Summer/Fall 2013

Center for Clinical and Translational Science

e-Newsletter

Center News Dr. Christopher Austin, New Director of the National Center for Advancing Translational Sciences (NCATS), Visits Rockefeller By Barry Coller not have extensive experience in human subjects research. Ed Barbour described the comprehensive, self-guiding, electronic system (iRIS) used for protocol development, protocol review by the Advisory Committee on Clinical and Translational Science (ACCTS) and the Institutional Review Board (IRB), and protocol conduct. The iRIS program underwent extensive customization by Rockefeller CCTS senior staff to incorporate important information in protocol development and conduct and links to source documents.

Dr. Christopher Austin Educational Programs Dr. Elaine Collier

Dr. Christopher Austin, the Director Dr. Florian Klein and Dr. Manish Ponda cell malignancies, to the role of microRNAs of the National Center for Advancing discussed their experiences in the in a variety of diseases, to genetic defects Translational Science (NCATS), and Dr. CCTS Clinical Scholars Master’s degree in human odorant receptors and the Elaine Collier, Deputy Director of NCATS, program and the Rockefeller Early Phase preference of mosquitos to feed on some visited the Rockefeller University Center Physician Scientist (REPPS) program, humans. for Clinical and Translational Science respectively. Dr. Klein has conducted pioneering studies on the efficacy of Dr. Robert Darnell discussed Rockefeller (CCTS) on March 22, 2013 to learn more University’s participation in the New York about the programs supported by the broadly neutralizing anti-HIV antibodies in reducing viral replication in a murine Genome Center (NYGC) and his role as University’s Clinical and Translational President of the NYGC. NYGC provides Science Award (CTSA). The day was model of HIV in Dr. Michel Nussenzweig’s laboratory, and those studies have advanced next generation sequencing divided into discussions of a number of and bioinformatics to all participating different topics. laid the groundwork for future human studies. Dr. Ponda has studied the impact institutes at competitive fees and History of Clinical Research at Rockefeller of vitamin D deficiency and repletion on high quality. This is a vital resource for and CCTS Infrastructure plasma lipids in Dr. Jan Breslow’s lab. Rockefeller scientists. Dr. Ponda’s studies call into question Drs. Barry Coller and James Krueger, PI Bringing Science to the Clinical Research the widespread practice of treating and Co-PI of the CTSA, provided Drs. Enterprise patients with low vitamin D levels with Austin and Collier with an introduction oral vitamin D supplement to improve to the history and unique features of the Dr. Barbara O’Sullivan described her novel their lipid profile and offer insights into Rockefeller University CCTS and Hospital role as a Research Hospitalist providing the mechanism of vitamin D’s effects. and the many important translational support to investigators, especially those without a medical background, and discoveries made in the Hospital. Donna Outreach to Basic Investigators and New insuring patient safety through hospital Brassil gave an overview of the CCTS York Science Collaboration Navigation program, a multidisciplinary policies and procedures. Nina Papavasiliou, PhD, Tom Tuschl, PhD, effort designed to assist investigators Dr. Rhonda Kost described the centralized and Andreas Keller, MD and Leslie Bellani, in developing their human subjects research participant recruitment program PhD from the laboratory of Leslie Vosshall, protocols. The program has reduced she has developed to assist investigators PhD, discussed their human subjects the time to protocol approval while in completing their studies rapidly. research projects in the CCTS from the simultaneously insuring the quality of the By centralizing and standardizing the standpoint of basic investigators. Their protocols. It has been especially valuable process, investigators can assess the research spans from studies of immune for trainees and basic scientists who do progress of the recruitment process and, 1 continued on page 5 Michelle Lowes, MD, PhD Promoted to Associate Professor of Clinical Investigation By Michelle Romanick Dr. Michelle Lowes was recently of inflammatory dermal myeloid dendritic promoted to Associate Professor of cells, which are as abundant as T cells in Clinical Investigation in the Laboratory for psoriasis skin lesions. She is the recipient Investigative Dermatology. Dr. Lowes is a of an NIH independent investigator RO1 graduate of the Clinical Scholars Program, grant entitled, “Origin and Function of and is a current member of the Rockefeller Inflammatory Dendritic Cells in Psoriasis.” University Early Phase Physician-Scientist Her research focuses on identifying (REPPS) group. She obtained her medical the precursors of these inflammatory degree, PhD and dermatology training dendritic cells. These precursor cells offer in Australia. Dr. Lowes has been an NIH- an attractive therapeutic target since funded investigator since 2006, and has inhibiting entry of dendritic cells into also received funding from The Doris the skin could prevent inflammatory Duke Foundation, The Dana Foundation, skin lesion development, as well as treat the National Psoriasis Foundation, and existing lesions. Her experiments will the Rockefeller University Clinical and enhance our knowledge of monocyte Translational Science Awards (CTSA). populations and the dendritic cells and macrophages they give rise to, and Michelle Lowes MD, PhD Dr. Lowes is studying the chronic provide insights into the development of inflammatory skin disease psoriasis, new treatment protocols that target these mainly from a “dendritic cell-centric” point cells in psoriasis and potentially other of view. The lab first described a population autoimmune diseases.

Dr. Edgar Charles, Clinical Scholar Graduate, Joins Merck Research Laboratory By Michelle Romanick

