiley, who is interact might inhibit pain perception. CB1 ( ) TRPV1 ( ) Visceral Hyperalgesia looking at the histone-regulated pain Epigenetic Mechanisms The research found that mice The work is leading to additional subjected to stress showed features areas of inquiry, including the role similar to those in human IBS and that of epigenetic pathways involved in the anti-pain pathway was inhibited modulating intestinal barrier function in our model through methylation, along the paracellular route. “We while the pain activation pathway in know these targets are altered in can- the model was turned on through a cer, but we know very little about how process of histone acetylation. “In a epigenetic pathways may modify the very important pathway modulating expression of these and other types pain, you have both systems—well of junctions in the non-malignant 132 studied—involved in the net outcome milieu,” said Dr. Wiley. of pain perception,” he said. With his interest in stress, Dr. Wiley The research also found that looked at its targets, including gluco- expression of these pathways was corticoid receptors, which act as a ma- region-specific along the spinal cord, jor transcription factor in the body. His limited to the centric pathways going team compared the expression of the out to the viscera. Expression of these glucocorticoid receptors in the colon pathways was not present in, for and jejunum and found it was orders example, the sciatic nerve distribution of magnitude higher in the colon. down the leg. BASIC, CLINICAL + TRANSLATIONAL RESEARCH
“Ultimately stress is mediated through intron regions to interact with promoter these receptors, which might explain regions and modify gene expression.” why we see such region-specific Combine such high resolution technol- differences in the model and indeed, ogy with bioinformatics and “the story we believe, in humans,” he said. about how epigenetics differentially Now Dr. Wiley is looking at the affects gene expression continues to expression of epigenetic regulatory unfold in some very intriguing ways,” pathways in colon crypts, and “seeing Dr. Wiley said. some very interesting differential expression of these DNMTs,” he said. “That’s prompting us to take the story 133 from dorsal root ganglion neurons to the intestinal tract.” The story is an evolving one, and Dr. Wiley is furthering the work using su- per-high-resolution microscopy, which provides resolution down to about 20 nanometers. “We can actually see DNA forming loops using this technology,” he said, “and it’s these loops that allow Precision Medicine: UNRAVELING THE CAUSES OF OBESITY AND LIVER DISEASE THROUGH GENOMIC RESEARCH
More than one-third of the U .S . population and over one billion individuals worldwide suffer environmental factors. To better from obesity . Some go on to develop related metabolic diseases, such as diabetes, heart understand our susceptibility to these disease or nonalcoholic fatty liver disease (NAFLD). NAFLD develops when fat is deposited diseases she carried out the largest in the liver, and it is projected to be the most common liver disease globally by 2020. NAFLD genome-wide association studies for can progress to nonalcoholic steatohepatitis and cirrhosis and has also been associated with obesity and NAFLD. development of other metabolic complications such as cardiovascular disease . In a paper published in Nature in But not all people who are obese Bioinformatics. “Given the epidemic Dr. Speliotes, who received the 2015 (Feb 12; 518 (7538):197-206), develop complications from obesity, proportions of obesity and NAFLD, University of Michigan 2016 Dean’s Speliotes and colleagues reported and those who do don’t develop the these are some of the biggest unmet Award for Basic Science Research, their identification of 98 genomic same complications. Similarly, not all medical needs of our time. Better works to untangle the genetic and loci for body mass index (BMI), a 134 individuals who deposit fat in their defining the causes of these diseases environmental influences that measure of obesity that influences its liver will go on to develop advanced will allow us to develop precision care predispose individuals to obesity and development, in more than 340,000 liver disease or related metabolic for these patients—getting the right NAFLD. Her goal is to translate the individuals. Many of the genes complications. treatment to the right patient at the findings into improved diagnosis, implicated in obesity are expressed right time—to actually cure what ails management and treatment of these in the nervous system, which was not “Our understanding of the etiology them,” she said. “If we understand the conditions. expected for a metabolic disease. of these diseases is very poor, and biology of the disease, we can define thus few effective treatments exist,” Gaining new biological insights an individual’s risk of developing Indeed some of the most enriched said ELIZABETH SPELIOTES, MD, regions include genes that play it, and we can develop tailored and Both obesity and NAFLD are complex PhD, MPH, associate professor in the roles in learning, memory, smell and effective therapeutic approaches with genetic traits, meaning they result departments of Internal Medicine emotion in addition to genes that, as fewer side effects.” from a combination of genetic and and Computational Medicine and BASIC, CLINICAL + TRANSLATIONAL RESEARCH
expected, affect feeding and satiety, genes involved in glucose and lipid the individual variants are not that recommendations. Indeed, since most energy expenditure and insulin metabolism as being causal to this predictive, the cumulative effects of people that have NAFLD do not know biology. disease. the variants are medically significant. they have it, and since this disease Individuals carrying the most BMI- was not even defined as a disease “Based on the fact that we are able to “There’s been a longstanding debate in increasing variants (top 5 percent) until about 10 years ago, “genetic map these genetic signals to the brain hepatology about whether steatosis is are on average 9 to 11 kilograms profiling may give clinicians a rapid suggests a biological cause to obesity benign. The genetics are telling us that heavier than those carrying the least way to identify patients at high risk of as opposed to pure willpower as the lipid metabolism is causally related to (bottom 5 percent). Gaining or losing developing NAFLD,” said Dr. Speliotes. cause, as some have suggested,” Dr. NASH and fibrosis, so so-called benign 9 to 11 kg can lead to development or Speliotes said. “And since most of disease in the liver may not be so Defining subtypes of disease amelioration of diabetes, for example, these genes were completely novel, benign after all. The days of waiting to in a single individual. For both obesity and NAFLD, Speliotes the findings suggest that we have see if fat in the liver will develop into 135 and colleagues have found that much to learn from further study cirrhosis before we treat it may soon be The odds ratios of the NAFLD- some of the variants that predispose about our susceptibility.” over,” Dr. Speliotes said. associated variants per allele for to these conditions increase risk of predisposing to advanced liver Dr. Speliotes and colleagues also Clinical prediction related metabolic disease or advanced disease, such as NASH/fibrosis H carried out similar analysis for NAFLD, liver disease as expected epidemi- P were higher than in the BMI work, M The variants that affect BMI , identifying five variants associated ologically. This begins to define the D individually have small effects, with however -- between 1.37 and 3.26 h P with NAFLD that explain between common genetic susceptibility to , the largest at obesity-associated per allele. Such an increased risk is D 17 and 20 percent of trait herita- developing these diseases. , M (FTO) gene conferring an increased medically significant for individuals es bility (PLoS Genetics, 2011; 7(3): ot odds ratio of developing obesity of who carry them and may soon Interestingly however, the investigators eli e1001324). These variants implicate . Sp th K 1.25. While odds ratios suggested merit individualized treatment have also identified the variants that Elizabe predispose to obesity or NAFLD that suggested how we can correct the medicine combination and minimize protect from development of related defects seen by altering their function,” side effects.” metabolic diseases, such as diabetes she said. Dr. Speliotes and colleagues have or cardiovascular disease. These can Further, the findings indicate that when further identified environmental and provide insights into how to dissociate most genes are severely perturbed they biological factors that interact with these conditions and thus even treat will disrupt multiple traits, suggesting these genetic changes to exacerbate metabolic disease in obese individuals. that medications that target these development of disease. Certainly, These genetic variants are also now genes will have side effects. those at high genetic risk of developing helping them to define subtypes of NAFLD who carry particular genetic NAFLD that may help to explain why “Nature has weakly changed the variants can be counseled as to what to only some develop related metabolic function of these genes to allow 136 avoid to prevent development of the diseases while others do not. for human variation to occur while disease. Defining tailored treatments for minimizing the detrimental side disease effects of drastic changes to gene In these ways, Dr. Speliotes is helping function. This suggests that if we can to define the underlying etiologies Dr. Speliotes’ work is identifying use medicines to weakly increase or of these heterogeneous diseases specific gene targets for therapeutic decrease the effects of identified genes and use them to better define intervention and suggesting new to converge on affecting the desired disease subtypes and match them to approaches to treatment. “The genes trait like fatty liver but not converge on new therapies, so that we can have implicated from these studies not their effects on unrelated biologies, we more effective treatments for these only define subtypes of disease but can increase the on target effects of that conditions in the future. BASIC, CLINICAL + TRANSLATIONAL RESEARCH
