Spring 2015

Center for Clinical and Translational Science

e-Newsletter

Center News Rockefeller University and Clinical Directors Network Share $2.8 million Award to Better Prevent Drug-Resistant Infections in the Community By Jennifer Einstein A collaborative research team at The test in a randomized fashion whether responsible for an increasingly common Rockefeller University Center for household decontamination helps community-acquired infection. Clinical and Translational Science prevent reinfection and transmission. (Image by Janice Carr, Centers for (CCTS) and Clinical Directors Network Disease Control and Prevention.) (CDN) has received a $2.8 million The project, known as CAMP2, will be award from the Patient-Centered led by Jonathan N. Tobin, president Outcomes Research Institute (PCORI) and CEO (CDN) and co-director of to study a home-based intervention to community-engaged research and an prevent recurrence of a community- adjunct faculty member at Rockefeller, acquired drug-resistant Staphylococcal Alexander Tomasz, Dr. Plutarch aurea infection (MRSA). PCORI Papamarkou Professor and head of was established under the Patient the Laboratory of Microbiology and Protection and Affordable Care Act to Infectious Disease, and Rhonda G. Kost, fund research on clinical effectiveness. co-director of community-engaged The Community Acquired MRSA research and clinical research officer Project will enroll patients with skin MRSA up close of The Rockefeller University Hospital. infections, provide English- and An electron micrograph shows clumps “This is an innovative, patient-centered Spanish-language health education project to determine the best method materials about community-acquired of methicillin-resistant Staphylococcus drug-resistant staph infections, and aureus (MRSA) bacteria, the pathogen continued on Page 9

Memorial Sloan-Kettering Cancer Center, The Rockefeller University and Weill Cornell Medical College Form Pioneering Tri-Institutional Therapeutics Discovery Institute, Inc. (Tri-I TDI) expedite early-stage drug discovery chemists who work on TDI projects in By Michael Foley leads to novel therapeutics that will close collaboration with the project PI’s impact human health. The TDI is and their lab members. These chemists funded, in part, by a generous $15 are fully embedded in the Tri-I million gift from Lewis and Ali Sanders. community and work in TDI’s labs in the Belfer Research Building. In addition The TDI is a novel organization, to these on-site chemists, the TDI also governed by its own Board of Directors has access to other Takeda resources, drawn from the Leadership of the such as structural biology capabilities, three parent institutes. Its mission ADME/tox determinations, and virtual is to effectively develop therapeutics screening services through its groups that arise from discoveries made in located in Shonan, Japan, San Diego, basic science labs. Its focus is on the CA and Boston, MA. early stages of developing compounds that make possible all-important At present, there are seven projects “proof of concept” studies – those that in the TDI portfolio. A Scientific Michael Foley, Ph.D., Sanders Director increase the likelihood that targeting Advisory Board made up of experts in of Tri-I TDI a specific biologic pathway can biology, chemistry and drug discovery In October of 2013, Memorial favorably alter the course of a disease. and development from academics and Sloan-Kettering Cancer Center, The industry selected these from over 45 Rockefeller University and Weill Takeda Pharmaceuticals, a global applicants. These projects span a wide Cornell Medical College formed research-based pharmaceutical swath of the therapeutic spectrum, the pioneering Tri-Institutional company with a strong record of from oncology and psychiatric disease Therapeutics Discovery Institute, Inc. bringing new medicines to market is a to rare diseases. Wet chemistry work on (Tri-I TDI) and partnered with Takeda close collaborator in this effort. Takeda these projects began in July of 2014 and 1 Pharmaceutical Company, Ltd, to provides 16 highly trained medicinal they are making swift progress. continued on Page 9 C. David Allis Wins the 2015 Breakthrough Prize in Life Sciences By Zach Veilleux Launched in 2013 by a group of Internet The judges recognized Allis “for the and technology entrepreneurs, the prize discovery of covalent modifications of recognizes “transformative advances histone proteins and their critical roles toward understanding living systems and in the regulation of gene expression extending human life.” and chromatin organization, advancing A $3-million cash award accompanies the understanding of diseases ranging the Breakthrough Prize, making it the from birth defects to cancer.” Histones richest prize in the life sciences, roughly are DNA-packaging proteins, one double the Nobel Prize. component of chromatin, the material of The founders are Google’s Sergey Brin which chromosomes are composed. and Anne Wojcicki, Facebook’s Mark Over the last decade, Allis and others Zuckerberg and Priscilla Chan, Yuri and have provided evidence that suggests that Julia Milner, and Alibaba’s Jack Ma and patterns or combinations of chemical Cathy Zhang. Seth MacFarlane, executive modifications to histones represent a producer of the 2014 television series layer of gene regulation that takes place Cosmos, hosted the award ceremony, away from the DNA, an epigenetic C. David Allis, Ph.D. which also featured the actors Kate layer of regulation. Epigenetic errors For his foundational