Dr. Charles’s research interest was largely When I joined, the program was one of only driven by his clinical experiences during several in the country that offered clinicians internal medicine residency and infectious a significant amount of protected time in diseases fellowship at NYU/Bellevue. He had the lab. During fellowship, I worked on HIV the opportunity to care for patients with immunopathogenesis in Fred Valentine’s hepatitis C virus infection, many of whom lab at NYU. I knew that I wanted to continue had serious complications from their disease, at the bench after fellowship, and when I with no prospect of effective treatments in heard about Rockefeller’s Clinical Scholars’ sight. He conducted translational research on Program, I was intrigued. I had been the immunopathogenesis of HCV infection, following the work of Charles Rice and with a view to improving the lives of those Lynn Dustin, and given my clinical interests, suffering from chronic viral infections. it was a great fit for me to join their labs. Edgar Charles, MD, PhD Dr. Charles joined the Merck Research Dr. Edgar Charles came to Rockefeller in Laboratories in the winter of 2012 as Director, In addition to providing me with an 2004 as a Clinical Scholar in the laboratories Clinical Research, Infectious Diseases, intensive laboratory experience and access of Charles Rice, Ph.D. and Lynn B. Dustin, Emerging Markets. In this role, Dr. Charles to the Hospital’s extraordinary clinical Ph.D. His studies focused on patients who designs and executes clinical trials of novel research facilities, the programs provided are infected with hepatitis C virus (HCV) and therapeutics for the treatment of infectious an exciting milieu of dedicated translational who subsequently developed autoimmune diseases. Additionally, he authors the clinical researchers. Through this group of peers disease. Dr. Charles received his B.A. from sections of regulatory filings, supports and mentors, I learned how to conduct the University of Chicago and his M.D. from document filing activities and interactions rigorous translational research. The the University of Alabama. He completed with regulatory agencies, and evaluates didactic program formally introduced me his residency in Internal Medicine and scientific and business development to many topics pertaining to commercial fellowship in Infectious Diseases at New opportunities in emerging markets with the drug development; this training has been York University School of Medicine. goal of improving human health through very relevant to my activities at Merck.” Dr. Charles then joined the Rockefeller the development of better medicines. University Clinical Scholars Program and When asked how the Clinical Scholars earned a Master’s degree in Clinical and and REPPS programs prepared him for his Translational Science. Thereafter, Dr. Charles current position, Dr. Charles commented, helped launched the Rockefeller Early Phase Physician Scientist (REPPS) program, “The Clinical Scholars program and REPPS designed to help junior investigators program provided me with an unparalleled achieve scientific independence. opportunity to train as a physician-scientist.

2 New Clinical Scholars Join the Center for Clinical and Translational Science By Michelle Romanick

Five new Clinical Scholars joined the Rockefeller University Clinical Scholars Program on July 1, 2013: Drs. Jose Aleman, Avi Levin, Lotta von Boehmer, Taia Wang, and Ethan Weinberg. Additionally, with support from the Center for Clinical and Translational Science, three medical students joined the Year-Off Training Program for Medical Students in Clinical and Translational Science: Thomas Heineman, Jessica Posada, and Mariya Rozenblit. Below are brief biographies and research interests of the new Scholars and medical students. Please join us in welcoming them.

Jose Alemán, MD,PhD [email protected] Mentor: Drs. Jan Breslow and Peter Holt

Dr. Jose Alemán received his MD and PhD from Harvard Medical School. During his PhD in Medical Engineering at the Massachusetts Institute of Technology, he developed metabolomic and flux analysis techniques to elucidate insulin-resistant metabolism in transgenic mice in collaboration with investigators at the Joslin Diabetes Center. He completed his Internal Medicine Residency and Endocrinology Fellowship at Weill Cornell Medical Center. During the current year, Dr. Alemán has been studying obesity-associated inflammation and its chronic disease consequences in Type 2 diabetes, cardiovascular disease, and cancer in Dr. Jan Breslow’s lab. Dr. Alemán will continue his studies as a Clinical Scholar, including a weight loss intervention study to assess reversal of obesity-associated inflammation, and deployment of noninvasive spectroscopic detection of adipose-tissue inflammation.

Avi Levin, MD [email protected] Mentor: Dr. Hermann Steller

Dr. Avi Levin received his MD from The Hebrew University Hadassah Medical School, Israel, and he completed his Internal Medicine Residency and Gastroenterology Fellowship at Hadassah Medical Center. As a Clinical Scholar in Dr. Steller’s lab, Dr. Levin will be studying the role of apoptosis in the development of colon cancer, bowel wall injury healing, and the compensatory response to massive intestinal resection resulting in short bowel syndrome.

Lotta von Boehmer, MD [email protected] Mentors: Dr. Michel Nussenzweig

Dr. Lotta von Boehmer received her MD from the University of Zurich, Switzerland, and completed her Internal Medicine and Medical Oncology Fellowships at the University Hospital in Zurich. As a Clinical Scholar in Dr. Nussenzweig’s lab, Dr. von Boehmer will analyze the function and development of B lymphocytes in cancer and HIV positive patients.

Taia Wang, MD, PhD [email protected] Mentors: Drs. Jeffrey Ravetch and Sarah Schlesinger

Dr. Taia Wang received her MD and PhD from the Mount Sinai School of Medicine. During her PhD in the Department of Microbiology, she studied innate and adaptive mechanisms of broad-spectrum protection against influenza viruses. As a Clinical Scholar in Dr. Ravetch’s lab, Dr. Wang will be studying factors regulating the composition of IgG Fc glycans in humans and the role that Fc glycans may play in the evolution of humoral immune responses.

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3 New Clinical Scholars Join the Center for Clinical and Translational Science (CCTS) continued from page 3

Ethan Weinberg, MD [email protected] Mentor: Dr. Sohail Tavazoie

Dr. Ethan Weinberg received his MD from the University of Maryland School of Medicine and then completed his Internal Medicine residency and Gastroenterology Fellowship at New York Presbyterian Hospital. As a Clinical Scholar in Dr. Tavazoie’s lab, Dr. Weinberg will be characterizing colorectal cancer metastasis using a xenograft mouse model in which tumors surgically resected from patients are engrafted into immunodeficient mice. He will also focus on the development of agents to target microRNAs that affect signal transduction in metastatic colorectal cancer.

Year-Off Training Program for Medical Students

Thomas Heineman [email protected] Mentor: Dr. Agata Smogorzewska

Mr. Thomas Heineman is currently a third year medical student at Weill Cornell Medical College. His research project will be to study DNA damage responses in human embryonic stem cells (hESc) with abnormalities in the Fanconi anemia pathway., as well as the creation and study of skin equivalents derived from these human embryonic stem cells.

Jessica Posada [email protected] Mentor: Dr. Sohail Tavazoie

Ms. Jessica Posada is currently a fourth year medical student at the University of Colorado, Denver. Ms. Posada’s research project will focus on cancer progression in malignant melanoma, investigating the mechanism by which ApoE mediates its robust suppressive effects on angiogenesis.

Mariya Rozenblit [email protected] Mentor: Dr. James Krueger

Ms. Mariya Rozenblit is currently a third year medical student at the Mount Sinai School of Medicine. She will study the pathogenesis of atopic dermatitis and the effects of cyclosporin A treatment on barrier defects in patients with atopic dermatitis.