137 Collaboration: JOINT APPOINTMENTS
Collaboration with Basic Science Identification and Folding Core. He Samuelson’s research focuses on Notch Departments is also co-principal investigator in pathway regulation of epithelial cell One of the consummate the GI Division’s NIH T32 Basic and homeostasis through modulation of strengths of our GI Division Translational Sciences Training Grant. gastrointestinal stem cell function. Dr. is its cross-disciplinary As Editor and Chief of Gastroenterology Samuelson has a joint appointment in approach to research, (2011 to 2016), Dr. Omary interacted the Division of Gastroenterology and exemplified by the many closely with many GI faculty members Hepatology. In 2002, she collaborated joint faculty appointments who served on the editorial board. with Drs. Merchant and Gumucio within other basic science to initiate a program project (P01 LINDA SAMUELSON, PhD, is the departments. Among these DK062041) to investigate the interplay John A. Williams Collegiate Professor we have seven faculty from between developmental signaling of Gastrointestinal Physiology and the Department of Molecular pathways and environmental cues. Professor in the Department of 138 and Integrative Physiology epithelia, understanding the molecular Dr. Samuelson is a key member of the molecular mechanisms of obesity, Molecular & Integrative Physiology. Dr. (MIP) who also hold pathogenesis and significance of Michigan Center for Gastrointestinal diabetes and nonalcoholic fatty appointments in the Division the hepatocyte inclusion bodies and Research (UMCGR), serving as liver disease (NAFLD). Dr. Rui has a of Gastroenterology and defining potential therapeutic targets co-director of the Molecular Biology joint appointment in the Division of Hepatology . for acute and chronic hepatitis. Since Core. She also co-directs the PhD pre- Gastroenterology and Hepatology joining the University of Michigan in and works closely with Dr. Owyang BISHR OMARY MD, PhD doctorate mentoring of the Division’s , is Professor 2008 Dr. Omary has worked closely to investigate the hypothalamic and Chair of the Department of T32 grant in Basic and Translational with the Division to enhance its Research Training. neurocircuits in the regulation of Molecular & Integrative Physiology research and education missions, energy metabolism. Dr. Rui is a and the H. Marvin Pollard Professor of and serves as an Associate Director of LIANGYOU RUI, PhD, is a professor key investigator of the UMCGR Gastroenterology. His research focuses the U-M Center for Gastrointestinal in the Department of Molecular investigating neurobiology in appetite on investigating the cytoskeletal Research (UMCGR) and co-director & Integrative Physiology. Dr. Rui control, metabolism and pain. intermediate filament proteins that are of the Center’s Protein Localization, investigates the physiological and specifically expressed in digestive-type BASIC, CLINICAL + TRANSLATIONAL RESEARCH
Protein Localization, Identification and by which oxygen sensing transcription Molecular & Integrative Physiology and Folding Core, where he currently serves factors regulate gastrointestinal holds a joint appointment as Professor as Core Associate Director. His expertise homeostasis, inflammation and cancer. in the Department of Internal Medicine, in cell biology, calcium imaging studies Dr. Shah has been a key investigator Division of Gastroenterology and and pancreatic physiology serve as an of the UMCGR and is an emerging Hepatology. In addition to overseeing important resource to Center members mucosal biology research leader. Over a robust research program aimed at who are conducting research using the years, he has collaborated with understanding molecular pathways these technologies. several GI Division faculty members in pancreatic adenocarcinoma and such as Dr. John Kao and Dr. Juanita pancreatitis, Dr. Crawford serves as YATRIK SHAH, PhD, is an associate Merchant on pathways related to Director of the Pancreas Research professor in the Department of mucosa inflammation. Program in the Departments of Molecular & Integrative Physiology. The Medicine and Molecular & Integrative JOHN WILLIAMS, MD, PhD is major goal of his research program is to HOWARD CRAWFORD, PhD, is of Molecular and Integrative Physiology Physiology, and as Director of the 139 determine the molecular mechanisms a professor in the Department of with a joint appointment in the Division the Horace W. Davenport Collegiate Genetically Engineered Mouse Models of Gastroenterology and Hepatology. His Professor of Physiology and Professor of the Pancreatic Cancer Core in the lab studies the biochemical pathways in the Department of Molecular & Translational Oncology Program and metabolic requirements that Integrative Physiology. Research in Dr. and the Cancer Center. Dr. Crawford enable tumor survival and growth and Williams’ laboratory focuses on the collaborates frequently with many how this information can be used to regulation of pancreatic function by investigators of the UMCGR, including design targeted therapies. Dr. Lyssiotis hormones and neurotransmitters. Dr. Andy Rhim MD, Marina Pasca Di collaborates with many members of Williams has been a member of the Magliano PhD and Eric Fearon, MD, the UMCGR, including Andy Rhim MD, UMCGR since its inception and served PhD. as an associate director of the Center. Marina Pasca Di Magliano PhD, and He also directs the original morphology COSTAS LYSSIOTIS, PhD, is an Howard Crawford, PhD. core, which has now evolved to the assistant professor in the Department developmental signaling pathways GI tract. Together with Dr. Samuelson, and environmental cues that regulate she also directs the Molecular Biology epithelial homeostasis. Dr. Gumucio Core of the UMCGR. In addition, she also plays a critical role as part of serves as an associate director of the Center Mucosal Biology Group, the UMCGR. In 2008, Dr. Merchant collaborating with other investigators was inducted into the prestigious such as Jason Spence, PhD, and Andrea Institute of Medicine (now the National Todisco, MD. She mentors other faculty Academy of Medicine). members such as Michelle Muza- JOHN CARETHERS, MD, is the John Moons, MD, PhD. G. Searle Professor and Chair in the Joint Appointment of GI Faculty in Department of Internal Medicine DEBORAH GUMUCIO, PhD Basic Science Departments and Professor in the Department of 140 , is the and Director of the UMCGR, he Department of Internal Medicine, James Douglas Engel Collegiate works closely with many members with a joint appointment as Professor Human Genetics. Dr. Carethers is a key CHUNG OWYANG, MD, is the H. Professor in the Department of Cell of the Department of Molecular in the Department of Molecular and Marvin Pollard Professor of Internal and Developmental Biology. Current and Integrative Physiology (Drs. Integrative Physiology. Dr. Merchant’s Medicine and Chief of the Division research interests in Dr. Gumucio’s Omary, Williams, Samuelson, Rui) research focuses on the molecular of Gastroenterology and Hepatology. laboratory include investigating and Drs. Nunez and Nusrat from the mechanisms underlying normal and He holds a joint appointment as the role of the hedgehog pathway Department of Pathology. Together cancerous epithelial cell growth in the Professor of Molecular and Integrative in gut inflammation and in villus with Dr. Omary, they jointly direct luminal gastrointestinal tract. Over the Physiology. Dr. Owyang’s research formation. A longtime investigator at the Division’s T32 grant in basic and years, Dr. Merchant has worked closely interests focus on neurohormonal UMCGR, she collaborated with Drs. translational sciences. with her basic science department control of digestive functions including Merchant and Samuelson in 2003 colleagues such as Drs. Gumucio and pancreatic, endocrine and exocrine JUANITA MERCHANT, MD, PhD, to initiate a program project, P01 Samuelson to initiate a P01 program function, GI motility and pain behavior. is the H. Marvin Pollard Professor DK062041, to investigate the interplay project to study cellular decisions in the In his role as the Chief of the Division of Gastrointestinal Sciences in the BASIC, CLINICAL + TRANSLATIONAL RESEARCH
