Glioma Research Surges in the Department of Pathology and Cell

Volume ?, Issue ? Holiday Edition 2012-2013

Glioma Research Surges This edition of The Newsletter, the 9th in the series, has a lot to cover. The last Newsletter was dedicated to the 25th anniversary of the modern era and included almost all of the recent his- in the Department of tory of the Department, as well as much that occurred many years ago. For those who did not Pathology and Cell Biology see it, it is on-line. There was no room for our usual features: Annals of Administration, New By Lloyd Greene and Peter Canoll Grants, New Faculty, New Administrators, New Residents, New Graduate Students, Promo- tions, Anniversaries, and all of the good things that help to unify a department of almost 400 There were nearly 14,000 deaths from people. This issue returns to that format and we hope to make up for lost time. We also fea- brain tumors in the US last year and for ture a short article that explains the increasing glioma research in the Department. We salute Grade IV glioblastomas (GBM), there is Carol Mason, President-elect of the Society for Neuroscience. There were two laggards for the currently no effective cure. Over the past Anniversary Newsletter-the Breast and Neuropath Services and because we are forgiving, we few years, the Department of Pathology include them here. We are back to saluting our administrators, including the HR staff and also and Cell Biology has become a vigorous Ellie Johnson our Business Manager. We admire all of the many people who got important center for brain tumor research with stud- grants in this difficult financial time. We have many new clinical faculty members. Finally, as ies that define basic cellular mechanisms of a treat, we include some of the more amusing photos from the 25th Anniversary celebration- transformation and that attempt to discov- with captions. Who knew that this group could rock? er new targets for therapy. We are actively engaged in preclinical testing and in the development of clinical trials.

Jim Goldman has pioneered studies on the heterogeneous population of cycling glial precursor cells that are present throughout an entire lifetime and that are likely to give rise to many low and high grade gliomas. Carol Mason to Be President of The Society for Neuroscience His lab is asking if there is any correlation Columbia Pathology Reports (CPR): between changes in precursor types over When do you take over? age and the age-related risk of developing different types of gliomas. Building off of CM: Well, I have a year as president-elect, this work, Peter Canoll’s lab has used genet- which starts on Oct. 10, so I will be president ically engineered mouse models and target- in 2013. Moses Chao from NYU is the current ed retrovirus delivery to test the tumorigen- President. I’m actually the third Columbia ic potential of glial progenitors that reside in person, after Eric Kandel and Mickey Gold- the adult subcortical white matter, and has berg, to be president. The first woman though! shown that these cells give rise to “proneural” gliomas, which account for the majority CPR: Do you have to lobby the government? of low grade gliomas and secondary GBM. Continued on page 2 The Canoll lab has further identified molecular alterations that occur at early stages of glial progenitor transformation and they are exploring their functional significance and potential as therapeutic targets. In This Issue

Antonio Iavarone and colleagues have Annals of Administration...... 3 been targeting the most aggressive forms Our own Carol Mason is President-elect of 25 Years of Neuropathology...... 4 of GBM, namely those with the “mesen- the Society for Neuroscience. Carol report- Elnora Johnson...... 6 chymal” gene expression signature. They edly was elected with a large majority. Since Reyes Retires...... 6 have recently identified the first example the Society for Neuroscience has 40,000 New Faculty...... 7 of a highly oncogenic gene fusion protein members, this means more people voted for Stephen Francis Ryan, M.D...... 8 On the Shoulders of Giants...... 9 (FGFR-TACC) associated with a subset of her than for Newt Gingrich and Rick Perry Pathology of Crossword Puzzles...... 10-11 GBM and have shown that targeting this combined in the New Hampshire Presiden- 25th Anniversary Party...... 12-13 protein with an oral FGFR inhibitor sig- tial Primary (CPR is from New Hampshire New Grants...... 14 nificantly prolongs survival of mice bear- and knows these things). On this proud Personalized Genomic Medicine...... 15 ing tumors initiated by the fusion protein. note, we interviewed Dr. Mason: Columbia’s Academic Title System...... 16 Continued on page 2 Carol Mason (continued from page 1) Glioma Research Surges in the Department (continued from page 1) CM: Well, believe it or not, the SfN has a building in Washington and a staff of 90 and we already have a lobbying staff, led by Marty Saggese. Recently, the Association for Neuro- sciences Graduate Programs was folded into the SfN, making it even larger. I should say that we are proud that 30% of our members are from other countries. It is clear that neurological problems, particularly with autism at the beginning of life and with dementias later in life cause enormous anguish and drive up medical costs. The SfN has always been in the forefront of studying and find- ing solutions for these problems and I hope to continue that. I am also very concerned about traumatic brain injury.

CPR: The country is waking up, once more, to the importance of science. How do you intend to keep this going?