research on the Beckinsale, Benedict Cumberbatch, have been associated with cancer and unexpected regulation of gene activation Cameron Diaz, Jon Hamm and Eddie other diseases, and scientists’ growing by modifications to proteins that package Redmayne as presenters. understanding of the fundamental DNA, work with implications for many “Through his work on histonemechanisms involved holds great diseases including cancer, Rockefeller’s modifications, David has opened new promise for entirely new treatment C. David Allis has been honored with the doors of scientific understanding for approaches. Histone modifications have 2015 Breakthrough Prize in Life Sciences. colleagues around the world interested also been found to play an important role Allis, Joy and Jack Fishman Professor in penetrating the complexities of gene in cell reprogramming and are expected and head of the Laboratory of Chromatin expression,” says Marc Tessier-Lavigne, to contribute to the field of regenerative Biology and Epigenetics, was one of Rockefeller president, Carson Family medicine. six life scientists to receive the prize at Professor, and head of the Laboratory “Tracking down answers to these a gala awards ceremony in November of Brain Development and Repair. “The fundamental questions concerning gene 2014 at NASA’s Ames Research Center in Breakthrough Prize is a wonderful regulation has been deeply satisfying. Mountain View, California. confirmation of the impact of his truly More recently, too, we’ve seen that some of pathbreaking research.” our findings are leading to new treatment continued on Page 9 Jeffrey Ravetch Wins Wolf Prize in Medicine By Wynne Parry work together at National Jewish Health documentation of the importance of in Denver, and Marrack is a member of diverse receptors for the constant ‘Fc’ Rockefeller’s Committee on Scientific part of antibody molecules.” Ravetch Affairs. has studied in great detail the Fc region Since 1978, the Wolf Foundation in of many antibodies, and has showed that Israel has awarded annual prizes in the they are important in mediating antibody arts and sciences, which are presented function both in pathogenic disease and by the President of Israel. This year, five the body’s normal state. prizes were presented to seven scientists “Jeff’s work on Fc receptors has and two musicians. The three winners revealed critical knowledge of the of the medicine prize were selected for molecular biology that underlies the their work on the molecular basis of the immune system,” says Marc Tessier- immune response. Lavigne, the university’s president. “By Ravetch dissects the cellular and showing how antibodies communicate molecular mechanisms that govern the chemically with immune system cells, generation of antibody specificity and the his research is of great importance to the translation of that specificity into cellular fight against both pathogenic disease and responses. By identifying the genetic autoimmune disorders. It is gratifying to Jeffrey Ravetch, M.D., Ph.D. components that cause immune system see his pioneering work recognized with Jeffrey V. Ravetch, head of the Leonard cells to respond to specific antibodies, this prestigious international award.” Wagner Laboratory of Molecular Dr. Ravetch hopes to gain a better Ravetch graduated from Yale University Genetics and Immunology at Rockefeller understanding of how a functioning in 1973 and entered the Rockefeller University, was named a recipient of the immune system protects organisms University-Cornell University M.D.- 2015 Wolf Prize in Medicine. He shares from invaders, and how a dysfunctional Ph.D. program. He received his Ph.D. in the prize, which includes a monetary immune system attacks the body’s own 1978 from The Rockefeller University, award of $100,000, with two other tissues. where he studied under Norton Zinder immunologists, Drs. John Kappler and Ravetch’s award recognizes his and Peter Model and his M.D. from Philippa Marrack. Kappler and Marrack studies of the “heterogeneous effector Cornell University Medical College in function of antibody molecules and his 1979. continued on Page 9 2 Leslie Vosshall and Jean-Laurent Casanova Elected to the National Academy of Sciences By Wynne Parry Two Rockefeller scientists have been elected to the National Academy of Sciences. Leslie B. Vosshall, Robin Chemers Neustein Professor and head of the Laboratory of Neurogenetics and Behavior, has been named a member, and Jean-Laurent Casanova, senior attending physician, professor, and head of the St. Giles Laboratory of Human Genetics of Infectious Diseases, has been named a foreign associate. They are among 84 new national and 21 new foreign members. Established by an act of Congress, the Academy provides independent, objective advice to the federal government and other organizations on matters related to health, science, and technology. New members are Jean-Laurent Casanova, M.D., Ph.D. Leslie Vosshall., Ph.D. elected by their peers based upon Casanova seeks to identify single- Vosshall works with flies, their distinguished and continuing gene mutations responsible for “holes” mosquitos, and humans to study how achievements in original research. in the immune defenses of otherwise complex behaviors are controlled In addition to their appointments healthy children, rendering them highly by cues from the environment and at Rockefeller, both Vosshall and susceptible to specific infectious diseases. modulated by an organism’s internal Casanova are investigators with the physiological state. Howard Hughes Medical Institute.