investigator at the Michigan Center so that they can develop better ways to on molecular imaging in the digestive for Gastrointestinal Research and prevent, diagnose and treat them. She tract and emphasizes the development collaborates closely with Eric Fearon, is a key investigator at the UMCGR and and validation of novel molecular MD, PhD, on the TGF beta signaling collaborates frequently with members imaging methods and systems for pathway; John Williams, MD, PhD and of other basic science departments early detection of disease. Dr. Wang’s others on the study of intracellular including Jiandie Lin, PhD and Charles collaborative group focuses on calcium stores and activation of PCK Burant, MD, PhD. cutting-edge translational research that alpha; and Linda Samuelson, PhD, connects U-M’s College of Engineering THOMAS WANG, MD, PhD, is the on the development of transgenic and Medical School. Dr. Wang has been Marvin A. Pollard Collegiate Professor mice to study a variety of genetic and a productive and active member of the of Endoscopy Research with a joint ap- epigenetic events that may result in UMCGR and a driving force in many of pointment as Professor of Biomedical the growth and progression of colon the Center’s translational and clinical and more recently his laboratory has ELIZABETH SPELIOTES, MD, PhD, and Mechanical Engineering. Research cancer. In 2012, Dr. Carethers was studies. For example, he designed an 141 begun working on the molecular MPH, is an associate professor in the in Dr. Wang’s Laboratory concentrates inducted into the National Academy of endoscopic laser confocal fluorescence virology of dengue virus, with a focus Department of Internal Medicine, Medicine. microscope, which provided real-time on identifying and characterizing Division of Gastroenterology and histology with a fluorescently labeled ANDREW TAI, MD, PhD, is an host-pathogen interactions. Dr. Tai Hepatology with a joint appointment as peptide during endoscopy. Images assistant professor in the Department has been a productive member of Associate Professor in the Department show differences between human of Internal Medicine, Division of the UMCGR since 2008 and actively of Computational Medicine and squamous, metaplasia and dysplasia Gastroenterology and Hepatology collaborates with other virology- Bioinformatics. Dr. Speliotes’ research mucosa. This first in-humans study with a joint appointment as Assistant focused investigators in the basic group utilizes human population based provides groundbreaking endoscopic Professor in the Department of science departments. and functional genetic studies to define research technologies showing that Microbiology and Immunology. Dr. and characterize causes of human confocal endomicroscopy can guide Tai’s research concentrates on the obesity, nonalcoholic liver disease tissue biopsy and early dysplasia molecular virology of hepatitis C virus, (NAFLD) and related metabolic diseases detection. 142 Global Reach: ENGAGING WITH THE WORLD 143 Global Impact: IMPROVING GI HEALTH, HEALTHCARE AND TRAINING WORLDWIDE
“Global initiatives are essential to our academic mission,” said JOSEPH KOLARS, MD (Fellowship in Shanghai and served on its Board of 1989), who holds the Josiah Macy, Jr ., Professor of Health Professions Education in the Division Trustees. He proposed joint research of Gastroenterology and Hepatology . “Global initiatives are crucial to enhancing opportunities collaborations on gastric cancer for education, research and innovation, and to improving health and reducing the burden of and inflammatory bowel disease disease worldwide ”. with Hong Kong University and the Chinese University of Hong Kong that The Division has been active across Dr. Yamada recruited Dr. Kolars to and Global Initiatives at the University continue today. borders for many years, dating back the U-M in 1987. “Tachi was one of Michigan Medical School (UMMS) to the 1980s under the leadership of of my most influential mentors for since 2009. In recognition of his contributions to then-Division Chief TACHI YAMADA, international activities,” noted Dr. modernizing the Chinese medical train- CHUNG OWYANG, MD, succeeded MD, KBE. Dr. Yamada expanded Kolars, who has served as the first ing system, Dr. Owyang was awarded Dr. Yamada as Division Chief in 1990 144 the international dimension of the Senior Associate Dean for Education honorary professorships by more than and continued building internation- Division’s work, particularly with 10 top medical schools in China. He al collaborations. Dr. Owyang has Japan, increasing exchanges among served as Chair of the AGA International helped train a generation of academic learners and teachers at U-M and Committee for two terms (1995 to gastroenterologists in China and abroad. Many of Dr. Yamada’s former 1998, 2003 to 2006). During this time, made significant contributions to Japanese trainees have gone on to he initiated the first AGA meeting in medical training and the teaching of become leaders in gastroenterology. Asia to promote cross-cultural interac- clinical practice in China, Singapore Dr. Kentaro Sugano is the Chair of tion. This meeting continues to rotate to and Thailand. He played a key role in Medicine at Jichi Medical University in J a different Asian country every year. As os helping to develop China’s first MD/ ep Japan, and Dr. Tsutomu Chiba is now Chair of the AGA China Task Force, Dr. h PhD program at Jiao Tong University Kola rs, MD Chair of Medicine at Kyoto University. Owyang developed a 10-year blueprint
Tachi Yamada, MD, KBE Gastroenterology and Hepatology faculty from Peking University and the University of Michigan orations, including through Global Joint Institute investigations include REACH, a global UMMS initiative led the effects of diet on irritable bowel by Dr. Kolars to develop people and syndrome, the role of the microbi- programs that improve health and ome on dysmotility syndromes and healthcare through international development of biomarkers for partnerships. the diagnosis and management of hepatoma. Researchers also are jointly Amplifying Clinical and comparing and contrasting the natural Translational Research through course of viral hepatitis, which has a Collaboration higher disease burden in China. Chung Owyang, MD Dr. Kolars co-founded and co- “These joint projects are so successful 145 directs the University of Michigan for AGA initiatives in China. In 2015 Dr. because they build upon synergies and Peking University Health Owyang, together with Dr. Gary Wu, between the two institutions,” said Dr. Science Center Joint Institute organized the first joint meeting with Kolars. “Through the Joint Institute, for Clinical and Translational American and Chinese IBD experts in investigators can leverage shared Thailand: Training medical Research (puuma.org), launched with the Gastroenterological Associ- Beijing. This meeting explored factors resources, including funding, patient students and fellows in 2010. Gastroenterology faculty ation of Thailand (GAT). At the time, contributing to the alarming increase volumes and increased access to new Pinit Kullavanijaya, MBChB, DTM&H, Gastroenterology from both institutions and their In the early 1990s, Dr. Owyang and of IBD in Asia ( , 2016, technologies and therapies. It’s a win- PhD, then-professor of gastroenterol- affiliated hospitals collaborate on a Dr. Yamada—then serving as president in press). win that creates many opportunities ogy at Chulalongkorn University, was broad range of important clinical GI of the American Gastroenterological for mutual learning and discovery.” serving as president of the GAT. Other Division faculty are involved in research projects. Association—organized a joint meeting many additional international collab- Since that meeting, the U-M GI ological field generally in Thailand,” and fellowship training programs so The team has conducted in-country Division has maintained close ties said Dr. Kullavanijaya. that fellows can gain GI training in teaching and brought teachers from with the Chulalongkorn University their home country. Ethiopia to U-M to train in new edu- In recognition of Dr. Owyang’s GI unit. Second-year fellows from the cational methods and helped them role helping to develop academic HARI CONJEEVARAM, MD, MSc, CU GI unit come to Ann Arbor to train set up a new Fellowship Training gastroenterologists in Thailand, he director of the U-M GI Fellowship with U-M GI faculty during four-week Program in Gastroenterology. A novel was elected an honorary fellow of Training Program, and colleagues electives. Other fellows from Thailand teleconference program enables Thailand’s Royal College of Physicians currently are developing curricula can spend between one and three fellows and teachers in Ethiopia to in 2011. In 2015, he was honored and educational models for Ethiopia. years training in research and con- participate in the U-M GI division’s by His Excellency Pisan Manawapat, ducting clinical observation. Many conferences. In addition, GI fellows Thai Ambassador Extraordinary and trainees have gone on to become full will come to U-M and U-M GI fellows 146 Plenipotentiary to the United States. professors and now hold leadership will also have the opportunity to positions at universities and hospi- Ethiopia: Strengthening rotate in Ethiopia. tals throughout Thailand. academic medical systems “We’ve been sending our faculty Although Ethiopia’s population and fellows to the U-M GI Division tops 90 million, the country is for more than two decades now, home to only a small number of and it has benefited not only the gastroenterologists. The U-M GI Chulalongkorn University GI Unit division is helping to change that by specifically but also the gastroenter- Dr . Owyang with Thai co-developing new medical school Ambassador His Excellency Hari Conjeevaram, MD, MSc Pisan Manawapat and his wife, Wanchana Manawapat India: Developing tertiary Taken together, these and other new “When you think about the impact of clinical delivery programs programs have amplified the U-M the Division’s global efforts, it’s much GI division’s impact on health and greater than the impact of specific Dr. Conjeevaram and colleagues also healthcare globally. Dr. Kolars credits activities,” he said. “ A lot of the global have facilitated rotations for U-M GI the Division with inspiring his own health programs I’ve developed got fellows in India, where he has worked leadership and vision for creating their footing from my early work in the with local healthcare providers to and directing medical training and Division with people like Dr. Owyang establish a free GI clinic and GI endos- health system development pro- and Dr. Yamada. There is a trickle- copy unit. In collaboration with the grams to improve global health. down effect because of the ways the All India Institute of Medical Sciences Division nurtures these connections in New Delhi, he and colleagues across borders.” from the U-M Department of Internal 147 Medicine are working to develop tertiary-care clinical delivery programs, including programs to address an evolving clinical problem and growing epidemic: fatty liver disease. In 2014, Dr. Conjeevaram took a two-month sabbatical to visit academic institu- tions in India to educate trainees and explore future collaborative research and learning exchange programs.