CM: We need science for the people. We are already doing that, but we need to do more. In March we will have Brain Aware- ness Week and among the things we do is to take human brains into schools and engage students. A model for this is Co- Glial progenitors give rise to proneural glioma. Adult transgenic mice were injected with retrovirus that induces cre-mediated deletion of PTEN and expression of PDGF. At 3 days post injection (3 lumbia University Neuroscience Outreach dpi) there is a small collection of retrovirus infected progenitor cells (green) at the injection site in led by Kelly Remole. With the resources the subcortical white matter (upper panels). By 21 days post-injection (21 dpi) the retrovirus infected of SfN, we can expand this program and progenitor cells have given rise to a tumor (lower panels). Hoechst nuclear stain (blue), olig2 (red). make it better known and more accessible. Courtesy Dr. Peter Canoll. Anna Lasorella, an expert in neural stem that includes all of the above Departmental CPR: But what role do you have in sup- cell differentiation, has closely collabo- members. Among many examples of such porting research? rated with Antonio on such studies. Lloyd collaborative activities is Peter Canoll’s work Greene, in collaboration with ex-post-doc with Jeff Bruce to optimize convection- CM: As I mentioned, the SfN already has Jim Angelastro (now at UC Davis) has fo- enhanced delivery of chemotherapeutics to responsibility for neuroscience graduate cused on ATF5, a transcription factor that the brain and the movement of this work to programs. If we want neuroscientists to is present in neural precursor cells and in clinical trials. Another is the effort between find a way out of the problems that beset various brain tumors and that appears to Antonio Iavarone and Biomedical Infor- all people, we cannot afford blunt force be required by glioblastoma cells, but not matics Professor Andrea Califano to use an trauma to research support. by non-transformed cells, for their sur- integrated computational approach to iden- vival. They have developed and are test- tify both targets and drugs for treatment of CPR: What resources can you deploy? ing cell-permeating peptides that interfere GBM. Additionally, recently appointed chief with ATF5 function and that have been ef- of neuro-oncology, Andrew Lassman, has CM: I am very concerned with ways to fective in eradicating endogenously gener- been advising Lloyd Greene and others in maintain research and careers in this ated gliomas in a preclinical animal model. the Department about translating their po- slower economy. As far as careers are con- tential therapeutics to human trials. We look cerned, I am worried about all stages-from Key to making the Pathology and Cell Biol- forward to the continued progress of brain graduate or medical school, to programs ogy brain tumor effort a first rate program tumor research in the Department and the that allow young scientists to have families. is the highly collaborative and interactive University and to the translation of our ef- I also feel that people late in their careers environment at Columbia both within and forts into new treatments. can make great creative contributions and outside of the Department. Helping to foster are an underused resource. There should this atmosphere is the newly reconstituted be some way to mobilize their talents to Neuro-Oncology program within the Her- the benefit of the next generations of neu- bert Irving Columbia Cancer Center that roscientists. is headed by Neurosurgery’s Jeff Bruce and

2 Annals of Administration: Human Resources

an Associate of Science degree from Solano lives with her son Kevin, who is complet- Community College. Over 30 years in HR ing his junior year at Fordham University- and administration, Paul earned his SPHR Lincoln Center, is proud to be an active (Senior Professional in Human Resources) member in her Parish, and enjoys cooking. certification from the Society for Human Resource Management (SHRM) and the Manual Terrell- Manual joined the Human Resources Association of New PathHR team as HR/Administrative Co- York (HRNY) in 2011. A professional opera ordinator on May 16, 2012. He previously chorister (Tenor), Paul is an active member served approximately 10 years as the lead of the American Guild of Musical Artists HR Representative specializing in full-cy- (AGMA). He hails from Napa Valley, Cali- cle recruitment in the HR Department of fornia, and has been married over 29 years the Western Connecticut Health Network, to Dr. Bruce Smith, retired Dean, School of a non-profit health care network in Con- Liberal Arts, City College of San Francisco. necticut. During his tenure with the West- ern Connecticut Health Network, Manual Abbygale Dove- Prior to joining the also worked for the Housing Department PathHR Team as HR/Administrative Coor- at Western Connecticut State University as dinator in August 2011, Abby served in the a Residential Assistant while obtaining his role of HR Assistant for the U.S. Congres- Bachelor of Arts degree at Western Con- sional Budget Office in Washington, D.C., necticut State University. Manual earned as the Senior HR Assistant for the New York his Master Certificate in Human Resource University ITS Department, and as HR As- Management and a Masters of Business Top-Manual Terrell and Paul Castellano, sistant for the Brooklyn Academy of Music. Administration with a concentration in Bottom, Abbygale Dove and Mary C. Quaratino Abby holds a Bachelor of Arts degree in Human Resource Management. Until the Sociology from New York University and time is right to have his own children, Our PathHR team is now fully staffed. For is currently investigating Masters programs Manual is considering adopting a dog and the past several months, Abby Dove and to enhance her education. While at NYU, enjoying the experience of unconditional Paul Castellano have had the pleasure of Abby also earned a Certificate in Human puppy love...though he admits that a few working with many of you on a myriad Resource Management. Abby’s current pas- goldfish will do for now. Manual hails of HR, payroll, academic affairs, and ad- sions include spending time with her young from the great State of New Jersey. ministrative issues and challenges. We are son Kingston. She enjoys reading, writing, thrilled that Mary Quaratino and Manual fashion, and home decorating projects. The PathHR Team is located in PH 15 Terrell have joined the PathHR Team. Abby hails from Brooklyn, New York. West, Room 1564-G, and can be reached by email at [email protected]. Here is a little background Mary C. Quaratino- Mary joined the edu or by calling (212) 305-7164. We en- on each team member . . . PathHR Team on May 1, 2012, as HR/Ad- courage and welcome you to visit with the ministrative Coordinator. She was recruit- PathHR Team and introduce yourselves... Paul L. Castellano, SPHR – Paul is our ed from within CU (12 years of service) team members will enjoy learning more newly appointed Manager of HR and Aca- where she started as a Temp in Doctors about you, hearing your stories, and solv- demic Affairs. Paul joined the PathHR team Private Offices (DPO) at the uptown cam- ing your HR problems. as Supervisor-HR/Administrative Coordi- pus. She most recently served four years nator in October 2011. Prior to his relocation as Administrative Coordinator with the from San Francisco to New York City, Paul Mailman School of Public Health in the served close to eight years as the Manager of Department of Environment Sciences in Human Resources and Academic Personnel the Columbia Center for Children’s Envi- for the Helen Diller Family Comprehensive ronmental Health (CCCEH), where the fo- Cancer Center at the University of Califor- cus was on environmental factors that af- nia, San Francisco, School of Medicine. His fect Mothers and their Newborns living in previous appointments include Assistant the South Bronx, Upper Manhattan. Mary Executive Director-Council Services for was born, raised, and continues to live in the Girl Scouts of Tres Condados in Santa Washington Heights. Mary graduated Barbara, California, IT Manager for Girl from the College of Mount Saint Vincent Scouts of Washington, D.C., Data Systems with a Bachelor of Arts in Psychology. Af- Manager for the U.S. Air Force Plant 42 in ter college, Mary worked in retail sales and Palmdale, California, and EEO Representa- customer service for many years before tive for Rockwell International. Paul holds joining the Columbia community. Mary