4 Dr. Christopher Austin, New Director of the National Center for Advancing Translational Sciences (NCATS), Visits Rockefeller continued from Page 1 if necessary, modify the advertising or the studies, and PatentLens about patents. advanced cabling to support EEG and protocol in response to the data obtained. Dr. Knut Wittkowski provided information visual monitoring. The study was many Lynda Olender, RN, ANP provided about the non-parametric statistical years in development. Several patients information on the mission of the methods he has developed (μSTAT) have already been evaluated and their Helibrunn Center for Research Nursing to facilitate the analysis of clinical and EEG data are providing new insights, with and the programs it has initiated to translational studies, and in particular its some patients’ EEGs showing evidence of advance Research Nursing as a specialty application to genome-wide association receiving auditory stimuli and responding practice. Supported by a $5 million studies (GWAS). appropriately to a motor command even without external evidence of a response. endowment, the Center is creating The latter application allows for more educational programs and a novel refined analysis based on a smaller Enabling Therapeutic Development fellowship program. number of participants. Dr. Fraser Glickman described the new Building Tools for Investigators Worldwide Dr. Kost also described the Research Rockefeller Therapeutic Discovery and 2 Shamim Mollah reviewed the progress Participant Perception project she has led, Development Interest Group (TD IG), of the Center’s human phenotyping including the development of a validated which brings together investigators with initiative for bleeding disorders, a survey to assess participants’ perceptions an interest in therapeutic development, collaboration among Ed Barbour, of their research experience, the fielding as well as the high throughput screening Shamim Mollah, Barry Coller and a past of the survey at 15 NIH-supported clinical facility that he leads. research centers, and the analysis of Clinical Scholar, Andreas Mauer. The Dr. Mina Pastagia recounted her more than 4,900 completed surveys. This project includes the development of experience in developing a phage lytic study is the most extensive sampling of an ontology of all bleeding symptoms, enzyme isolated by Dr. Vincent Fischetti research participants’ perceptions and the creation of a questionnaire with that lyses Staphylococci as a topical provides vital outcomes data for assessing electronic data entry, the standardization therapeutic agent during her training as the effectiveness of informed consent of the medical language employed, and a Clinical Scholar. Since graduating she procedures and the conduct of clinical the ready availability of the instrument has continued her work on developing investigation. via the internet to all investigators. The phage lytic enzyme treatment for other Rockefeller CCTS group also participated Community Engagement and Community indications. in the creation of the International Society Collaborations Dr. Barry Coller concluded the day by on Thrombosis and Haemostasis (ISTH) describing a new joint initiative by Bleeding Assessment Tool (BAT). Based on Dr. Rhonda Kost and Nancy Jenkes Rockefeller University, Memorial Sloan- the success of the Rockefeller initiative, the described the CCTS Community Engaged Kettering Cancer Center, and Weill ISTH invited Rockefeller to host the ISTH- Research program that is co-led by Dr. Cornell Medical College to develop a BAT and Rockefeller has taken on that Jonathan Tobin and Dr. Kost. They provided tri-institutional therapeutic discovery responsibility. A number of investigators details on the Community-Acquired and development initiative (Tri-I TDI). around the world are already using the Methicillin Resistant Staphylococcal The program will provide the resources system, including ones in Italy, Canada, Aureus (CA-MRSA) project, which includes for promising projects to traverse the and the U.K. Ed Barbour described a six federally qualified community health proverbial “Valley of Death,” including parallel effort to enhance the electronic centers, Clinical Directors Network (CDN), medicinal chemistry, toxicology, infrastructure of the International Fanconi which is led by Dr. Tobin, and Dr. Alex formulation, and regulatory support. Anemia Registry to support advanced Tomasz’s laboratory at Rockefeller. This The institutions are also considering genotype-phenotype relationships. bidirectional project combines state of the art clinical care with advanced microbial partnering with a pharmaceutical Michelle Romanick provided information DNA analysis to track the epidemiology of company to help provide some of these on the electronic survey and database this serious infection in the community, resources. developed by the Rockefeller CCTS providing important new information At the end of the day, Dr. Austin and that is designed to track the career that may allow improved interventions to Dr. Collier expressed their appreciation development of graduates from the CCTS prevent recurrent disease. for the amount of information they training programs (GTSS). The survey received about CTSA-supported scientific was specifically designed so that it could Dr. Peter Forgacs, a Clinical Scholar co- discovery at Rockefeller. be adopted easily by other CTSAs and mentored by Drs. Nicholas Schiff of Weill 11 other CTSAs have already done so. Cornell Medical College and Don Pfaff of To facilitate survey completion and data Rockefeller, explained his project to assess aggregation, each graduate’s survey is patients in the minimally conscious state prepopulated with data from PubMed in a specially designed suite of rooms in about publications, Exporter about the Rockefeller University Hospital with grants, ClinicalTrials.gov about clinical

5 Study of Recovery of Consciousness at Rockefeller University Hospital Involves Collaboration with Weill Cornell Scientists By Nicholas Schiff and Peter Forgacs