Gastroenterology and Hepatology faculty from St . Paul’s Hospital Dr. Conjeevaram with GI and Hepatology fellows from the All India Millennium Medicine College Addis Ababa, Ethiopia (top) and faculty Institute of Medical Sciences, New Delhi, India. from the St . Paul’s Hospital and the University of Michigan (bottom) . 148 Recognition + Awards: HONORING THE LEADERS AND BEST 149 Honoring the Leaders and Best
Faculty members of the Division of Gastroenterology and Hepatology have been widely Distinguished Mentor Award AGA Foundation for Digestive recognized for their service, leadership and notable scientific, clinical and educational This accolade is given to an individual Health and Nutrition achievements, earning many accolades over the years . for achievements as an outstanding Outstanding Women in Science mentor over a lifelong career. Award AWARDS American Gastroenterological Distinguished Clinician Award M. BISHR OMARY, MD, PhD This tribute honors women who have Association The Clinician Award honors practicing (2015) American Association for the CHUNG OWYANG, MD made outstanding contributions to Julius Friedenwald Medal physicians who bring scientific (2011) Study of Liver Sciences TADATAKA (TACHI) YAMADA, MD the field of digestive disease science The Julius Friedenwald Medal is knowledge and inquiry to bear on the Distinguished Service Award through clinical education, scholarship, the highest honor the AGA awards. art of medicine and care of patients. (2010) ANNA S. LOK (2011) research and patient care. Established in 1941, it recognizes an WILLIAM D. CHEY, MD (2015) Distinguished Achievement ANNA S. LOK, MD (2008) individual for lifelong contributions to GRACE ELTA, MD (2013) Award in Basic Science American Digestive Health JUANITA L. MERCHANT, MD, PhD 150 Foundation the field of gastroenterology and service TIMOTHY T. NOSTRANT, MD (2012) This award honors a senior investigator to the association. whose accomplishments in basic (2008) Joseph B. Kirsner Award Distinguished Educator Award CHUNG OWYANG, MD (2013) research have significantly advanced for Clinical Research in Established in 1987, this award American Liver Foundation TADATAKA (TACHI) YAMADA, MD the science and/or practice of Gastroenterology recognizes a person’s achievements as Distinguished Scientific (2003) gastroenterology, including hepatology. CHUNG OWYANG, MD (1995) an outstanding educator over a lifelong Achievement Award JOHN A. WILLIAMS, MD, PhD Hugh R. Butt Award for William Beaumont Prize career. ANNA S. LOK, MD (2008) (2014) Distinguished Achievement in This prize is bestowed upon JOSEPH KOLARS, MD (2014) JUANITA L. MERCHANT, MD, PhD Hepatitis B Foundation Clinical Research in Hepatology an individual who has made a JOHN DEL VALLE, MD (2012) Distinguished Scientist Award ANNA S. LOK, MD (1996) unique, outstanding contribution (2017) ANNA S. LOK, MD of major importance to the field of (2008) gastroenterology. ANNA S. LOK, MD (2016) HONOR SOCIETIES—MEMBERSHIPS National Academy of Medicine LEADERSHIP American Neurogastroenterology DEPARTMENT OF INTERNAL JOHN CARETHERS, MD and Motility Society (ANMS) MEDICINE AWARDS Association of American American Association for the JUANITA MERCHANT, MD, PhD CHUNG OWYANG, MD Physicians Members Study of Liver Sciences Clinical Excellence Society President (2000–2004) JOHN CARETHERS, MD ANNA S. LOK, MD WILLIAM HASLER, MD JOHN W. WILEY, MD (2016) ANNA S. LOK, MD President (2017) PETER HIGGINS, MD, PhD, MSc President (2014–2016) JUANITA MERCHANT, MD, PhD (2016) M. BISHR OMARY, MD, PhD American Gastroenterological JOHN DEL VALLE, MD (2015) CHUNG OWYANG, MD Association ROBERT FONTANA, MD (2015) TADATAKA YAMADA, MD WILLIAM D. CHEY, MD (2014) American Society for Clinical President (1996) ERIK-JAN WAMSTEKER, MD (2014) Investigation JOHN I. ALLEN, MD GRACE ELTA, MD (2013) 151 JOHN CARETHERS, MD President (2015) ANNA S. LOK, MD (2013) JOHN Y. KAO, MD TIMOTHY T. NOSTRANT, MD (2013) JUANITA MERCHANT, MD, PhD American Society for M. BISHR OMARY, MD, PhD Gastrointestinal Endoscopy (ASGE) Paul de Kruif Lifetime CHUNG OWYANG, MD GRACE ELTA, MD Achievement Award ELIZABETH SPELIOTES, MD, PhD, President (2007) CHUNG OWYANG, MD (2016) MPH KEITH S. HENLEY, MD (2009) ANDREA TODISCO, MD THOMAS WANG, MD, PhD JOHN WILLIAMS, MD, PhD Editorships
M. BISHR OMARY, MD, PhD, Chair KAO, RICHARD MOSELY, JOEL from 2010 to 2015. The Red Journal an unmet need for clinicians and of the Department of Molecular RUBENSTEIN, PHILIP SCHOENFELD, has an Impact Factor of 10.383 and is scientists by welcoming novel case and Integrative Physiology and THOMAS WANG and JOHN KAO the leading clinical journal covering series and cohort studies, early- the H. Marvin Pollard Professor of (Gastroenterology), JULIE DOUGLAS gastroenterology and hepatology. phase clinical trials and translational Gastroenterology, served as Editor- (Human Genetics) and CATHIE The AJG provides practical and research with clear applications to in-Chief for Gastroenterology from SPINO (Biostatistics) also played key professional support for clinicians human physiology or disease. In 2011 to 2016. Under his capable roles as special section editors. dealing with the gastroenterological 2016, CTG achieved an impact factor leadership, the Impact Factor moved disorders seen most often in patients. of 3.472. Gastroenterology has continued from 11.7 in 2011 to 18.2 in 2016. Many of the important guidelines to be the premier journal in the Many U-M GI faculty, together with for our practice are published in the field of digestive health and faculty from Pathology, Physiology journal. GI faculty who served as 152 disease, delivering up-to-date and and Surgery, served on the board of associate editors include DRS. HARI authoritative coverage of basic editors including Senior Associate CONJEEVARAM, PETER HIGGINS and clinical gastroenterology and Editors DRS. JOHN CARETHERS and and JAMES SCHEIMAN. hepatology. It was a huge honor CHUNG OWYANG, and Associate and a pleasure for the GI division at Dr. Chey was the founding co-Editor- Editors DRS. WILLIAM HASLER, Michigan to be the home for the top in-Chief of Clinical and Translational MALCOLM LOW, ASMA NUSRAT, journal in our field. Gastroenterology (CTG), a peer- LINDA SAMUELSON, DIANE reviewed open-access online journal SIMEONE and JOHN WILLIAMS. In WILLIAM D. CHEY, MD, served as dedicated to innovative clinical work addition, JOHN DEL VALLE, GRACE co-Editor-in-Chief of the American in the field of gastroenterology and ELTA, ROBERT FONTANA, JOHN Journal of Gastroenterology (AJG) hepatology. CTG was created to fill 153
M . Bishr Omary, MD, PhD William D . Chey, MD 154 Friends + Donors 155 Making a Difference for Others: NEW GI INNOVATION FUND SUPPORTS ADVANCES IN MEDICINE
In 2013, Mary Petrovich turned 50. She competed in her second U.S. Women’s Amateur (golf) going on within the Division and Championship, where she made match play and finished in the top 25. A few days after the the U-M Medical School, including event, she had her first screening colonoscopy. many collaborative efforts combining medicine, engineering and other But during the procedure Mary’s next six months to try to resolve Mary’s answer was to find a way to disciplines pursuing biomedical colon was perforated. Her fast-paced complications. advance promising innovations in research. life as private equity entrepreneur, medicine, and she established the A University of Michigan engineering mother to two teenagers and Gastrointestinal Innovation Fund at Projects supported by the Fund alumna with an MBA from Harvard, nationally competitive golfer U-M to do just that. already are underway, including Mary analyzed her experience. was upended, and several related to the use of predictive “Being an engineer, I began thinking The GI Innovation Fund supports she underwent tools to identify which individuals through the failure modes, what discovery and development of 156 several might benefit the most from happened to me and how it could technologies to improve care surgeries colonoscopy and ways to improve have been avoided.” of patients who suffer from over procedure-related safety. gastrointestinal disease. The fund will the She also asked herself two questions support early-stage research, with a In spite of her own difficult that will undoubtedly have a particular focus on technologies that experience, Mary sees opportunity. As tremendous impact on the lives of could lessen the need for invasive she told GI division faculty, staff and others: “What can I do now to make procedures. friends during the 75th Anniversary sure this happens to no one else, and Symposium, “I’m thrilled to help make what can I do to take this misfortune Mary was motivated to create the GI a difference with you for others.” and turn it into opportunity?” Innovation Fund at the U-M because of the “cutting-edge” work she saw
ich Mary Petrov Donor Honor Roll