3 25 Years of Neuropathology at Columbia (1987-2012) By Jim Goldman

I arrived at Columbia with Mike Shelanski in and glycobiology. Having been caught in Hospital in 2001 to establish a Brain Bank. 1987 to find a group of experienced neuropa- the Jim Powers web of peroxisomal diseas- Jean Paul has given tremendous time and en- thologists – Phil Duffy, David Cowen, Dick es, Phyllis spent years after her fellowship ergy to develop a modern and first-rate Brain Defendini, and Rusty Hays – in a Division working at Rockefeller to establish the first Bank, which disperses thousands of samples with a long history of work in diagnostic and mouse model of a peroxisomal disorder. each year to laboratories throughout the U.S. experimental neuropathology. The Division She then returned to the fold. Steve Chin and overseas. was one of the first neuropathology divisions (1994) joined us with a strong background in the country, led by Abner Wolf beginning in cytoskeletal biology and an interest in Andy Dwork and Ben Tyko participated in 1930. He was joined by David Cowen in neurodegenerative diseases. After a number in the clinical service for several years and 1937. Together they published seminal pa- of years with us, Steve moved on to the Uni- remain members of the Department. Andy pers on the neuropathology of congenital versity of Utah Medical Center, where he works at the Psychiatric Institute research- toxoplasmosis and other perinatal patholo- became Director of Neuropathology. Kure- ing the neuropathology of psychiatric dis- gies, experimental research on toxoplasmo- nai Tanji (2004) brought to her training in orders, and teaches medical students with sis and viral encephalitis including polio, neuropathology a long experience in mi- us, presenting a grisly lecture on head trau- the effects of X-irradiation on the brain, and tochondrial myopathies acquired with her ma. Ben is a long-standing and prominent the pathology of brain tumors and neurode- husband, Eduardo Bonilla. She has become member of the Cancer Center, investigat- generative disorders. David Cowen, who di- a leading muscle and nerve neuropatholo- ing mechanisms of gene imprinting and rected the Division from 1967-1976, attended gist, first working closely with Rusty Hays gene methylation. Finally, let me say that our teaching conferences beginning in 1987 and then becoming Director of the Nerve we are delighted to have Nadejda Mincheva and we all enjoyed tales stemming from his and Muscle Laboratory. Under her leader- Tsankova, MD, PhD who has joined us long experience. His dry wit and connection ship the Laboratory has continued to grow from UT Southwestern as Assistant Profes- to our past were invaluable. Phil Duffy and and now represents one of the largest and sor of Neuropathology. Dick Defendini directed the program be- most respected nerve and muscle pathology tween 1976 and 1987. One of Phil’s interests centers in the country. Peter Canoll (2002) We have been most fortunate to have had an was astrocytes, about which he wrote a book, joined the faculty with a strong background excellent support staff, includingJoan Hoc- so I have felt at home carrying on the tradi- in glial cell biology. He has developed im- tor, Joan Sullivan, Patricka Jeremie, Chris tion of astrocyte studies. Dick, besides having portant and novel mouse models of glio- deSousa, Linda McCamery, Maddy Kagan, a broad knowledge of neuroanatomy, neurol- mas, now in widespread use, and has been and a dedicated and technically impressive ogy and neuropathology, was a student of the instrumental in strengthening the Pathol- histology staff in our neuropathology labo- history of these disciplines and our guide on ogy arm of the Neuro-Oncology program ratory (when it was a separate lab) nad our many occasions to classic literature and his- at CUMC, including supervising the Brain nerve and muscle laboratory, including Ruby torical perspectives. Rusty was, and still is, a Tumor Bank. Although we are accredited Alcaraz, Maria G. Corotan, Dinnah Neri, renowned expert on nerve and muscle dis- by the ACGME for training 1 fellow each Laarni Gapuz, Rey C. Octavino, Cui Zhen eases, retiring a few years ago as our Director year, in 2008 we applied for a waiver to al- He, Wenhong Li, Evelyn Hernandez-Rosa, of the Nerve and Muscle Laboratory. low us to train 2 neuropathology fellows in and Linda Friedman. that year. They were Andy Teich and John In 1988 the Department hired Jim Powers Crary and because both were excellent, we Through these 25 years, we’ve seen a consoli- as Division Director. Under his guidance we didn’t want to lose either one. Both Andy dation of laboratories, a large increase in the changed our methods of performing frozen and John then joined our faculty in 2010 numbers of specimens and a large increase sections, expanded our immunostaining re- and are currently working on cellular and in the kinds of immuno- and other special sources, and increased efficiency and coop- molecular approaches to Alzheimer disease stains and molecular tests that have become eration with our clinical colleagues. Jim, as and other tauopathies. standards of care in dealing with neuropa- an experienced neuropathologist with high thology specimens. Much of this progress standards and an overabundance of not-so- We have also gone outside our small nest to has been driven by the tremendous advances dry wit, was fun to work with and solidified bring in neuropathologists from far away in our understanding of the complicated our excellent relationships with neurosur- institutions. Yuan Chang (1993) came to us molecular events that regulate the growth of gery and neurology, which have continued. from neuropathology training at Stanford, brain tumors and the development of neuro- When Jim left for Rochester, I took over as and although her diagnostic and teaching degenerative disorders. Columbia has been a Chief of Neuropathology. skills are first-rate, she decided to pursue terrific and fertile place in which to work and in addition a laboratory program looking to grow our Division. We have taken advan- We have been fortunate to have attracted a for viruses in Kaposi’s sarcoma. Together tage of the strong basic science and clinical group of excellent neuropathology fellows, with her husband Pat Moore she discovered neuroscience communities at Columbia for some of whom we have even persuaded HHV-8, now recognized as the causative invaluable collaborations and also for the op- to remain in our Division. Phyllis Faust agent in Kaposi’s. Yuan and Pat moved on portunity to offer our fellows an education in (1996), among our first trainees, came with to Pittsburgh in 2002. Jean-Paul Vonsattel any of a wide variety of neuroscience areas. strong background in lysosomal function moved here from Massachusetts General

4 The Med to Grad Program Honors and Awards

Asa Abeliovich received the coveted 2012 NIH Director’s Transformative Research Projects award.