Severe brain injuries may produce coma, but typically patients have spontaneously Hospital, Weill Cornell Medical Center and a state of unarousable unresponsiveness. regained consciousness. Understanding his Clinical Neurophysiology/Epilepsy While many patients recover from coma the underlying biological mechanisms of Fellowship at Brigham and Women’s quickly, others may remain indefinitely in this recovery process in the severely injured Hospital, Harvard Medical School. Subjects different states that are collectively known brain and developing novel methods for are studied in a dedicated room located in as “disorders of consciousness’. These detection of possible preserved elements the inpatient floor of the Hospital over 2 – 4 syndromes include the vegetative state, of consciousness has been the focus of Dr. days. During the hospital stay, the subject’s which is a condition distinguished from Nicholas Schiff, the Jerold B. Katz Professor spontaneous behavior and brain activity coma by intermittent eye opening despite of Neurology and Neuroscience at Weill is continuously recorded using video-EEG total unresponsiveness, the minimally Cornell Medical College and his team. equipment. Real-time remote observation conscious state, which is characterized by Dr. Schiff, Director of the Laboratory of of the subject is also possible from a separate intermittent and inconsistent responses Cognitive Neuromodulation at Weill Cornell reviewing room on the same hospital to external stimuli, and the confusional is a physician scientist with broad interests floor. A range of behavioral paradigms state, in which patients develop in the area of neurological disorders of are employed to assess the subject’s communication systems but remain consciousness. His research bridges basic language comprehension, response to limited in their capacity to organize and neuroscience and clinical investigative non-linguistic stimuli (such as humor or sustain consistent communication. studies of the pathophysiology of impaired music), and their ability to follow auditory consciousness, the neurophysiological commands or communicate using spoken There are currently an estimated 250,000 mechanisms of arousal regulation, and the language, gesture or novel measurement to 300,000 people in the U.S. who are in a effects of deep brain electrical stimulation tools that can detect mental imagery. minimally conscious state. These patients techniques on forebrain integration. typically live in long-term care facilities or The study at the Rockefeller University in their homes with full-time caregivers. Up Dr. Schiff leads the study of patients Hospital affords the study an optimal quiet until the last decade, patients with severe recovering from disorders of consciousness setting for study procedures and includes a injuries to the central nervous system were at The Rockefeller University Hospital. In multidisciplinary team effort to support the uniformly thought to have no chance for preparation for the study, patient rooms in care of these subjects. meaningful recovery if impaired conscious The Rockefeller University Hospital were Collaborative studies at Rockefeller and persisted for more than 6 months or 1 year, extensively reconfigured to support the Cornell are aimed at improving diagnostic depending on the etiology. However, more monitoring equipment and a dedicated staff assessments and better understanding of recently, several landmark observational observation room was created. Patients recovery mechanisms of consciousness in studies have demonstrated that some started to be studied in the second half of people with severe brain injury. The goal patients may recover over prolonged 2012. The Clinical Scholar working with Dr. is enhance opportunities for people with periods of time following their brain injuries. Schiff is Dr. Peter Forgacs who completed his severe brain injuries to regain their mental Late recoveries have in some instances been Internal Medicine Internship and Neurology functions and thus improve the quality of linked to the introduction of medications, Residency at the New York-Presbyterian their lives.

Maija Williams, CCTS Administrative Director, Receives Healthcare Leaders of New York Early Career Healthcare Executive Regent’s Award By Maija Neville-Williams

Administrative Director Maija Williams received The Healthcare Leaders of New York Early Career Healthcare Executive Regent’s Award at the Healthcare Leaders of New York Annual Gala and Awards Presentation June on 12, 2013.

This award recognizes individuals who have significantly contributed toward the advancement of healthcare management excellence and the achievement of the goals of the American College of Health Care Executives.

Candidates are evaluated on leadership ability, innovative and creative management, executive capability in developing their own organization and promoting its growth and stature in the community, participation in local, state, hospital and health association activities, participation in civic/community activities and projects, and participation in College activities and interest in assisting the College in achieving its objectives.

6 Clinical Scholars Program Celebrate New Graduates, Drs. Florian Klein and Giraldina Trevejo By Michelle Romanick

Dr. Florian Klein and Dr. Giraldina Treveo received Masters’ of Clinical and Translational Science degrees in June 2013. A dinner celebrating the Scholars and their mentors was held on June 10, 2013.

Dr. Florian Klein studied the function of B lymphocytes and the development of antibodies in HIV-1-infected patients, in particular antibodies with broad neutralizing activity against HIV-1 in Dr. Michel Nussenzweig’s laboratory. He plans to continue his research in Dr. Nussenzweig’s laborator as an as Assistant Professor for Clinical Investigation to further investigate Broadly Neutralizing antibodies in HIV-1 therapy.

Dr. Giraldina Trevejo’s research in Dr. Jean-Laurent’s laboratory focused on finding a new gene associated with increased risk of recurrent pneumoccocal infections in early childhood using whole exome sequencing. Once the candidate gene is identified, functional studies will be conducted. Dr. Trevejo will continue her research career as a postdoctoral Fellow in Dr. Jay Koll’s laboratory at the University of Pittsburgh Children Hospital studying the pathophysiology and increased control of pneumococcal pneumonia.

Drs. Barry Coller, Sarah Schlesinger, Giraldina Trevejo, Florian Klein, and James Krueger