Gifts from individuals, foundations and corporations enable the Division of Gastroenterology Pfizer, Inc. to train the world’s best physicians, provide exemplary patient care and to conduct innovative AstraZeneca Pharmaceuticals LP research . This list acknowledges individuals who made outright gifts, new pledges, pledge Robert Wood Johnson Foundation payments and planned gift including bequests of $1,000 through November 2016 . Eli and Edythe L. Broad Foundation Dr. Kamal Gupta and Dr. Nisha Gupta $1,000,000 and above $100,000 to $499,999 Mr. and Mrs. Roy H. Henley Novartis Pharmaceuticals Corporation Johnson & Johnson Shirley M. McLaughlin Trust American Gastroenterological Juvenile Diabetes Research Foundation Glaxo Wellcome, Inc. Crohn’s & Colitis Foundation Association Foundation International Novartis of America, Inc. American Diabetes Association, Inc. Anonymous Donor American Association for Doris Duke Charitable Foundation American Gastroenterological Novartis US Foundation Cancer Research, Inc. Mr. and Mrs. Charles J. Andrews Association Sandoz Research Institute Mr. Edward Ravitz* 157 TUKTAWA Foundation GlaxoSmithKline Mr. Kevin Cheng Zou Bristol-Myers Squibb Company Dr. Chung Owyang and The National Pancreas Foundation $500,000 to $999,999 Thomas H. C. Cheung Foundation Mrs. Jeannette Owyang March of Dimes Birth Defects Limited The Damon Runyon Cancer Research Foundation Metropolitan Detroit American Association for the Study Mr. and Mrs. John S. Dobson* Foundation Division of Liver Diseases Dr. Timothy T. Nostrant * and Ms. Carol L. Osmer Janssen Pharmaceuticals, Inc. Foundation for Digestive Health Mrs. Cynthia A. Nostrant The American Society for Dr. Henry Van Dyke and and Nutrition Hoffman-La Roche Ltd Gastrointestinal Endoscopy Dr. Rebecca W. VanDyke American Digestive Health Rose and Lawrence C. Page, Sr. Family Dr. Keith Henley* and Rockefeller Brothers Fund Foundation Charitable Foundation Mrs. Marcelle Henley* SmithKline Beecham Corporation Mr. and Mrs. Scott W. Petrovich Schering-Plough Research Institute The Ravitz Foundation $100,000 to $499,999 Eli Lilly and Company $10,000 to $49,999 Blowitz-Ridgeway Foundation Ms. Francesanna Sargent The American College of Mr. Robert Cook* and Mrs. Jane E. Cook Dr. and Mrs. John M. Carethers Sondoz Forschungsinstiut Chaffin Luhana, LLP Gastroenterology Allergan Pharmaceuticals Mr. and Mrs. Anthony J. Procassini Mrs. C.K. Hui Ms. Judith Sutherland The Greenwall Foundation Anonymous Donor Dr. Dale R. Bachwich and Ms. Pearl Hui National Organization for Rare Blue Cross Blue Shield of Michigan Dr. and Mrs. John C. Byrd Dr. Vera O. Kowal Mr. and Mrs. William Hui Disorders Rome Foundation for Disorders of Dr. and Mrs. Shoou-I Wang Central Society for Clinical Research Mr. and Mrs. David Kwan Merck & Co., Inc. Gastrointestinal Function Carter-Wallace Pharmaceutical, Inc. Ms. Ann Hunter Taisho Pharmaceutical Co., Ltd. Inflammatory Bowel Disease Working Solvay Pharmaceuticals Centocor Ortho Biotech Dr. Baldev K. Malik and The Hartwell Foundation Group (IBDWG) Galecto Biotech Dr. and Mrs. Tadataka Yamada Dr. Shashi K. Malik Pharmacia and Upjohn, Inc. $50,000 to $99,999 Janssen Pharmaceutical Research Attenuon, L.L.C. Dr. Joel Montbriand Abbott Laboratories Cystic Fibrosis Foundation National Foundation Dr. Steven L. Carpenter and Stromedix, Inc. 158 Juvenile Diabetes Foundation-Canada Headquarters P&G Company Ms. Deborah Carpenter Sucampo Pharma Americas, Inc. Chemtrak Dr. Anna S. Lok Searle Research & Development Mr. Sheng Peng Wei The Gralnick Foundation Community Foundation for Southeast Mr. and Mrs. Theodore J. Green Covance Mr. Melvin Logan Michigan Greenview Foundation Hepatitis C American Society of Transplantation Hoechst Marion Roussel Mr. and Mrs. Mitchell T. Danzig Research Fund Global Probiotics Council Amgen Inc. Kinexis, Inc. Ms. Lorilee Babb* Metabolic Solutions Mr. and Mrs. James A Kennedy* Integrated Therapeutics Mr. Alexander Wong American Neurogastroenterology Elizabeth E. Kennedy Fund Ms. Youngsim L. Oh Boston Research & Development Mr. Donald Osmer Byk Gulden Lomberg Chemische Fabrik Corporation Procter & Gamble Company GmbH Dr. and Mrs. John W. Wiley Mr. Gary L. McKay $5,000 to $9,999 Dr. Matthew J. DiMagno and Mandarin Theaters Corporation $1,000 to $4,999 Kopel Kahn Trust Dr. Monica M. Dimagno Dr. and Mrs. Jorge A. Marrero Reid-Rowell The Shaw Foundation Shaw Movie City Hong Kong Limited Mr. Mark C. Bander and Dr. Hui Wai Mo Dr. Gary D. Wu Dermatology Foundation Robert J. and Carolyn L. Phelps Mrs. Kathleen A. Bander Peyser Foundation for Population Mr. Daniel G. Wyllie and Boston Scientific orporationC Foundation, Inc. Marion Laboratories, Inc. Health Ms. Patricia A. Wyllie Nestle Axcan Pharma Inc. GlaxoSmithKline Dr. James Y. Rhee Mr. Chien-Nan Yang and Mrs. Lillian E. Glanz Fujisawa Pharmaceutical Co. Ltd. G.D. Searle Charitable Trust The DS Foundation Mrs. Jia-Chyi Chiu American College of Surgeons Fujisawa USA, Inc. Searle Laboratories Division G. D. Searle Mr. and Mrs. John G. Searle* Dr. Robert and Mrs. Janet M. Miller Ms. Rhonda Amber Dr. Marigowda Nagaraju & Company The Society for Biomolecular Sciences Damer & Cartwright Sylvia Weider - Amber Family Focus Medical Communications, LLC Dr. John Allen and Ms. Carolyn Allen Dr. and Mrs. William M. Tierney Associate Dean and Foundation Quintiles Amersham-Searle Corporation Professor Joji Utsunomiya Mrs. Joseph C. Kolars Calypte Biomedical Company Wyeth Pharmaceuticals 159 Ballard Medical Products Dr. Richard T. Wille and Dr. James M. Scheiman SmithKline Beecham International Medical College of Ohio at Toledo Betty McDonald Smith Trust Ms. Debra R. Wille Mr. Michael A. Baskin Dr. and Mrs. William D. Chey TAP Pharmaceutical Products Inc. Dr. and Mrs. Bahri M. Bilir Agilent Technologies Dr. Michael E. Elta and Dr. Grace H. Elta Pharmaceutical Product Development, Mr. Bharat N. Desai and Mr. and Mrs. Sherwood M. Ortho Pharmaceutical Corp. Inc. Ms. Neerja Sethi Boudeman Mr. and Mrs. Kopel I. Kahn Mallinckrodt Pharmaceuticals Dr. Pauls Low FODMAP Foods, LLC Dr. Luke T. Evans Mr. and Mrs. Arthur A. Da Silva Winmex Investments Limited F.O.M.A.P.I. Mr. and Mrs. Michael G. Ford Dr. Philip S. Schoenfeld Dr. Gary W. Falk and Dr. Adam B. Gorelick and Dr. and Mrs. Peter D. Higgins Dr. Stewart C. Wang and Dr. Grace L. Su Ms. Lynn K. Shesser Dr. Judith L. Gorelick Integrated Communications Corp. Celanese Corporation Mr. Richard A. Humphreys Mr. and Mrs. Robert K. Hutton Ms. Lisa S. Sylvest Mr. Law Ka Kui Mr. K. S. Mahindru $1,000 to $4,999 Mr. Erick Kwok and Dr. Jeffrey S. Sams and Ms. Phyllis Glanz and Mr. Peter J. Dilworth and Ms. Chan Y. May Dr. Linda J. Hall Ms. Sara Mayes Ms. Gwynneth Newton Dr. Arnold J. Markowitz and Ms. Dawn Mr. and Mrs. Christopher P. Dr. Kenneth S. Lown and Dr. and Mrs. William E. Knecht Donaldson, Lufkin & Jenrette, Inc. S. Markowitz Legghio Dr. Deborah A. Lown Dr. and Mrs. Manus L. Krasman Mrs. Catherine A. Fox Dr. Cyrus R. Piraka Dr. Erikjan Wamsteker and Dr. Thomas M. Shehab and Dr. and Mrs. Michael R. Lucey Mr. Herman Frankel and Fraternal Order of Eagles – Social Fund Dr. Eve D. Losman Dr. Joslyn M. Shehab Dr. Jean P. Raufmann Ms. Sharon Frankel Cytel Dr. Dongxia Lu and Mr. Jianmin Yi Dr. and Mrs. Jeffrey D. Stahl Ms. Jennifer M. Thomas-Goering Dr. Puneet Garg and Dr. Ira Gantz Mrs. Carol S. Mallory Dr. and Mrs. James P. Symons Dr. Wilfred Lee Dr. Pratima Sharma Ms. Laurie B. Glanz Dr. and Mrs. John C. Rabine Boeing Company Dr. and Mrs. Robert J. Fontana Mr. Bruno Garlepp Procter & Gamble Pharmaceuticals Dr. Wei M. Sun and Ms. Poh Toe Dr. and Mrs. C. Richard Boland Dr. and Mrs. Michael W. Dr. and Mrs. Bal K. Gupta Dr. and Mrs. Sami R. Achem Dr. Naoky Tsai Dr. Jeffrey L. Barnett and Mulholland Dr. Michael Heidenreich and 160 Axcan Pharma U.S., Inc. Dr. Rex T. Wang Ms. Laurie C. Barnett Pfizer oundationF Dr. Katherine D. Heidenreich Mr. Phil N. Banks Wilson-Cook Medical Dr. Yuen Kwok Yung and Dr. Thomas J. Alexander HFF Foundation Gilead Sciences, Inc Dr. Wen Yi Wu Ms. Louisa W. S. Lee Dr. Rajiv Bansal and Dr. Robert C. Hyzy Huron Gastroenterology/Center for Mr. Guilano Schiozzi and Ms. Evelyn E. Clark and Dr. Mimi G. Bansal Mr. Gene K. Lee and Digestive Care Mrs. Denise Zamiello-Schiozzi Mr. Paul Clark Mr. Edward H. Bardeleben and Ms. Soon A. Lee Dr. Jessica P. Hwang and Mr. Jeffery R. Holden and Dr. Gregory M. Christman and Ms. Linda K. Bardeleben Dr. and Mrs. James A. Leonard, Jr. Mr. Brent J. Hwang Ms. Teresa Casey Dr. Ellen M. Zimmermann Beckman Instruments, Inc. Dr. Nancy Leung J.B. Lippincott Company Dr. Richard S. Kwon and Mr. Robert and Dr. and Mrs. Douglas H. Blanks Mr. William J. Lichtenberger Dr. and Mrs. Srinivas K. Janardan Dr. Hellan Kwon Mrs. Lori Hirshman Ms. Christine M. Brozo Dr. and Mrs. Paul R. Lichter Dr. Betty F. Kim Dr. and Mrs. Stanley R. Strasius Mrs. Minakshi Nag Dr. and Mrs. Michael E. Cannon Dr. Stacy B. Menees Dr. Laurel R. Fisher Dr. and Mrs. Henry D. Appelman Metropolitan Eye-Care Physicians, Mr. Eric M. Quist and Dr. Mark A. Stern Professionalcorp. Ms. Gina Quist Mr. Douglas Strayer NABI, Inc. Mr. Gene Richards and Mr. Michael P. Tacey Dr. Carroll M. Leevy* Ms. Rosemary E. Richards Ms. Sharon Vanderwall Naus, Ltd. Dr. Raf S. Rizk Ved P. Singla Trust Dr. Kimya L. Nguyen Rowell Laboratories, Inc. Dr. and Mrs. Thomas D. Wang Mr. and Mrs. Bruce Osani Ms. Julie Woodward Hyzy Mrs. Cathy Dunn* Mr. and Mrs. Donald E. Petersen S.P. Garg, MD, P.C. *Deceased Phase Five Communication Inc. Dr. Steven Scaglione and Ms. Sheila Eswaran 161 The Division of Gastroenterology greatly values our donors, and we have made every effort to ensure the accuracy of the honor roll . Please call us at 734-763-5999 if you note any errors . 162 Poised for Growth 163 The Future of Gastroenterology: THE CENTER FOR DIGESTIVE AND LIVER HEALTH