The Robertson Therapeutic Development Fund: Providing Critical Support for Translational Science at The Rockefeller University By Bruce Conway

The Robertson Therapeutic support, the application and peer- To date, three cycles of funding for Development Fund (RTDF) was created review processes afford researchers the Proof-of-Concept awards have been in early 2014 to provide Rockefeller an opportunity to learn best practices completed. For each round, a request scientists with the resources required and considerations relevant for drug for proposals (RFP) was distributed to advance promising basic research discovery and development programs and an external panel of biotechnology projects through the steps that lead from industry experts. and pharmaceutical experts and life to breakthrough medications, new sciences investment professionals diagnostic tests, or other clinical Two types of awards have been was convened for proposal reviews. innovations. The grants, totaling $25 established through the RTDF. Proof- Recommendations to fund, in full million over 5 years are provided by the of-Concept Awards support early- or in part, or to withhold funding Robertson Foundation. stage projects aimed at identifying were made by the panelists. In the and validating potential therapeutic One year after the successful launch case of requests greater than $50,000, targets and diagnostics. Early Clinical panelists had the option of requesting of the RTDF, the initiative continues Development Awards are intended to to provide the necessary resources a more detailed and comprehensive fund IND-enabling studies such as Advanced Proposal. These proposals to enable Rockefeller researchers to manufacturing and toxicology testing, pursue important studies that are rarely were subsequently sent for review and, in some cases, Phase I clinical by an external panel and scored supported by conventional funding trials. As such, these projects require mechanisms. In addition to funding according to the standard NIH scale. 3 larger grants with a longer duration. continued on Page 10 Meet the Scholar: Peter Forgacs, MD By Michelle Romanick and returned to New York to join his examples of other physician-scientists lab full time after finishing his Clinical who have successfully built research Neurophysiology/Epilepsy Fellowship programs as physicians; 3) To provide at Brigham and Women’s Hospital, ample ‘protected time’ to experience Harvard Medical School in Boston. the full depth of conducting research and to be in the position to apply for Dr. Forgacs’ research involves independent support; 4) To have a patients who have history of severe community of physician-scientists with brain injury and remain in states that similar goals and interests. Dr. Forgacs are collectively known as “disorders stated, “All of these expectations were of consciousness.” These syndromes fully met and in many regards they include coma, a condition typically seen exceeded my expectations.” in the first few weeks after injury when the patient is not responsive and their When asked about his experience eyes are closed at all times; vegetative in the Clinical Scholars Program and state, which is a condition distinguished his future plans, Dr. Forgacs responded from coma by intermittent eye opening with the following: despite total unresponsiveness; and “Obviously there were plenty of the minimally conscious state, which learning opportunities, mostly from is characterized by intermittent, but the leaders of the program and from non-consistent responses to external my peer Clinical Scholars. Also, there stimuli. The prognosis of individual is a very positive environment in the patients in the minimally conscious hospital, where research facilitators and Peter Forgacs, M.D. state is difficult to predict and the brain nurses want to learn more about the Dr. Peter Forgacs joined the Clinical circuits involved in recovery are not scientific and medical importance of Scholars Program at the Rockefeller well understood. our study. I had many opportunities to University in 2012. Dr. Forgacs received Several recent landmark explain our research in depth to many his M.D. from the Faculty of Medicine, observational studies Dr. Schiff’s people who are involved. University of Szeged in Hungary, and group have demonstrated that some Most surprising is how much I he joined Dr. Donald Pfaff’s Laboratory such patients may recover after learned from other physician-scientists of Neurobiology and Behavior as an surprisingly prolonged periods of time who are not working in the same field as Instructor in Clinical Investigation after following their brain injuries, even I am. There are many common aspects completing his neurology residency at decades later. Thus, the main goal of of conducting research regardless of the New York Presbyterian Hospital. Dr. Dr. Schiff lab’s research is to improve specific topic