7 Clinical Directors Network, CCTS, and Community Health Centers Collaborate to Study Serious Community Acquired Infection Study Progress and Preliminary Findings By Jonathan Tobin Introduction Study Design The infrastructure study enrolled 129 patients with SSTIs across the 6 FQHCs. The Rockefeller University Center The prospective observational study Of patients enrolled, 40% of wound for Clinical and Translational Science protocol was carefully planned through cultures were MRSA+, 16% of nasal (CCTS) and Clinical Directors Network a highly engaged participatory design cultures were MRSA+, 16% of wound (CDN– www.CDNetwork.org), a primary process that included the FQHC clinician- cultures were MSSA+, and 23% of nasal care practice-based research network investigators and Health Center support cultures were MSSA+. Those who were (PBRN), have collaborated closely since staff, and designed to maintain the carriers of Staphylococci in their nasal 2009 to build the Community Engaged standard clinical workflow so as not to cavity had a significantly increased Research Core (www.Rockefeller.edu/ccts/ disrupt patient care. FQHC clinical staff likelihood of having a positive wound communityengagement) , a component of identify and obtain informed consent culture for MRSA (OR=5.33 95% CI: 1.79- the NIH-funded Clinical and Translational from patients, and then the CDN research 15.88, p=0.0013) or MSSA (OR=7.93 95% Science Award (CTSA). Together, they staff complete the baseline survey CI: 2.85-22.08, p≤0.0001). Those patients developed and implemented an (including a description of CA-MRSA with an MRSA+ nasal culture were more innovative model that covers the full- symptoms, medical history and related co- likely to report influenza (OR = 7.87, 95% spectrum of clinical and translational morbidities, dermatological symptoms, CI: 2.26-27.41) and non-intravenous drug research from laboratory science (T1, T2) quality of life, health care services use, such as marijuana or cocaine (OR to clinical science (T3) and population utilization, social networks, and potential = 4.05, 95% CI: 1.24-13.29), suggesting health science (T4). They accomplished environmental exposures). A ruled digital a potential nasopharyngeal route of this by designing and conducting photo of the lesions is obtained by the transmission. Both MRSA and MSSA were rigorous comparative effectiveness FQHC clinicians before treatment, which highly resistant to penicillin, but not to research (CER) and implementation generally involves incision and drainage oxacillin (both antibiotics belong to the science studies in partnership with as per guidelines from the Center for beta lactam family). USA300 was the CDN’s member Federally Qualified Disease Control. One month after predominant PFGE strain type among Health Centers (FQHCs), with embedded the initial visit, a follow-up telephone MRSA+ cultures (85%). mechanistic studies carried out in the interview assesses antibiotic adherence, laboratories of The Rockefeller University. symptoms, and clinical response. Three Study Dissemination months after the index infection, a Community-Academic Collaboration detailed review of the patient’s electronic Dissemination activities have focused on reaching multiple audiences: practicing The Community-Acquired MRSA Project health record (EHR) is conducted to identify any follow-up visits to the FQHCs clinicians, clinical and translational (CAMP) provides an example of the robust scientists, and the public. Dissemination infrastructure Rockefeller and CDN have for SSTIs and related problems, further antibiotic prescriptions, laboratory to clinicians has involved a combination developed for conducting practice-based of grand rounds conducted onsite at research and learning in collaboration with test results, as well as any subsequent admissions to hospitals or emergency CDN Health Centers and online via FQHC clinicians and other community- CME-accredited webcasts (see www. based partners, designed to understand departments. In addition to the detailed clinical, behavioral, and epidemiologic CDNetwork.org/Rockefeller) presented the genotype and phenotype of CA- by two alumnae Clinical Scholars, Drs. MRSA in the NY Metropolitan area, as data, biological specimens of the wound, as well as nasal surveillance cultures, are Mina Pastagia, and Teresa Evering, as well well as to identify potential risk factors for as by Drs. Alexander Tomasz, Herminia CA-MRSA transmission and re-infection. sent to Bio-Reference Laboratories, a local commercial clinical microbiology lab, for de Lencastre, and Vincent Fischetti. Funded initially by a Rockefeller CCTS Preliminary study findings were presented pilot grant, and subsequently awarded bacterial species identification, as well as routine culture and sensitivity testing. Bio- at the 2013 meeting of the Association a one year infrastructure grant from for Clinical and Translational Science the NIH National Center for Advancing Reference then transports all confirmed Staphylococcal isolates, whether they are (ACTS) conference 2013 in Washington, Translational Science (NCATS), CAMP has DC by Dr. Shirish Balachandra, a clinician- brought together practicing clinicians resistant or sensitive to methicillin (MRSA and MSSA, respectively) to Dr. Tomasz’s investigator from Urban Health Plan, Bronx from six CDN FQHCs in Manhattan, NY and Dr. Maria Pardos de la Gandara, a Bronx, Brooklyn, and Westchester with Laboratory of Microbiology and Infectious Diseases at Rockefeller for confirmation, post-doctoral fellow in the Tomasz Lab. Rockefeller Head of Laboratory Dr. Another poster was presented at the 13th Alexander Tomasz and his colleagues to identification, and molecular and genetic testing, including multi-locus sequence Conference of the International Society of learn together about best practices in the Travel Medicine in Maastricht, Netherlands diagnosis and management of skin and typing (MLST), spa typing, determination of the unique SCCmec cassettes carrying (May 2013) by Nancy Jenks, FNP, a family soft tissue infections (SSTIs). A previous nurse practitioner from Hudson River study conducted by Drs. Tomasz and the resistance determinant mec A, and pulse field gel electrophoresis (PFGE). A Health Care (Peekskill NY www.HRHCare. Herminia de Lencastre had developed a org). Dr. Tobin will present the result of hospital surveillance network to study nested sub-study also examines a wider range of surveillance cultures obtained the study at the AHRQ-North American healthcare acquired MRSA (HA-MRSA) Primary Care Research Group (NAPCRG) among NYC and Westchester Hospitals, from multiple sites on the patient’s body in order to determine whether there is Annual Practice-based Research Network and the CAMP Health Centers were (PBRN) Conference in Washington selected from these same communities. clonal heterogeneity of MRSA subtypes within patients. DC (June 2013). MRSA community Continued on page 11 8 Joel Correa da Rosa, Ph.D. Joins the CCTS Biostatistics Group By Michelle Romanick

Joel Correa da Rosa, Ph.D. joined the Laboratory of Institute of Computing Center for Clinical and Translational at Federal Fluminense University. He Science (CCTS) and the Krueger Laboratory taught statistics at the undergraduate as Research Associate in Biostatistics. and graduate levels for multiple courses, Dr. Correa da Rosa assists researchers provided statistical support to researchers in the design of their experiments, in the petroleum industry, and assisted sample size evaluation, selection of researchers in diverse disciplines at appropriate statistical methodology, and the Federal Fluminense University. performance of statistical data analysis. Dr. Correa da Rosa commented on why Dr. Correa da Rosa received his Bachelor’s he was excited about joining Rockefeller degree in Statistics at the National School University, “I really like to perform data of Statistical Sciences in Rio de Janeiro, analysis and to think about statistical Joel Correa da Rosa, Ph.D Brazil, his Master’s degree in Statistics at modeling of phenomena in biology and the University of Campinas in San Paolo, health sciences. The era of Big Data brings Brazil, and his Ph.D. in Decision Support any challenges for data analysis and creates Methods at Pontifical Catholic University a tremendous opportunity for developing of Rio de Janeiro. He also attended the methodologies that could help translational Stockholm School of Economics as a science. I am looking forward to assisting visiting student during his doctoral work. researchers in CCTS to strengthen their publications with appropriate Before joining CCTS, Dr. Correa da Rosa was statistical data analysis. The application Lecturer at Federal Fluminense University of statistics in these fields fascinates me.” in Rio de Janeiro and a researcher at Active Documentation and Intelligent Design

Andrea Leinberger-Jabari, New Community Engagement Specialist By Michelle Romanick

Andrea Leinberger-Jabari, MPH joined rural long term care facilities and doula care Rockefeller University in March 2013 as the for incarcerated women and their infants, to Community Engagement Specialist for the assessment of nutrition in daycare centers. Center for Clinical and Translational Science. In this role as the Community Engagement Andrea also developed a training program Specialist, Andrea works with Rockefeller for community partners on the basics of University Center for Clinical and Translation conducting health research with academic Science (CCTS) faculty and trainees as partners. Andrea holds a BA in Anthropology well as key community partners to match from Arizona State University and earned health community needs with CCTS her MPH in Community Health Education research programs. She also works with from the University of Minnesota in 2004. CCTS leadership to shape strategic goals for the community engagement programs. She has more than 10 years of experience developing, managing, and evaluating Andrea previously was the Assistant public health programs, and has been Andrea Leinberger-Jabari, MPH Director of Community-Engaged Research recognized as an emerging leader in public Programs at the University of Minnesota’s health by the Minnesota Public Health Clinical and Translational Science Institute, Association and the Minnesota Department where she oversaw the daily operations of Health. Andrea’s research interests include of this key function. In this capacity, she using social network analysis methods to worked with academic researchers and measure community engagement, health community partners across the state disparities, and the role of community health to build relationships to develop new workers in medical homes. Andrea lives community-engaged research projects on in Westchester County with her husband, topics ranging from person-centered care in 3 ½ year old son, and their ancient cat.