The practice of gastroenterology and hepatology has changed dramatically since the founding of the Division 75 years ago. Advances in molecular biology, genetics, biochemistry, innovative imaging techniques and bioinformatics have contributed to an explosion of new scientific information that has fundamentally changed the way we diagnose, treat and prevent disease . The Division, with its talented inves- Advances in genomics, epigenomics, on proliferation, differentiation tigators and masterful clinicians, is proteomics, microbiomics, metag- and apoptosis,” initiated by DRS. RESEARCH PROGRAMS well prepared to explore unparalleled enomics and metabolomics have MERCHANT, SAMUELSON and opportunities and address new chal- significantly altered our concept of dis- GUMUCIO in 2003 paved the way Stem Cell Biology • lenges to improve our understanding ease pathogenesis and have opened a for our stem cell biology research • Gut Microbiome of complex disease processes. As we portal for formulating new treatments program. The recent establishment of 164 work to devise new approaches to for challenging GI disorders. the organoid program by DR. JASON Epigenetics • disease treatment and prevention, the SPENCE allows investigators to In the next 10 years the Division will Genomic Medicine Division remains steadfast in its pur- grow intestine as three-dimensional • focus on four major themes: suit of its tripartite missions: research, structures from pluripotent stem clinical care and education. Stem cell biology continues to be cells and provides innovative tools to study stem cell interactions with the Research an area of emphasis of our research. Stem cells play a critical role in environment. Advances in medicine depend on maintaining normal tissue function The Division will continue to recruit the acquisition of new information and in the development of cancer physician scientists with expertise in through research, and the third mil- and degenerative GI disorders. The stem cell research and expand upon lennium ushers in the era of “omics.” program project, “Cellular decisions this program to explore the emerging disease (IBD), irritable bowel syndrome gut dysbiosis are beginning to lay the FLD). This information also provides role of stem cells in the treatment of a (IBS) and metabolic disorders. foundation for forming an Epigenetic novel targets for intervention and variety of GI disorders. Research Program in the GI Division. prevention. Under the leadership of The Division is fully committed to Dr. Speliotes, the Genomic Medicine The recently initiated Gut Micro- expanding the Epigenetics Program, The Genomic Medicine Program PROPOSED CENTER Program will continue to grow. biome Project, initiated by DRS. recently initiated by DR. JOHN WILEY. allows physicians to develop targeted FOR DIGESTIVE AND VINCENT YOUNG, JOHN KAO and Basic and clinical studies indicate that approaches to the treatment of GI Clinical Care LIVER HEALTH CHUNG OWYANG, will continue to alteration in gene function can occur disorders. The completion of the We take pride in our multidisciplinary • Improve the patient expand. Advances in DNA sequencing without changes in DNA sequence. This Human Genome Project provides new approach to care for patients with experience technology combined with new bio- may occur through DNA methylation, opportunities to pursue personalized complex GI issues. This includes our computational tools enable scientists histone modification and chromatin medicine. Gene expression profiles • Allow for growth of IBD, IBS and pancreatic and biliary to describe our microbial environment remodeling. Epigenetic alterations are may be used to guide therapy and Digestive and Liver Health 165 disorders clinical programs. with greater precision. The genomic associated with a number of chronic inform prognosis for a variety of dis- Programs In the coming year, we plan to use revolution offers an exceptional disorders including GI cancers, aging, orders. In fact, the use of genotyping a similar blueprint to establish a • Increase the presence of may provide a new way to assess opportunity to identify the molecular degenerative diseases, chronic pain non-alcoholic steatohepatitis U-M within the local and mechanisms governing commensal syndromes and eating disorders. the risk of certain diseases as well (NASH) Multidisciplinary Program national communities host-bacterial relationships. This knowl- as variation in response to different The groundbreaking work of Dr. Wiley at the University of Michigan. edge helps us understand how such drugs. Research from DR. ELIZABETH • Support GI education and on epigenetics pathways in stress NASH is the most common liver interactions contribute to normal phys- SPELIOTES sheds light on the role of research and abdominal pain and DR. JOHN disease in the United States and is iology and provides the foundation certain genes in the causality of com- KAO’S research on epigenetic alter- predicted to become an increasingly necessary to formulate normal thera- mon conditions such as obesity and ation of the gut immune system in important cause of liver-related peutic strategies in inflammatory bowel non-alcoholic fatty liver disease (NA- morbidity and mortality. Metabolic chronic GI disorders. The Division multidisciplinary care in a state-of-the- Education changes associated with obesity are will focus on the development of a art environment. The proposed facility Training the next generation of the predominant drivers of NASH. GI Telemedicine Program. This would comprise 200,000 sq. ft. and gastroenterology leaders is a major Although pharmacotherapy for NASH will further contribute to improved include a 12- to 14-room endoscopy mission of the Division. The University is an active area of translational accessibility and lessened chronic suite, 40 exam rooms, dry lab space, a of Michigan is recognized both for its research and clinical trials, there are burden for patients who have to travel call center, conference rooms, auditori- clinical training as well as for its top- currently no FDA-approved therapies. long distances to our Medical Center um, pharmacy and a test kitchen. ranked training in basic science and However, clinical studies suggest for their clinical care. At the same time, With the CDLH, the Division will be outcomes and health service research. modest weight loss may result in the Telemedicine Program will facil- able to provide clinical services in one The rapid advances in molecular histological improvement in NASH. itate efficient resource utilization for location, with multiple specialties biology, biochemistry and genomics Hence, we propose the development the Medical Center while enhancing 166 under one roof, to foster collaboration has significantly altered the way we of a multi-interventional weight loss continuation care and followup, lead- and communication. By adding the practice medicine. As a result, the Divi- program for NASH treatment. This ing to improved clinical outcomes. space, the Division will be able to ex- sion is revamping its core curriculum will involve lifestyle modification, To enhance our clinical growth and pand clinical and endoscopic activity, to include findings garnered from this nutrition education, fecal transplant improve the patient experience and developing an innovative food-centric explosion of scientific information so and bariatric endoscopic and surgical clinical outcomes, the Division pro- program and telemedicine infrastruc- that our trainees become familiar with intervention. poses the development of a Center ture. The proposed CDLH will help the fields of genomics, epigenomics, The increasingly popular utilization of for Digestive and Liver Health to facilitate clinical trials and offer proteomics and bioinformatics in telemedicine heralds great promise (CDLH). The Center, conceptually personalized medicine and health order to integrate scientific advances in the field of gastroenterology, similar to the U-M Cardiovascular