and having many different Forgacs is also in Dr. Nicolas Schiff’s our understanding of the underlying ways of thinking about a problem Laboratory at Weill Cornell Medical biological mechanisms in the recovery actually broadens and improves the Center. processes of consciousness in the way I think about my own research. Dr. Forgacs began his research severely injured brain and develop Without question, the most educational career while in medical school where specific therapeutic interventions to aspect is the remarkable insight and he joined the Brain Circulation Lab improve recovery. An additional focus opinions about many different topics in the Department of Physiology and of Dr. Forgacs’ research is to apply from Dr. Coller. The program provides conducted studies on newborn piglets research concepts and methods to an ideal environment, resources and as a model for hypoxic brain injury in patients who are in Intensive Care Units educational program for clinicians newborns. He presented the result of his (ICUs) after cardiac arrest. Many of who want to be physician-scientists research at student scientific meetings these patients now receive therapeutic combined with unparalleled intellectual both locally and nationally. cooling, which improves outcomes inspiration from being part of the and survival, but make it even more Rockefeller Community. Dr. Forgacs was interviewed by difficult to predict which patients will Dr. Nicolas Schiff for the Neurology recover consciousness. Therefore better I plan to continue to work with Drs. Residency at Cornell and immediately methods are needed to understand Schiff and Pfaff and conduct research became interested in Dr. Schiff’s how to measure the integrity of at Rockefeller University Hospital. My research on neurophysiological specific brain regions that support goal is the same as it has been since mechanisms of arousal and forebrain consciousness recovery and to correlate medical school – to be an excellent integration as well as clinical studies these measurements with outcomes. ‘traditional’ academic neurologist. I of the pathophysiology of impaired believe there is a great need for people consciousness. Dr. Forgacs was excited Dr. Forgacs had four specific like me, a physician who is a scientist about the approach and methods Dr. expectations from the Clinical Scholars (and vice versa) despite the increasing Schiff was bringing to understand Program: 1) To further advance his hurdles this choice for a career path brain functions in patients with severe career as a physician-scientist by involves.” brain injury and the concepts of how providing educational activities related consciousness recovers after brain to conducting clinically-relevant injury. Dr. Forgacs began to work in Dr. research projects involving human Schiff’s laboratory during his residency subjects; 2) To experience positive 4 The Rockefeller University Center for Basic and Translational Research on Disorders of the Digestive System Hosts First Gut Microbiome-Brain Interaction Symposium By Daniel Mucida The term microbiome was initially On October 23, 2014, a very diverse is known about the mechanisms and coined by Dr. Joshua Lederberg, former set of nervous system investigators specific mediators responsible for the Rockefeller University President and 1958 gathered at The Rockefeller University beneficial or detrimental effects exerted Nobel laureate to define “the ecological to discuss the current understanding of by bacterial species or groups of bacteria community of commensal, symbiotic, and how gut microbes can influence central in these models. For instance, it is possible pathogenic microorganisms that literally nervous system (CNS) development and that circulating microbiota-derived share our body space”. behavior. Investigators from American, metabolites could directly influence Although the interest of the scientific Canadian and European universities the CNS, or alternatively, activation community in the microbiome is thus presented seven seminars on recent of the immune system, or additional not new, there has been a recent burst in findings in both model organisms and indirect mediators could be responsible. microbiome research as a consequence humans. A recent study, also conducted by of rapid advances in analytical and DNA Using DNA sequencing data from Dr. Hsiao and her group, may shed light sequencing tools to study microbial the gut microbiome, investigators on this question since they found that communities that inhabit our intestine. including Drs. Jun Huh (University the gut microbiota plays an important The pioneering studies of theof Massachusetts), Emeran Mayer role in the regulation of a major microbiome by Dr. Jeffrey Gordon and (UCLA) and Christopher Lowry neurotransmitter, serotonin, and that this colleagues at Washington University (University of Colorado) showed pathway could impact several