9 Yale/Rockefeller University CTSA Collaborative Research Day By Michelle Romanick On May 16, 2013, 16 members of the Your Brain: Insights From Meditation broadly neutralizing antibodies (BNAbs) Rockefeller University Hospital Center Using Real-time fMRI.” He discussed in HIV-1 Therapy. BNAbs are characterized for Clinical and Translational Science improved methods to analyze mindfulness by being able to potently neutralize a (CCTS) visited the Yale Center for Clinical linking brain activation patterns during wide range of different HIV-1 strains. In the Investigation (YCCI), continuing the tradition specific meditation techniques tolaboratory of Dr. Nussenzweig, Florian Klein of annual Collaborative Research Day physiological and behavioral measures. and his colleagues were able to control HIV- meetings between Yale and Rockefeller that 1 infection in humanized mice when these began in 2008. This year’s event, like those Dr. Manish Ponda, Assistant Professor of animals were treated with a combination of in the past, provided a great opportunity Clinical Investigation in the Laboratory BNAbs. This new therapeutic approach was for trainees and junior faculty from both of Biochemical Genetics and Metabolism as effective as the combination of classical institutions to discuss their current research and Attending Physician at The Rockefeller anti-retroviral drugs. Moreover, based on the studies, develop collaborations, and discuss University Hospital presented, “Vitamin D long antibody half-life, HIV-1 infection was topics of mutual interest. Dr. Robert Sherwin, Repletion and Cholesterol: The Uncoupling controlled for an average of 60 days after Director of YCCI and Dr. James Kruger, of Epidemiology and Intervention.” He the last injection of a combination of BNAbs. Co-Director of CCTS warmly welcomed presented his data showing that while higher the attendees. The first event of the day vitamin D levels are strongly correlated with Dr. Andrew Goodman, Assistant Professor was a poster session in which 17 posters lower cholesterol levels in epidemiologic of Microbial Pathogenesis at Yale gave an were presented and discussed. This was studies conducted at Rockefeller and oral presentation of his abstract on how followed by a lively lunch-time discussion. supported by population level data obtained resident human-associated microbes in collaboration with QUEST diagnostics play critical roles in the response to The afternoon was dedicated to showed that correcting vitamin D deficiency nutrients, toxins, and pathogens. His presentations from Yale and Rockefeller with oral vitamin D supplementation research uses genomics and biochemistry faculty. Dr. David Hafler, Gilbert H. Glaser does not translate into lower cholesterol to study the processes of selection and Professor and Chairman of the Department levels. These results challenged the current competition that shape these communities. of Neurology at Yale School of Medicine, paradigm that vitamin D supplementation as well as Neurologist-in-Chief of the mimics the benefit of naturally higher Dr. Michelle Lowes, Associate Professor of Yale-New Haven Hospital spoke on the vitamin D levels. He also shared preliminary Clinical Investigation in the Laboratory of “Pathophysiology of Human Autoimmune data from his new, ongoing trial comparing Investigative Dermatology, and an Attending Diseases.” His laboratory focuses on the the effect of oral vitamin D supplementation Physician at The Rockefeller University understanding of human autoimmune to ultraviolet light therapy. In contrast to Hospital presented “Myeloid Dendritic Cells diseases, investigating naturally occurring oral vitamin D, light therapy has a beneficial in Psoriasis.” Her research studies the chronic human diseases that provide insight into effect on cholesterol levels. These new inflammatory skin disease psoriasis mainly the basic processes of T cell regulation. data may explain the paradoxical finding from a “dendritic cell-centric” point of view. His lab also emphasizes translating these that supplements fail to reproduce the discoveries into therapies for human diseases. benefits of naturally higher vitamin D levels. Drs. Krueger and Sherwin closed the event by acknowledging everyone’s Dr. Judson Brewer, Assistant Professor of Dr. Florian Klein, Chief Clinical Scholar and participation in creating another successful Psychiatry and Medical Director of the Instructor in Clinical Investigation in the collaborative event. Rockefeller will host the Yale Therapeutic Neuroscience Clinic Laboratory of Molecular Immunology gave next Research Collaboration Day in 2014. then presented “Train your Mind, Change an oral presentation on his studies using