service research. into their clinical practice. especially in treating patients with Center, would provide coordinated, The Division takes an individualized in career planning, financial and training approach to bring out the practice management, organizational best in each trainee. We will continue leadership and healthcare policy. to diversify our training to include It will draw upon the University’s novel programs, including the Na- wealth of resources and expertise in tional Clinician Scholar Program and business administration, healthcare Graduate Medical Education Scholar management, public policy and Program to train clinical educators and clinical intervention. GI FELLOWSHIP PROGRAM the Innovation and Entrepreneurship Physician Scientist Training Program Since its founding 75 years ago, • Program to train physicians interested the Division has become one of the in translating scientific findings into • Outcome Research Training Program nation’s preeminent centers for the 167 clinical products. prevention, diagnosis and treatment • National Clinician Scholar Program Under the leadership of DR. JOHN of disorders of the digestive tract • Graduate Medical Education Scholar Program ALLEN, the Division is developing and liver. We are proud of our past a business and leadership training achievement and optimistic about • Innovation and Entrepreneurship Program program, which will allow trainees shaping the future. With our com- to obtain a master’s degree in mitment to scientific discovery and business administration. The new the clinical excellence of our faculty program is tentatively named, and trainees, we will remain “always “Life, Leadership, and Legacy” healing, forever valiant.” and will educate interested fellows 168 Celebrate! 169 GI and Hepatology at the University of Michigan: PAST, PRESENT AND FUTURE OF INNOVATION, CLINICAL PRACTICE AND LEADERSHIP
In September 2016, the Division of The Friday program, moderated by What’s Next for GI—The Red Gastroenterology and Hepatology Dr. Juanita Merchant, showcased the Queen celebrated the 75th anniversary of the achievements of some of our own Current changes in healthcare delivery founding of the Division. As part of that U-M faculty, including Drs. Anna Lok, and payment will test the strength and celebration the Division held a two-day Liz Speliotes, John Allen, John Wiley, creativity of health systems including symposium, “GI and Hepatology at Peter Higgins, William Chey, Hari the University of Michigan. We will the University of Michigan: Past, Conjeevaram, Thomas Wang, Jason feel like the Red Queen from Alice in Present and Future of Innovation, Spence and Nobu Kamada. Mary Wonderland, who said we must run as Clinical Practice and Leadership.” Petrovich, a philanthropist and friend fast as we can to stay in one place—twice to the Division, was also on hand to The Thursday program, moderated as fast to move ahead. Health systems give her personal reflection on patient 170 by Drs. Chung Owyang and that can coordinate care and learn how care and the future of innovation. William Chey, included Dr. John JOHN I. ALLEN MD, MBA, AGAF to care for high-cost patients in the Carethers, followed by leaders in On Friday, Medicine Grand Rounds Professor of Internal Medicine; most efficient manner with the highest gastroenterology and hepatology was presented by a special guest, Dr. Professor of Gastroenterology quality will emerge as strong leaders. from across the nation including Drs. Daniel K. Podolsky, President of UT Division of Gastroenterology and That is our intention here. Tachi Yamada, Rick Boland and David Southwestern Medical Center. Hepatology Lieberman. Distinguished alumni University of Michigan Medical School speakers included Drs. Ezra Burstein, C Joseph Elmunzer, Michael Kochman, h un Uri Ladabaum, John Inadomi and g O wya Michael Lucey. ng, MD The University of Michigan addition to building a robust clinical Fellowship Program Experience with the Low-FODMAP infrastructure to provide holistic, The GI fellowship program at the diet integrated care to patients with IBS University of Michigan has enjoyed and other GI disorders, DDNLP will It is increasingly clear that a rich history and the program conduct cutting-edge translational nutrition plays a pivotal role in the today is quite robust. The program and clinical research and create pathogenesis and treatment of many highlights include many educational, unparalleled training opportunities for gastrointestinal disorders. At present, research and innovative projects, physicians and allied health providers. the best evidence supporting dietary with new programs in development, therapies exists for the irritable bowel to train the next generation of syndrome (IBS). Food can trigger gastroenterologists. IBS symptoms through direct and 171 WILLIAM CHEY, MD, FACG, AGAF indirect effects on motility, visceral HARI CONJEEVARAM, MD, MSc Timothy Nostrant Collegiate Professor sensation, brain-gut interactions, gut Professor of Medicine of GI & Nutrition Sciences; President, microbiome, intestinal permeability Program Director, Gastroenterology Clinical Excellence Society; Director, and gut immune function. Recent Fellowship Training GI Physiology Lab; Director, Digestive randomized, controlled trials, University of Michigan Medical School Disorders Nutrition & Lifestyle including data generated at U-M’s Program; Medical Director, Michigan Digestive Disorders Nutrition & Bowel Control Program Lifestyle Program (DDNLP), support University of Michigan Medical School the efficacy of the low-FODMAP diet and gluten-free diet in IBS patients. In Machine Learning in A Battle Within: Competition Gastroenterology and Between Good and Bad Bacteria Hepatology in the Gut
Machine learning can identify patterns We found that inflammation-induced in laboratory data that can predict metabolic reprograming in E. coli disease progression and response to promotes the selective growth of medications. We have shown that this pathogenic E. coli at the expense of its is valuable for hepatitis C, prediction commensal counterparts. Depriving of success with thiopurines in IBD and pathogenic bacteria of preferred response to vedolizumab in ulcerative nutrients suppresses their ability to 172 colitis. bloom in the gut. PETER D. R. HIGGINS, MD, PhD, MSc NOBU KAMADA, PhD ANNA S.F. LOK, MD, FRCP Associate Professor of Medicine Assistant Professor, Gastroenterology Assistant Dean for Clinical Research; University of Michigan Medical School University of Michigan Medical School Alice Lohrman Andrews Research Professor of Hepatology; Professor of Internal Medicine and Director of Clinical Hepatology University of Michigan Medical School From Non-A, Non-B Hepatitis, Modeling Human Development Even though obesity and NAFLD are to Hepatitis C Cure, to Global Using Insights from Organoids epidemiologically highly related Elimination of Hepatitis C and Embryos to each other, genetics can point to distinct etiologies that can be There has been miraculous progress Dr. Spence presented work from his specifically targeted to aid in precision from non-A, non-B hepatitis—a term laboratory highlighting how they therapies for these conditions. coined for hepatitis C in the 1970s—to are implementing 3-dimensional discovery of hepatitis C virus in 1989 human pluripotent stem cell derived and the development of blood tests to intestinal organoids to investigate diagnose and screen blood products human intestine development, and to for hepatitis C in 1991, to the approval understand how microbes (bacteria) of combinations of oral antiviral that colonize the neonatal gut interact 173 agents that can achieve virologic cure JASON SPENCE, PhD with the intestinal epithelium, leading ELIZABETH SPELIOTES, MD, PhD, in more than 95 percent of patients Associate Professor of Internal Medicine, to enhanced intestinal maturation and MPH in 2014. The remarkable progress Gastroenterology; Associate Professor of function, or to epithelial damage and Associate Professor in hepatitis C has not been seen in Cell and Developmental Biology disease. University of Michigan Medical School any other field of medicine and has University of Michigan Medical School Genomics has identified that already translated to a decrease in susceptibility to becoming obese or number of patients listed for liver developing NAFLD lies in nervous transplantation. system genes/pathways and liver lipid/glucose metabolism respectively. Imaging the Serrated Pathway that altered gene expression involving for Colorectal Cancer epigenetic regulatory pathways may play an important role to explain why A targeted imaging method for these patients experience enhanced early detection and prevention of abdominal pain. colorectal cancer was presented using a fluorescence labeled peptide that binds specifically to overexpressed cell surface targets in sessile serrated adenomas.