This is an NIH Program that focuses on very high risk and potentially transformative proposals. As Asa explains it:

We are pursuing improved cell and animal models of human brain disorders, as well as novel cell therapy strategies for brain diseases. Recently, we succeeded in the directed conversion of human patient skin fibroblasts to neurons, achieved by intro- ducing a ‘cocktail’ of pro-neural factors. Such cell reprogramming approaches may allow for the facile generation of replace- ment cells for some brain disorders. We have also applied this technology to model Alzheimer disease pathology, with the in- tention of pursuing disease mechanisms and testing potential therapies. Top row: Kristin Politi (Pathobiology Program, Serge Przedborski’s laboratory); Gannie Tzoneva (Pathobiology Program, Adolfo Ferrando’s laboratory); Maria Avrutsky (Integrated program, Tae-Wan Kim’s laboratory); Kip Kitur (Pharmacology Program, Alice Prince’s laboratory). Bottow row: Kenta Yamamoto (Pathobiology Program, Shan Zha’s laboratory); Deepti Mathur (Integrated Program, Ramon Parson’s laboratory); Shannon Rose (Nutrition Program, Tim Wang’s laboratory); Yuxi Lin (Nutrition Program; Tony Ferrante’s laboratory). Kris Smith, RN Will Vanti Kris Smith has joined Pathology & Will moved to NYC from Toronto in 2003 Cell Biology’s Central Administrative team and took his first job as a lab technician/ as our Practice Manager. manager at Mount Sinai. In 2005 he joined Asa Abeliovich’s lab and has been in Colum- Kris reports to Joann Li and is responsible bia ever since. He will take over some of the for providing leadership in our clinical duties of Carl Reyes. Will says, “I was happy operations. She will partner with our Divi- to be offered a chance to try something dif- This image shows human skin fibroblast cul- sion Managers to coordinate and monitor ferent in this new administrative position, tures that have been converted to brain neurons our clinical services and outreach efforts although I do miss holding a pipette from using a ‘cocktail’ of neurogenic genes. The cells and our billing operations. Kris works time to time. I am glad to have the opportu- were then fixed and stained with antibodies closely with our Faculty leadership and nity to contribute to the research efforts of for a general neuron marker (MAP2, in green) and an Alzheimer’s disease associated protein, ColumbiaDoctors in overseeing all prac- the department in this new role!” Amyloid Precursor Protein (in red). tice-related activities.

Kris served as a Division Administra- tor in Surgery at Columbia, for four years. Prior to that, she worked at South Nassau Communities Hospital. Before taking her current job, Kris consulted for Allscripts on the CROWN implementation here at Website Re-engineered The Pathology and Cell Biology depart- CUMC. Kris’ background is in nursing and mental website has been re-engineered. It in health care administration. Her office is now features drop down menus. If the sec- in PH15W-1564 and she can be reached at tions relevent to your responsibilities need 212-305-3935 or [email protected] revision, please gather all new materials and then contact Ping Feng and Rich Kes- sin who will see to the implementation.

5 Elnora Johnson- Regrettably, Reyes Retires aged the merger of the Anatomy and Pathol- Our business manager ogy Departments and oversaw the alliance with the Motor Neuron Center. Carl closely supervised the Clinical Outreach Program as part of his successful effort to increase the Department’s services and revenues.

Carl became a police officer in 1969, which was considerably better than driving a bread truck in the middle of the night. He retired as a Lieutenant, Commanding Of- ficer, Quartermaster Section in 1990. He become Associate Director of NYC EMS in the Health and Hospitals Corporation. For eight months, before coming to Columbia, he was a member of the Fire Department, completing an unusual tour.

While at the Police Department, Carl was the winner of a special mayoral scholarship After long service to the NYPD, the NYFD under Mayor Koch to the Kennedy School In its continuing efforts to recognize the and the Department of Pathology and Cell of Government. There he earned a Master’s administrators that make the Department Biology, Carl Reyes has decided to call it a of Public Administration and how to row function (no, you academics, it does not day and retire to the more exhausting du- in an 8 man shell and a single person skull. just happen), the Newsletter would like to ties of grandchildren and his wife Marge’s He recalls this as a wonderful year and is recognize our Business Manager, Elnora need to travel. Carl was the Departmental grateful to Mayor Koch to this day. Johnson. Ellie began her employment with Administrator for 15 years. Barnard College back in 1979 and has been Carl has been married to the incredibly ener- at Columbia since 1981. She was recruited During these 15 years the Department’s getic Marge Reyes for 48 years and has three to our Business Office in 2002, later became clinical revenues increased by double dig- children and three grandchildren to whom our Budget and Finance Manager and was its every year. He oversaw the renovations he is devoted. Marge has already scheduled promoted to Business Manager in 2010. El- of 60,000 sq. ft of Pathology space. He gra- trips to Montreal in January (what was she lie comes to us with extensive experience ciously dealt with numerous needy faculty, thinking?) and to Israel in March. Finally, from the downtown campus. As former De- none of whom knew that he still maintains Carl has been the squash partner of Rich partment Administrator for both the Math- his Police Department gun permit. He man- Kessin, who will miss him terribly. ematics and Philosophy departments, Ellie is our go-to resource for accounts payable, system. The new system is named ARC, for Our Far Flung purchasing, capital expenditures, budget Accounting and Reporting at Columbia. El- submissions and financial closes. Since Ms. lie was instrumental in our implementation Photographers Johnson became the Business Manager, the of the new system and has agreed to take on The Master Barista of Santiago Department has greatly improved our busi- the heroic role of ARC liaison for the Depart- ness operations. ment. Our transition to this new system was eased by thorough training and prepared- Ellie has a reputation, on both CU campuses, ness, thanks to Ellie. as a leader, problem solver and facilitator. Her understanding of our complex medical cen- Our next hurdle will be using the new system ter has enabled her to navigate our systems for our budget forecasts for fiscal year 2014! and overcome challenges despite ongoing That process is already underway and will be changes, increased regulations and limited in full swing right after the New Year. Once resources. At times this puts her in the po- again, we can count on Ellie to keep us to task sition of “enforcer” since she’s charged with and to meet all deadlines imposed upon us ensuring pathology processes meet both in- all the while keeping the day-to-day business ternal and external standards. If she or her processing moving along. staff require additional documentation, it’s not to be difficult but because they are trying Ellie also dotes on her family, especially her to protect both you and the department. grandchildren Romona Carter, Zakiyah Cart- er, Sharaya Carter and Shakai Black Johnson. This past year, Columbia took on the tremen- I’ll have the half-caf, double shot non-kosher dous task of implementing a new financial Thank you Ellie! latté please. Mike Shelanski, Chile, August 2012