10 Clinical Directors Network, CCTS, and Community Health Centers Collaborate to Study Serious Community Acquired Infection Continued from page 8 health education sessions have been safety, and clinical effectiveness by rapidly identify research participants who do not presented in the communities served by incorporating new clinical knowledge into have an ongoing source of health care. CAMP Health Centers. Rhonda Burgess, practice. The CAMP research team is now RN, of Manhattan’s Physician Group exploring the geographical heterogeneity A series of focus groups were also disseminated CA-MRSA information at of CA-MRSA and building a platform conducted with CAMP patients and “Cutting for a Cure,” a community health for rapid dissemination of findings by clinicians as part of a Rockefeller CCTS fair held by Denny Moe’s Superstar collaborating with other PBRNs. Under Pilot Study (PI: Dr. Rhonda Kost). The Barbershop, Harlem, NY. Dr. Onyinye the auspices of N2–PBRN the study data indicated that prevention of Okpukpara of Open Door Family Health protocol is being implemented in three recurrence was among the patients’ Center, Ossining, NY, and Franco Barsanti, additional PBRNs in Texas, Illinois, and greatest concerns. The FQHC clinician PharmD of Urban Health Plan, Bronx NY New York, including six additional FQHCs. investigators reinforced the data obtained presented health information displays at The pilot study involves collaboration from the patient groups since treating their FQHCs. Dr. Chamanara Khalida, , CDN with two established PBRNs, South Texas recurrent MRSA infections in their patients CAMP Project Manager, along with CDN Ambulatory Research Network, STARNet, is a significant clinical challenge. Among staff, including Amanda Tsang, MPH, and San Antonio TX with Christopher R. CAMP patients enrolled in the study, the Brianna D’Orazio, have presented MRSA Frei, PharmD, MSc, BCPS and ACCESS staphylococcal infection recurrence rates health education sessions and distributed Community Health, Chicago IL with were 31% and 39% for MRSA+ and MSSA+ public health educational materials at Milton Eder, PhD, as well as an “incubator” patients, respectively These data have led several health fairs and barbershops in PBRN at Lutheran Family Health Center to a pragmatic clinical trial of household NYC. Network with Nonkulie Dladla, MD MSc, staphylococcal decontamination and Brooklyn NY. family member decolonization to prevent Next Steps MRSA transmission and recurrence. In A second 2013 CCTS-funded pilot study 2012,–the Rockefeller comparative A 2013 pilot study funded by the (Rhonda Burgess, RN, Manhattan’s effectiveness research (CER) study to test Rockefeller CCTS has expanded the CAMP Physician Group, Co-PI) is reaching out interventions to reduce MRSA re-infection infrastructure, building upon the AHRQ- to barbers and beauticians in NYC who by decolonization of household members funded Center of Excellence (P30) for may see customers with skin and soft and decontamination of household Practice-based Research and Learning tissue infections. These infections pose surfaces was selected by the NIH CTSA at CDN, “N2: Building a Network of an occupational health and safety risk to as a “Use Case” for CER and received Safety Net PBRNs.” The N2–PBRN brings the “esthetic care providers” (and their the highest score among all proposals together eight established PBRNs in New submitted to the CTSA. The consortium is York City, Chicago, Boston, Portland, and families), as well as a risk of infection currently working on a formal proposal to Oakland, in addition to creating two transmission to other customers. conduct this study. “incubator” PBRNs in Washington DC Since barbershops and beauty-parlors in and Brooklyn NY. The goal of the CDN Beyond MRSA to Hepatitis C N2-PBRN is to strengthen the research many urban minority communities are and dissemination infrastructure of each often a source of health information for The CDN-Rockefeller CCTS group is collaborating PBRN so as to accelerate the low-income and immigrant populations also exploring collaborations with the generation of new clinical knowledge. It with limited English proficiency and NYS Department of Health to use the seeks to build a community of learning limited health care access, this represents established CA-MRSA research and for primary care practices in order to a novel way to disseminate public health training infrastructure to establish policies improve medical care quality, patient information about MRSA, as well as to and procedures to implement the new age-based universal screening guidelines for Hepatitis C. Dr. Charles Rice, Head of the Laboratory of Virology and Infectious Disease and a world expert in hepatitis C pathogenesis, is collaborating on this initiative.

Community Engaged Research Core

11 17 Rockefeller Investigators Complete the Center for Clinical and Translational Science Certificate Program By Michelle Romanick

On May 31, 2013, 17 investigators from The protocols that were submitted in Both courses received positive student across the Rockefeller campus completed fulfillment of the requirement of the evaluations, with 100% of the students the Clinical and Translational Science course were of exceptionally high caliber reporting that they would recommend Certificate Program sponsored by the Center and offered insights into the clinical participation in the Certificate Program. for Clinical and Translational Science (CCTS). research interests of the talented group of Ten of the 17 participants hold PhD degrees. investigators who enrolled in the program. As one student wrote, The program requires that participants The second course, “Introduction to successfully complete two courses over Scientific Techniques in Clinical and “It was a great introductory class to human the academic year. In the first course, Translational Science,” was led by Drs. Sarah subject study. Having the chance to interact ”Introduction to Clinical and Translational Schlesinger and James Krueger. This course with various investigators and staff with a Science,” the participants learn about each introduced the students to core resources lot of experience in human subject study element of a human subjects protocol available at Rockefeller University and their was very valuable. Also, writing a study (e.g., biostatistical considerations, human application to address critical problems in protocol and have a mock IRB session seems subjects protection, study design, and human biology. The students learn from to be the best way to put together what we conflict of interest) from senior staff and the Rockefeller University core resource learned from the class. I would definitely members of the CCTS in a series of tutorials leaders about the resources available recommend this course to my colleagues. that are coupled with scientific presentations and how to apply them to their research. by translational investigators describe These presentations are supplemented The Certificate Program is next scheduled for their research. With this background, by investigators who have employed the the academic year beginning in September participants create their own hypothetical technique to their human subjects research. 2014. human subjects protocols, including an The final project of the course involved informed consent form. After completing the students returning to the protocols their protocols, the participants function they developed in the first course and as a mock Institutional Review Board enhancing them by adding new techniques (IRB), reviewing each of the protocols and to augment their research design and offering suggestions to insure the optimal facilitate testing their hypotheses. design and maximizing participant safety.

2012-2013 Certificate Course partipants

12 Immunology meets Bioinformatics: Paving the way to Discoveries in Advancing Translational Medicine By Shamim Mollah Since their discovery some 30 years ago, strongly Flt3L responsive, which may relate distinct and novel target of therapeutics skin-derived dendritic cells (DC) have been them to classical DCs that have been shown aimed at enhanced cutaneous immunity. recognized as potent antigen presenting to be more useful for vaccine development. Bioinformatics approaches are employed cells with critical roles in both the to identify molecular and cellular regions initiation of adaptive immune responses CD11b-DCs are a low-frequency, that can be targeted with specific clinical and tolerance of self. The development of heterogeneous, previously uncharacterized interventions to provide better insights to vaccines and clinical therapeutics to skin migratory DC subset. This project is both the molecular and cellular basis of disease. cancers has been hindered by a lack of very fundamental—looking closely at clarity of the function and development of the cellular requirements for immune Dr. Anandasabapathy currently heads an the diverse DC subsets present in the skin priming— and highly translational, bringing independent group within Department and skin draining lymph nodes. Different a drug into the cancer arena that may of Dermatology at Brigham and Women’s/ DC subsets respond to distinct self and improve vaccines. It is also challenging— Harvard Medical School and is an Associate foreign antigen challenges, and exhibit some of the findings go against the current Physician/Instructor in Dermatology. She is different functional specialization. dogma. The bioinformatics analysis has also an Instructor in Clinical Investigation strengthened and reinforced the functional who completed her post-doctoral work A research collaboration between studies. at Rockefeller University in the laboratory Rockefeller University’s CTSA of Dr. Ralph M. Steinman and is now a Utilizing various custom-developed bioinformatics core and Dr. Niroshana (Niro) member of Dr. James Krueger’s laboratory. Anandasabapathy is currently underway computational methods and bioinformatics focusing on understanding dendritic cell tools, namely GeneSpring (GS) and Ms. Shamim Mollah is a bioinformaticist lineage of these DC subsets and their Ingenuity Pathway Analysis (IPA), we have at Rockefeller University who currently function in the setting of productive performed gene expression profiling and leads the bioinformatics analytic core immunization. This is a phase 1 clinical trial pathway analysis using development and operated under the Center for Clinical and on a hematopoietin that expands dendritic functional network analysis of individual Translational Sciences. cells, while also investigating the cellular dendritic cell subsets. Transcriptome basis for vaccine and the mechanisms in analysis suggests a close relationship mice by which this drug acts to improve of CD11b-DCs to other skin DCs, and immune responses. transcriptional and lineage relationship into other classical DCs. In particular our study builds on the observation that Langerin-CD11b-dermal This work suggests the previously DCs (CD11b-DC) are Flt3L-dependent and overlooked CD11bDCs subset may be a