aspects of have generated an increased interest correlations between gut microbial host physiology. Additional mechanistic in the possible role of the microbiome colonization and brain development studies that better define mediators of in different bodily functions.and behavior. Dr. Jane Foster from the microbiota-brain interaction, as It is estimated that for each human McMaster University described recent well as more precise identification of cell, 10 bacterial cells occupy our body. findings linking anxiolytic behavior the bacterial species and host cell types Roughly 500–1,000 bacterial species and reduced microbiota. Dr. Tracy Bale involved in these interactions, are needed exist in our microbiome, with enormous from the University of Pennsylvania to further advance this very interesting person-to-person variation. Importantly, expanded this analysis to vertical interdisciplinary field of research. different microbial composition between transmission of maternal microbes to The symposium raised a number individuals or groups of individuals has offspring, studying its consequences to of important and challenging questions been associated with susceptibility to the neurodevelopment of newborns. and made clear the enormous potential several disease processes. In particular, Dr. Elaine Hsiao from the California of this novel area of brain research. One research performed in recent years Institution of Technology described a indication of the interest in this field has demonstrated a clear impact of role for commensal bacteria in murine comes from noting that more than 200 microbial colonization on the nervous models of autism in which oral exposure enthusiastic students, investigators, staff, system, sociability and the behavior to certain commensal bacteria improved and faculty attended the event. This augers of humans and model organisms. several behavioral defects in mice well for many additional novel discoveries Curious about these recent findings, subjected to maternal-induced activation as this area of research blossoms. Professors Torsten Wiesel and Bruce (MIA), a model of autism-related McEwen proposed hosting a symposium disorders. While the careful observations on the possible influence of themade by the investigators demonstrated microbiome on different brain functions. dramatic behavioral effects, very little

5 Manish Ponda, M.D. Receives 2015 Clinical Scientist Development Award (CSDA) from the Doris Duke Charitable Foundation By Michelle Romanick Dr. Manish Ponda received the 2015 Clinical Scientist Development Award (CSDA) from the Doris Duke Charitable Foundation to support his research “Understanding the mechanisms behind the disparate actions of endogenous vitamin D vs. vitamin D supplements on the lipid metabolism: a rational step towards optimizing treatment of vitamin D deficiency.”

The CSDA program is part of the Doris Duke Charitable Foundation strategy to develop careers of physician- scientists. It has supported 234 investigators in their transition to independent R01 grant funding since its establishment in 1998. The CSDA provides researchers with the protected time and resources necessary to build their future research programs. The 2015 Clinical Scientist Development Awards are scheduled to commence on July 1, 2015. Ana Emiliano, M.D. Receives a KO8 Clinical Investigator Award By Michelle Romanick Dr. Ana Emiliano, former Clinical model of sleeve gastrectomy and is using Scholar and member of the Rockefeller it in combination along with state-of- Early Phase Physician Scientists the-art molecular biology techniques. (REPPS), received an NIH funded Mentored Clinical Scientist Research Current evidence indicates that the Career Development Award (K08) in surgery not only leads to mechanical May. The K08 award provides five years alterations in the gastrointestinal of salary support, as well as funds for tract, but also promotes molecular research-related costs, for an intensive, adaptations in brain regions associated supervised research career development with energy homeostasis, such as the experience in translational research. hypothalamus and specific centers Dr. Emiliano’s project is entitled in the hindbrain. In her study, obese ‘Tracing the origins of sleeve mice undergo sleeve gastrectomy and gastrectomy’s glycemic effects.’ Her then changes in neuronal signaling in mentor is Dr. Jeffrey Friedman and specific brain regions are analyzed. Her Head of the Laboratory of Molecular goal is to identify neuronal populations Genetics. She is studying the molecular controlling glucose regulation and mechanism fascinating observation energy balance that are specifically that sleeve gastrectomy rapidly leads to recruited by sleeve gastrectomy. Ana Emiliano, M.D. improvement of glucose homeostasis, Dr. Emiiano is also studying novel before any meaningful weight loss. Dr. monogenic causes of obesity Emiliano hasa developed a A mouse