6 New Faculty

Yvette C. Tanhehco, MD, PhD Patricia Tiscornia-Wasserman, MD Daniela Hoehn, MD Assistant Professor Associate Professor Assistant Professor of Clinical Pathology & Cell Biology Pathology & Cell Biology of Clinical Pathology & Cell Biology (appointed July 2012) (appointed August 2012)

Jorge L. Sepulveda, MD, PhD Abel A. Gonzalez, MD Associate Professor Alina C. Iuga, MD Assistant Professor Pathology & Cell Biology Assistant Professor of Clinical Pathology & Cell Biology of Clinical Pathology & Cell Biology (appointed July 2012) (appointed September 2012)

Antonia R. Sepulveda, MD, PhD Professor of Pathology & Cell Biology

Xiaolin Liu-Jarin, MD, PhD Nadejda Mincheva Tsankova, MD, PhD Richard O. Francis, MD, PhD Assistant Professor of has been a fellow for 2 years, but with us for Assistant Professor Clinical Pathology & Cell Biology 4. She was an AP/NP resident - 2 years AP of Clinical Pathology & Cell Biology (appointed January 2012) residency, 2 years NP fellow. Her photo and (appointed December 2011) story will appear in our next issue.

Our Current First Year Residents

Top row, l-r Jaya Pradhan, DMD, Oral Pathology Diana Sung, MD, Anatomical and Clinical Pathology Najiyah Kazi, MD, Anatomical and Clinical Pathology Amy Coffey, MD, Anatomical and Clinical Pathology Bottom row, l-r Jerry Wang, MD, PhD Anatomical and Neuropathology Jung Hoon Son, MD Anatomical and Clinical Pathology Armando Del Portillo, MD, PhD Anatomical Pathology

7 The Pathobiology Grad students In Memorium

Stephen Francis Ryan, M.D. (“Steve”), of Haworth, New Jersey, died on July 22, 2012 from complications associated with Al- zheimer’s disease. He was 77 years old.

The Department is pleased to welcome (belatedly) the 2012 class of Pathobiology graduate students. The eldest of three children of William and They include, from left to right: Jing Du, Peking University; YoungJoo Yang, Stony Brook University; Martin Jacko, Masaryk University (Prague) and Corentin Moevus from the Université de Montréal. Dolores Ryan, Steve was born in Durango, They have begun rotations and are also taking Biochemistry and our novel Mechanisms of Disease course. Colorado on June 6, 1935.

Faculty Promotions Nadejda M. Tsankova, MD, PhD Steve is survived by his wife Nancy, his Assistant Professor of Pathology & Cell daughters Elaine and Elizabeth Ryan, Ce- lia Baney, and Lynne Andujar, his sons-in- Gilbert Di Paolo, PhD Biology (appointed July 2012) law James Baney and Stephen Andujar, his Associate Professor of Pathology & Cell grandsons Stephen and Michael Baney, his Biology (in the Taub Institute) with tenure Stephen M. Lagana, MD Assistant Professor of Clinical Pathology siblings Thomas Ryan and Diane Savell, and his nieces Kelly Larson and Karen Barbera. Vimla Aggarwal, MBBS & Cell Biology (appointed July 2012) Assistant Professor of Clinical Pathology He was an inspiration to current resident & Cell Biology (appointed July 2012) Marcela A. Salomao, MD Assistant Professor of Clinical Pathology Patricia Raciti. & Cell Biology (appointed July 2012) Steve graduated from Regis College in 1957 and received his M.D. from the University Our Far Flung Photographers Rainbows Over Pathology by Joann Li of Colorado Medical School in 1961 where he was a Boettcher Scholar. He served his internship at the Columbia Division of Bel- levue Hospital in NYC from 1961 to 1962, and his residency in Pathology at the Univer- sity of Colorado Medical Center from 1962 to 1964. He was appointed Fellow in Pathology studying electron microscopy in 1965.

Steve’s distinguished career at St. Luke’s- Roosevelt Hospital Center in New York City spanned from 1966 to 2000 where he became Chief of Anatomic Pathology. He also taught at Columbia University Col- lege of Physicians and Surgeons in New York City from 1966 to 2000 and became Professor of Clinical Pathology. He specialized in pulmonary pathology with over 150 publications in the field 8 On the Shoulders of Giants Hanina Hibshoosh, MD In my office, neatly and classification have withstood, in many This effort is ongoing as a new generation piled and undis- instances, scrutiny even in the molecular of dedicated physicians, scientist and their turbed, I recently era and became a template for us all. associates takes the mantle forward to im- found a collection prove our patients lives…the giants are of bound papers We now gather to celebrate and reflect on a wind in our sails! I can hear the voices I inherited from yet another transformation that has oc- of the future speaking of them now, some the late Dr. Raffa- curred in the past 25 years in the depart- from yellowing pieces of paper, some from ele Lattes upon his ment of pathology. As such we are remind- the cloud, saying thank you, thank you, retirement. These ed that great men and women dedicated to thank you! For those who know not the bound documents a single principle have long served the De- past, rest assured the giants were here. with their yellowing frayed paper, but undi- partment of Pathology. Their goal is to gain minished value, chronicle the minutes of the a better understanding of disease so we can “Arthur Purdy Stout Club” over more than diminish its consequences to future genera- three decades. tions and so that we can live better, more fulfilling lives. We are a part of an unbro- The first of such volumes is a witness to the ken chain dedicated to this goal. The past 25 creation of the “Arthur Purdy Stout Club” years have been thrilling as the department and it reads as follows: under Dr. Shelanski’s guidance, emerged as a focus of discovery, innovation and excel- “MINUTES OF FOUNDER’S MEETING” lence in diverse fields from cancer to neuro- The Arthur Purdy Stout Club biology. The discovery of PTEN, HHV8 role in Kaposi’s sarcoma, BCl6 role in lympho- On July 14, 1947, a small group of scientists, ma and beyond, and the participation in the having in common a deep and absorbing creation of the preeminent neurobiology interest in pathology met in the Vanderbilt center in the world with its two Nobel prize hotel, New York City, with but a single aim winners (Dr Kandel and Dr. Axel) are but - to do honor to their teacher and friend, a few of the transforming events. Equally Dr. Arthur Purdy Stout.” important is the creation of a culture where the adherence to the ideal and dedication to Dr. Arthur Purdy Stout, 1885-1967, founder of These men include: Asa Beach, Vincent P. excellence is primary. American Surgical Pathology Collins, John P. Heaney, Cushman D. Haa- gensen, Robert C. Horn, Raffaelle Lattes, William L. Lehmann and Alvin O. Sever- ance. (It was in the days, now mercifully Scenes We Would Like to See over, before women had a large impact. In this context see the article by Heidi Rot- terdam on Women in Pathology in the last newsletter. It is on our website).