Upcoming Seminars in Clinical Research Speakers

September 4, 2013 Christine Eng, MD Director, DNA Diagnostic Laboratory , Baylor College of Medicine

September 11, 2013 Robert Schwartz, MD, PhD Laboratory for Multiscale Regenerative Technologies, MIT

September 18, 2013 Juan Lafaille, PhD Professor of Pathology and Medicine, NYU

September 25, 2013 David Friedman, MD Assistant Professor of Medicine, Harvard Medical School

October 2, 2013 Michael Camilleri, MD Professor of Medicine and Physiology, Mayo Clinic

13 Clinical Scholars Welcome BBQ By Michelle Romanick

14 Rockefeller University Hospital Historical Vignette Discovering the Genetic and Evolutionary Basis of Bacterial Antibiotic Resistance By Elizabeth (Betsy) Hanson

sensing" factor, a kind of bacterial hormone to study the molecular epidemiology of excreted by individual cells that makes an drug resistant staphylococci, pneumococci entire population of bacteria receptive for and enterococci in collaboration with taking up DNA molecules carrying resistance the Laboratory of Molecular Genetics of factors. For example, pneumococcus— the Instituto de Tecnologia Química e one of the most dangerous pathogens Biológica (ITQB) in Portugal. This initiative producing pneumonia—becomes resistant was the first to demonstrate widespread to penicillin by "borrowing" pieces of foreign occurrence of multi-resistant pneumococcal DNA from other bacteria. Tomasz found that and MRSA clones in hospitals in New this enables the pneumococcus to remodel York City as well as hospitals and Day its penicillin target proteins, the so-called Care Centers in twenty different countries penicillin binding proteins, so that they in Europe, South America, and Asia. can withstand the assault of the antibiotic molecule. Analysis of this phenomenon With the arrival of the era of full genome by Tomasz and colleagues led to the sequencing the collection of thousands of discovery of a novel survival strategy of well-characterized bacterial isolates has bacteria, named antibiotic tolerance. They become a critical resource for tracing the Tomasz, Alexander later found that a single foreign genetic evolution of antibiotic resistant clones determinant, also encoding a low affinity of staphylococci during intercontinental penicillin binding protein, is the basis of In the 1940s and 1950s the first truly spread- as it was reported in a recent the wide-spectrum antibiotic resistance in effective antibiotics came into use, collaborative study with the The Wellcome methicillin-resistant staphylococci (MRSA). including penicillin and methicillin. These Trust Sanger Institute. Full genome These MRSA strains have become the drugs transformed medicine, but releasing sequencing was also used by the Tomasz lab most frequent agents of serious hospital them into the environment in enormous to identify genetic steps that accompanied and community acquired infections quantities unleashed a backlash from the the evolution of antibiotic resistance in in our era. Tomasz's group tentatively microbial world. Powerful selective pressure vivo in a patient undergoing chemotherapy identified the actual evolutionary source from antibiotics forced bacterial pathogens with the antibiotic vancomycin. of the genetic determinant conferring into a kind of accelerated evolution: mutants methicillin resistance—the so-called with altered antibiotic resistant target Alexander Tomasz, a native of Hungary, mecA gene—in another staphylococcus proteins emerged and resistance genes received the PhD in Biochemistry from species that inhabits the skin flora became "mobilized" to spread through many Columbia University (1963). He then of many wild and domestic animals. pathogenic species. That is how antibiotic- joined the laboratory of Rollin Hotchkiss resistant pathogens such as penicillin- at Rockefeller as a postdoctoral fellow. At resistant pneumococci and methicillin- Some of the most powerful antimicrobial Rockefeller, Hotchkiss and René Dubos were resistant S. aureus (MRSA) have evolved. agents target the mechanism by which pioneers in launching the antibiotic era, and Less than five decades after the introduction bacteria synthesize a cell wall, leading both had worked under Oswald Avery, who of penicillin, the rapid emergence and to unique structural changes in these identified DNA as the "transforming factor" spread of multi-resistant pathogens had molecules. The characterization of these that could change a harmless bacterium begun to pose serious problems to the changes in the bacterial surface has into a pathogenic one. Tomasz became therapy of infectious diseases worldwide; become one of the major contributions of assistant professor in 1964, associate this was the conclusion of national and the Tomasz lab to microbial cell biology. professor in 1967, and professor and head international experts that convened in a of laboratory in 1973. In 1998 he was named workshop organized by Alexander Tomasz Once human pathogens such as to an endowed chair in infectious diseases at The Rockefeller University in 1994. Staphylococcus aureus or Streptococcus honoring the late Greek microbiologist pneumoniae manage to equip themselves Plutarch Papamarkou. His achievements Tomasz has led the field in investigating with antibiotic resistance genes, they can have been recognized with the first bacterial evolution as it occurs in the real then produce antibiotic-resistant clones that Hoechst-Roussel Award in antimicrobial life, in vivo, environment of pathogenic can be identified by molecular fingerprinting chemotherapy from the American Society microbes. In the 1960s he discovered what techniques. The Tomasz lab pioneered in for Microbiology (1982) and the Selman A. later became known as the first "quorum launching the first international network Waksman Award in Microbiology (1987).

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