174 THOMAS WANG, MD JOHN W. WILEY, MD H. Marvin Pollard Collegiate Professor Professor of Internal Medicine; of Endoscopy Research; Professor, Director, Michigan Clinical Research Internal Medicine, Biomedical Unit Engineering, Mechanical Engineering University of Michigan Medical School Chronic stress is associated with enhanced abdominal pain, particularly in patients with functional GI disorders such as irritable bowel syndrome. Recent evidence suggests 175 C. RICHARD BOLAND, MD, AGAF DAVID A. LIEBERMAN, MD EZRA BURSTEIN, MD, PhD BADIH JOSEPH ELMUNZER MD, STEVEN CARPENTER MD Emeritus Professor of Medicine Associate Professor of Internal MSc Academic Chair Professor of Medicine Chief, Division of Gastroenterology/ Medicine and Molecular Biology Associate Professor Department of Internal Medicine Baylor University Medical Center Hepatology Chief, Division of Gastroenterology / Peter B. Cotton Chair for Endoscopic Memorial University Medical Center, (BUMC), Dallas, Texas Oregon Health & Science University Hepatology Innovation Savannah, Georgia UT Southwestern Medical Center Department of Internal Medicine An Overview of the Discovery of Settled and Unsettled Issues in Managing Outpatient Clinical Medical University of South Carolina the Familial Colorectal Cancer 2016 Understanding Pathologic Issues In GI: An Evidence-Based Genes Inflammation and IBD in the Clinical Trials in GI Endoscopy Update Genomic Era 176 MICHAEL LEE KOCHMAN, MD URI LADABAUM, MD JOHN M. INADOMI, MD MICHAEL R. LUCEY, MD DANIEL K. PODOLSKY, MD Wilmott Family Professor of Medicine Professor of Medicine, Senior Vice Cyrus E. Rubin Endowed Chair in Chief, Gastroenterology and President, UT Southwestern Medical and Professor of Medicine in Surgery Chief Medicine Hepatology Center Director, Center for Endoscopic Director, Gastrointestinal Cancer Professor of Medicine and Head Professor of Internal Medicine Tale of the Vasa and the Future of Innovation, Research, and Training Prevention Program Division of Gastroenterology University of Wisconsin School of Academic Medical Centers Perelman School of Medicine Division of Gastroenterology and University of Washington Medicine University of Pennsylvania Hepatology Barrett’s Esophagus Liver Transplantation and Stanford University School of Medicine Incorporation of Innovation into Alcohol: an Uneasy Mix Gastroenterology: Moving the Risk Stratification in Colon Boundaries Cancer Screening 177 178 179 Dinner
As part of the Division’s 75th anniversary celebration, a celebratory dinner was held at the U-M’s Museum of Art. The beautiful surroundings, amazing food and captivating speakers made it a very special event.
180 181 Let’s Go Blue!
It wasn’t all lectures and grand rounds for 125 Symposium attendees. On Saturday, attendees could be found at a tailgate before proceeding on to the Big House, where they watched the Wolverines beat Penn State 49-10.
182 183 Colleagues, Alumni and Friends,
It is my great honor and pleasure to congratulate the Division of Gastroenterology and physicians and scientists. Over the past Hepatology on its 75th anniversary . 50 years, the Division of Gastroen- terology and Hepatology has trained The Division is one of the largest and ipated in 415 clinical studies, in many disorders in the field. In areas such as more than 400 gastroenterologists and most innovative academic gastroenter- cases gaining access to novel therapies bioinformatics, personalized medicine, hepatologists to be leaders in the field ology and hepatology practices in the available at few other institutions. epigenetics and multidisciplinary care, worldwide. United States, successfully delivering cross-functional collaborations are These innovations and breakthroughs outstanding care to patients across rapidly changing what will be possible To the Division’s dedicated faculty, staff have made it possible for our patients Michigan and beyond. In 2016, the in the future of gastrointestinal care. and leadership, and to Drs. Owyang to receive the very latest, highest- faculty conducted more than 41,000 and Carethers, the University of quality care. The Division’s past, present and future outpatient visits and performed Michigan Medical School congratulates have also been supported by the 184 over 30,000 endoscopies. Research The Division’s success is built upon you on 75 years of success and thanks incredible generosity of many donors. accomplishments continue to gain mo- the foundation laid and sustained you for your commitment to discovery Their gifts have supported professor- mentum, with $15 million in research by visionary leaders: Drs. Pollard, and healing. ships and investigational efforts that funding in 2015. Henley, Nostrant, Yamada and, since enable our faculty to carry out our 1990, Owyang. Along with leading Together, the Division’s scientists and research, clinical care and educational departmental growth, Dr. Owyang has clinicians are advancing discovery missions. further built this vision over the past MARSCHALL S. RUNGE, MD, PhD in the broad area of gastrointestinal dis- 26 years by creating an environment A core part of our mission across the Executive Vice President for Medical eases through major fundamental and to ensure ongoing breakthroughs University of Michigan Medical School Affairs clinical research initiatives. Since 2009, in the diagnosis, management and and Health System has been to train Dean, University of Michigan Medical more than 31,000 patients have partic- treatment of the most challenging and prepare the next generation of School Acknowledgements
I would like to express my sincere gratitude to every person whose hard work and dedication to the Division has made our 75 year journey truly remarkable. Our Division today is fortunate to be enriched not only by our faculty, fellows and investigators, but by over 150 talented staff. Every individual’s contribution is invaluable and very much appreciated. Following the 75 th Anniversary Theresa Nester, Administrative Hilary Robinson, Associate Director, Celebration I received many heartfelt Specialist, Division of Michigan Creative, and the Michigan messages from guests letting me Gastroenterology and Hepatology Creative team including, Martin know how much they enjoyed Soave and Ruth Gretzinger, Lori Hirshman, Associate Director themselves at the events. I would like and also Kim Roth, from Outword of Development, Marie Marsneck, to thank the following individuals Communications Development Assistant, and Jane for their tireless efforts to ensure the Bronson, Development Events Team Sincerely, celebration was an overwhelming success. Bill Burgard, Lecturer II, Stamps School of Art and Design Jeff Holden, MBA, Division Administrator, Division of CHUNG OWYANG, MD, Gastroenterology and Hepatology Chief, Division of Gastroenterology and Hepatology
© 2016 Regents of the University of Michigan Honoring the Past, Shaping the Future. 75 YEARS OF DISCOVERY, INNOVATION AND CARE
Division of Gastroenterology and Hepatology
UNIVERSITY OF MICHIGAN HEALTH SYSTEM