The men, “hereinafter known as the found- ers, had two desires. First, a profound admiration and sincere devotion for Dr. Stout, their teacher, and second, to continue the keen intellectual interest and curiosity in the things he teaches. They felt that both aims could be simultaneously accomplished by organizing and naming for him a club composed of a select group of professional men with an honest interest and respect for pathology as taught by Dr. Stout. It was felt that the greatest amount of admiration could be shown him in this manner.”

Dr. Arthur P. Stout, a surgeon by training, became the father of soft tissue pathology and surgical pathology in the United States. His thoughts, contribution, methodologies Courtesy McKim, Mead & White, later alterations by Lloyd Greene, PhD

9 The Pathology of Crossword Puzzles by Diane Hamle-Bena, MD

A Message from Dr. Marboe This crossword puzzle has been created by Dr. Hamele-Bena. Completing it will acquaint you with the outstanding history of our department, among other things. It is my feeling that all residents should be able to complete this puzzle. Please deliver your completed puzzles, in ink, to Ms. Casey Schadie by February 15. No collaboration, please.

Charles Marboe, MD Residency Program Director

1 2 3 4 5 6 7 8 9 10

12 13 14

15 16

18 19 20 21 22 23 24

25 26

27 28 29 30 31

32 33 34 35 36

38 39 40 41 42

44 45 46 47 48 49

51 52

53 54 55

56 57 58 59 60 61

62 63

64 65 66 67

69 70

71 72 73 74

76 77 78 79

81 82 83 84

86 87

10 Across 69. Red skin eruption or a large number of 26. Same as 43 across 1. Spherical Gram positive bacterium instances in a short time 29. Fishes with lancet-shaped spines causing skin infections 71. Pathologists keep an eye on this on their tails or people who procure tissue 9. Powder formerly used in surgical gloves 73. Granulomatosis with polyangiitis for pathologists 11. Big toe 74. Malady commonly affecting tooth, 31. Posthumous examination head, and heart 12. Tracheal branches 32. Objects on which tissue or cells 13. Taxonomic group containing one or 76. Catecholamine released when one is are placed for microscopic examination more species pulled over by a cop (2 words) 14. Negatively charged ion 78. Makes the dentist’s “stick” less unpleasant 33. Not communicable (of disease) 15. Ribonucleic acid found in nucleus of 80. Portion of medicine taken at one time 35. Purified hydrocarbon wax used for cell, for short or street name for LSD embedding histologic specimens 16. The Heights 81. Form of brain imaging that registers 37. Stain commonly used to treat tissue blood flow to functioning areas sections for microscopic examination 17. Pertaining to the nose 83. “Salesman” for West Nile virus 38. Tubular medical device used to 18. Doctors’ homes-away-from-home 84. Surgical removal of part of a structure withdraw fluids or keep a passage open 22. Agent containing double stranded or organ 39. One who cuts tissue for scientific RNA and implicated in some cases of examination infantile enteritis 85. Unspecialized cell that gives rise to differentiated cells or a small instrument 42. College of American Pathologists 24. All except pulmonary carry used for smoking crack O2-poor blood 45. Home of parathyroid and 86. The act of obtaining CSF or thyroid glands 27. What may result from the chickenpox Astaire’s specialty virus reawakening 47. Biologist who studies the structure 87. Long-haired piano genius of yesteryear and function of cells; 28. Small tissue piece procured for diagnosis Papanicolaou was a famous one 30. Great artery Down 48. Units of electrical resistance or 32. Neural structure On Her Majesty’s Service 2. Mouth infection or excellent singer with 34. Involuntary muscle contraction spotted underparts 49. A pain in the butt sometimes is this 36. Contaminate with a pathogen again 3. Spasmodic inhalation or sound made by 55. Brain and spinal cord, for short 38. Part of a microscope that concentrates inebriated cartoon character 57. Abnormally small production of urine light on a subject or a device used to change 4. Area between thorax and pelvis or cloth 58. Aggregate of cells having similar vapor into liquid sported by Johnny Weissmuller structure and function or a necessity for 40. Act performed on tissue to facilitate 5. Fully differentiated structural and a tear jerker rapid diagnosis functional units specialized for particular 61. Investigative functions of 26 down functions or life-enhancing instruments 41. Did Popeye exercise these? 62. Antonie, the father of microbiology seldom found in operating rooms 43. Agency that helps make 16 across safe 63. Dr. Lefkowitch would never consider 6. Fleshy, wiggling lobe in the mouth of a eating this for dinner 44. Unsaturated hydrocarbon, e.g., ethylene screaming cartoon character or unpopular 46. Veterinary version of 31 Down party favor given by cannibals 65. To move the teeth into their proper positions or to join with others in a cause 50. Some employees at Columbia are 7. Tool used to flatten bones during surgery 66. Empty or acalculous gallbladder fortunate to see this run by their windows 8. Type of wound often found in 51. Rudolf, the father of modern pathology gunshot victims 68. Subjective evidence of disease 53. Gastrointestinal stromal tumor or the 9. Opposite of longitudinal 69. Treatments that relieve or cure disease core essence of something 10. Propagating genetically identical 70. Making a crossword puzzle is 54. Gonorrhea (slang) organisms than I thought 56. Person who asks you to hop on one foot 11. The study of tissues 72. Chronic noninfectious granulomatous disease and touch your nose 19. Eosin is one 75. Protein found in microfilaments and 59. Of great interest to both jail wardens 20. Hormone regulating the storage of active in cell movement or the other thing and pathologists glycogen in the liver Dolly Parton’s good at besides singin’ 60. Inflammation of the large intestine 21. NH2 or a type of acid necessary for 77. Having a sudden onset, sharp rise, 64. Department of Pathology and protein synthesis and short course Cell Biology’s top dawg 22. Curved arch of bone or a teasing remark 79. Tube carrying the secretion of a gland 67. Baby Drosophila 23. Electronic device that generates a digital 81. Adipose tissue or Nanna Jenny 68. The state of having descended from a representation of an image 82. To tear or split apart or common common ancestor 25. Ailments tombstone inscription

11 Photos From the 25th Anniversary Party Charles Manley was the photographer for our 25th Anniversary Party. He has created a website called “2175 Pathology 25 Years” to share pictures with friends and family.He would like you to be a member of the site. Check it out at http://pathology25years.shutterfly.com/. Find hundreds of pictures, of which the ones shown below are not necessarily the only good ones. PASSWORD: pathologycumc

The Clinical Pathology guys, Eldad Hod, Mahesh Mansukhani Richard Francis and Steven Spitalnik

Waddya mean I can’t dance? Joann and Eugene Li

Master of Ceremonies Lloyd Greene

Mike and Vivien

Karen Duff. In the moment. Ron Liem and Julie Canman Dr. Joseph Point du Jour, Dr. Kimberly Point du Jour and Kim’s mentor Gil Di Paulo

12 The Yes-I’m-Tenured-Tango. Gil Di Paulo and Rich Kessin They had a lot to drink.

“I am the captain of Pathology “Yeah, well I was the captain of the and I command a right good crew!” USS Harry S. Truman and my crew was pretty Chairman Mike Shelanski good too. Do your guys make carrier landings?” Rear Admiral Herman Shelanski

Salomé and Chris Henderson

Carl and Marge Reyes Michael Shelanski

Chuck Marboe and Vivette D’Agati Carol Mason, Gregg Gundersen and Fiona Doetsch Patrice and Steve Spitalnik

13 New Grants

Our Faculty have continued to compete successfully for research support. In addition to Kim, Tae-Wan the grants listed below, The Newsletter would like to note that this year we have successful- Novel CNS Transporter Target in ly renewed the training grants for the MD/PhD program and for the CMBS graduate pro- Alzheimer’s Disease gram. The first was under the direction of Dr. Michael Shelanski who would like to thank American Health Assistance Foundation Patrice Spitalnik and Jeffrey Brandt for their hard work in assembling our application. The critical Cellular, Molecular and Biomedical Training Grant application was organized by Laufer, Edward Ron Liem who would like to thank Zaia Sivo and Fred Loweff. We also note the renewal of Molecular Regulation of Adrenal Cortex the Vision Training Grant by Carol Mason, who thanks Josie Salcedo for her help. Homeostasis and Remodeling, (RO1, NIDDK, NIH) Abeliovich, Asa Doetsch, Fiona 1. Human Induced Neuronal Stem Cell 1. Angel Maldonado-Soto: Identification Mao, Yinghui Models of Familial Alzheimer’s Disease-NIA and Regulation of Quiescent Stem Cells in Formin mDia Functions in Mitosis (see page 5) the Adult Brain (F31, NS,NIH) (RO1, NIGMS)

2. Characterization of human-induced 2. Perivascular niche for adult neural stem Mason, Carol Ann neuronal (hiN) cells from Alzheimer’s cells (R21, NS, NIH) 1. Growth and Guidance of Retinal Axons disease (AD) patients’ skin (Merck) (RO1, National Eye Institute) Faust, Phyllis Awano, Tomoyuki/Monani lab 1. Essential Tremor: Gene Expression 2. The Role of Zic Genes in Patterning Investigating the existence and role of Profiling in Cerebellar Purkinje Cells the Binocular Projection (RO1, National genetic modifiers of SMA modifiers in (R21, NS, NIH) Eye Institute) model mice (MDA) Gershon, Michael 3. Vision Sciences Training Grant Clark, Lorraine Microenvironment in Enteric Neuron (T32, NIH) Parkinson’s Disease Foundation (PDF) Development (RO1, NS, NIH) 30th year! Research Center Grant 2012-2013 (PDF) 4. Genes that regulate retinal ganglion cell Goldman, James identity, Fight for Sight, Inc. Clynes, Raphael Alexander Disease: Cellular and 1. Columbia University Medical Center Molecular Mechanisms (NIH, with McCabe, Brian Skin Disease Research Center (CUMCS- University of Wisconsin) Disruption of neuronal NF-kB signaling DRC), National Institute of Arthritis and by TDP-43 and FUS/TLS mutations in fa- Musculoskeletal and Skin Diseases Greene, Lloyd milial ALS, Amyotrophic Lateral Sclerosis 1. Neuron Death in Parkinson’s Disease: Association 2. Enhancing the Vaccinal Effect of Anti- The Role of Trib3 (RO1, NS, NIH) tumor Antibodies (NCI) Mentis, George 2. Parkinson’s Disease Foundation (PDF) Mechanisms of Central Synaptic Crary, John Research Center Grant 2012-2013 Dysfunction in SMA, (RO1, National Role of microRNAs in tangle predominant Institute of Neurological Disorders Alzheimer’s disease 3. Defeating insect-borne diseases using and Stroke/NIH) American Health Assistance Foundation atomic resolution structure, Bumpus (William N and Bernice E) Foundation Monani, Umrao D’Agati, Vivette Denise 1. Novel Genetic Determinants of the Aging & Vulnerability to Ischemia: 4. Mechanisms of Dopamine Neuron Neuromuscular SMA Phenotype Pathways & Rescue (with NYU), NIH Degeneration (P50, NS, NIH) (RO1, National Institute of Neurological Disorders and Stroke/NIH) Di Paolo, Gilbert Gundersen, Gregg 1. Role of Phosphoinositides in Neuronal Role of Nucleo-cytoskeleton Interactions 2. Mouse model of Aromatic Membrane Traffic and Neurodegeneration, in Cell Migration (RO1, NIGMS, NIH) L–amino acid decarboxylase deficiency, (RO1, NS, NIH) (AADC Research Trust, ALADD Henderson, Christopher Foundation, and the Pediatric 2. Kimberly Robinson: The Study of Contribution of neurotensin to degenera- Neurotransmitter Disease Association) Phosphatidic Acid and Phosopolipase D tion of vulnerable motor neurons in ALS. in membrane trafficking, (F31, NIH) Amyotrophic Lateral Sclerosis Association 3. Identifying spinal muscular atrophy modifiers (SMA, Europe)

14 New Grants New High Throughput Sequencing Capacity for Personalized Genomic Medicine Pellizzoni, Livio 1. Role of Stasimon Dysfunction in Spinal Muscular Atrophy. (R21, National Institute of Neurological Disorders and Stroke/NIH)

2. Sarah Tisdsale: Molecular and cellular characterization of SMN-mediated U7 snRNP assembly, (F31, National Institute of Neurological Disorders and Stroke/NIH)

Przedborski, Serge 1. Localization of a-synuclein in mitochondrial-associated ER membranes. (Parkinson’s Disease Foundation)

2. Parkinson’s Disease Foundation (PDF) Research Center Grant 2012-2013

3. Mechanisms of Dopamine Neuron Degeneration (P50, National Institute of Dr. Peter Nagy and his team blocking the view of their HiSeq 2000. Neurological Disorders and Stroke/NIH) They are: (l-r) Jane Dunning Broadbent, Nicholas Rouse and Melissa Pang, not shown are Samantha Pottinger and Stuart Andrews 4. Cell-based assays for the screening of In October we celebrated the arrival of a Our Far Flung neuroprotective small molecules for ALS, new member of our Next-Gen sequencing (Amyotrophic Lateral Sclerosis Association) family; a HiSeq 2000 machine. with the Photographers capacity of 800Gb output per run. That is Tired of Academia? Try this! Spitalnik, Steven equivalent to a full diploid human genome 1. Harmful effects of transfusion of older with a 100-fold coverage. What was a ten- stored red cells: iron and inflammation, year project a decade ago, can now be ac- (RO1, National Heart, Lung, and Blood complished in two weeks. With this, the era Institute/NIH) of clinical full-exome and full-genome sequencing has officially started at Columbia. 2. Mechanisms of Effect of Iron Status & Interventions on Malaria & Other This new instrument joined the Illumina Infections, (National Institute of Child GAIIx and the MiSeq machines already Health and Human Development/NIH) in clinical operation for mitochondrial genome sequencing. The new machine will Wichterle, Hynek be used for full-exome sequencing of pa- 1. The Role of mir-17~92 Cluster in Motor tients with genetic conditions in the care Neuron Degeneration, (R21, National of our colleagues in Pediatrics, Neurology, Institute of Neurological Disorders and and several other departments. It will be Stroke/NIH) the workhorse of our clinical operation, as well as a program project grant submitted 2. Motor neuron selector genes and jointly to the National Human Genome mechanism of their action, (RO1, Research Institute by PGM at CUMC, the National Institute of Neurological Cold Spring Harbor Laboratories and the Disorders and Stroke) New York Genome Center. The goal of this grant application is to establish the techni- For our national ranking in NIH funding, cal and ethical framework for the use of A photo taken by our creative director see the last page. Next-Gen sequencing in the clinical arena. Richard Miller while on vacation in The results it will provide will shorten the Jamaica. The rainbow and the jumper diagnostic odyssey of our patients and pro- were real. The Caribbean was 120 feet vide a wealth of new information about the below. The diver lived. molecular causes of human disease and human genetic diversity.

15 The Art of Cell Biology Departmental NIH Funding Dean Goldman has informed us that our Department ranks fifth among Pathology Departments in the country in NIH funding, at nearly $28 million. Emory is number 1 with nearly $32 million, followed by The University of Pennsylvania and the University of Washington. Johns Hopkins is also ahead of us. We’re way ahead of whoever is 6th (NYU).

Our Diagnostic Services

The Department offers a very broad range of expertise and diagnostic services. We are available for consultation at the follow- ing locations.

Web: www.pathology.columbia.edu Email: [email protected] An inadvertant double helix. Beautiful, but serious, this is a solid pseudopapillary tumor of the Laboratory services: pancreas. Courtesy of Anjali Saqi, MD, MBA 1-800-653-8200/1-212-305-4840 Administrative Services: A Guide for the Perplexed: 1-212-305-7164 Columbia’s New Academic Title System It is well known that the three most complicated things in the world are: Medical Billing, Columbia’s system of academic titles, and The General Theory of Relativity. In that order. A Note on Publications Now, fulfilling a mandate from Dean Goldman, Dr. Anne Taylor, has led a committee to reform the title structure. The title structure system has been simplified and changed The members of the department contributed to recognize all types of contribution to our Medical Center. The areas of focus include: approximately 260 peer reviewed publica- Research, but also Education and Clinical and Public Health Practice. These changes will tions in the years 2011-2012. The newsletter be introduced next summer. To learn about them visit: http://www.cumc.columbia.edu/ suggests that interested parties search the faculty/. Log in and click on Restructure of the Academic Tracks. This should help. Dr. websites of the individual faculty members Taylor informs us that more information will be forthcoming. at http://pathology.columbia.edu/

Volume ?, Issue ? Holiday Edition 2012-2013

Chairman http://pathology.columbia.edu/ The Columbia Pathology and Dr. Michael L. Shelanski Cell Biology Report is a publication Delafield Professor of Pathology Senior Associate Proofreader of the Department of Pathology Pathology and Cell Biology Ms. Casey Schadie and Cell Biology at the Columbia Editor Coordinator of Residency Programs Dr. Richard H. Kessin Department of Pathology and Cell Biology University Medical Center. Professor If you have comments or Pathology and Cell Biology questions, contact: Design and production Dr. Richard H. Kessin Richard V. Miller at 212.305.5653 CUMC IT Email: [email protected]