Robert B. Macarthur, New Director of Pharmacy By Michelle Romanick of hospital pharmacy and drug primary task was to create a GMP development as a Pharmacy Director. compliant investigational drug packaging Most recently he served as Vice and distribution department, to produce President of Clinical Development drugs for clinical trials, which entailed at Pharmaceutics International, Inc. working with formulation scientists, (Pii), an FDA licensed, contract drug analytical chemists, investigators, manufacturing organization that statisticians, and others to devise operates under Good Manufacturing formulation, packaging, labeling and Practices (GMP), in Hunt Valley MD. blinding methods. Most often these Pii manufacturers both commercial and studies require a comparison of a marketed investigational drug products that are drug product with both an active test distributed to the US, Europe, and Asia. product and a placebo. All three products Prior to his position at Pii, Dr. need to be characterized, per GMP, for Macarthur directed the Research identity, purity, activity, and stability over Pharmacy at Columbia University. time. Products also need to be packaged Robert B. Macarthur, PharmD He remains affiliated with Columbia and labeled in an identical manner as Robert B. Macarthur, PharmD, as a lecturer in the Department of well as blinded and randomized. When MS joined the Rockefeller University Biostatistics, and currently teaches devising packaging plans, we would Hospital in May 2015 as the Director of a semester long graduate course always consider ways to simplify product Pharmacy. Dr. Macarthur received his entitled, “New Drug Development: management for the clinical sites while BS in Pharmacy from Rutgers University, A Regulatory Overview” as promoting patient safety and compliance. New Jersey, his PharmD from St. part of their Clinical Research My second task involved planning John’s University, New York and MS in Methods Track graduate program. and overseeing the clinical trials Biostatistics from Columbia University. Pii is a drug manufacturing performed to support the company’s Since 1988, Dr. Macarthur has company, which produces oral, topical, own products, aimed at gaining FDA 6 work within the interrelated fields and injectable products. Dr. Macarthur’s continued on Page 11 Beatrice Renfield Lectureship in Research Nursing By Rita Devine The Rockefeller University Hospital and first generation immigrants, numerous national and international and The Heilbrunn Family Center for who are at the highest risk for illness awards and honors, including the Research Nursing hosted the annual but often have the least access to Egyptian Medal of Excellence and Beatrice Renfield Lecture in Research proper health care. She emphasized an Honorary Doctorate of medicine Nursing on March 3, 2015 in the the challenges faced by health care from Linkoping University, Sweden. Carson Family Auditorium. This professionals who provide that care. The lecture was attended by 98 year’s speaker, Afaf Meleis, Ph.D., Dr. Meleis is a world renowned guests, including nurses from the New Dr.P.S. (hon), FAAN; Dean Emerita nurse scientist and medical sociologist. York region and nursing students. In and Professor of Nursing and Sociology Her research has helped to advance addition, many people viewed Dr. at the University of Pennsylvania knowledge in global health, women’s Meleis’s presentation via webcast School of Nursing presented “NextGen health, culturally-competent practice, provided through the Clinical Directors Health Care: The Stars are Aligned”. and the development of the nursing Network (CDN). The webcast is The presentation focused on the discipline. She is the author of available through the CDN website experiences of those most burdened by more than 200 publications on under the CCTS Webcast Series section. societal inequities, in particular women these subjects and is the recipient of Sue Widmann, New Director of Nursing and Patient Care Service By Michelle Romanick Susan Widmann joined Rockefeller implementing a system-wide electronic University Hospital as the Director medical record system. of Nursing and Patient Care Services Prior to being the Director in May 2015. Ms. Widmann received of Quality and Patient Safety, her Baccalaureate Degree in Nursing Ms. Widman was the Director of from the University of Michigan and Ambulatory Service at Children’s her Master’s Degree in Public Health Hospital of Wisconsin, where she from Harvard School of Public Health. was responsible for 23 clinics at four Ms. Widmann was formerly at geographic sites with 230 full time Children’s Hospital of Wisconsin employees and an annual growth rate in Milwaukee as the Director of of 10%. A key success of that position Quality and Patient Safety where was the design, planning, and project her responsibilities included quality, oversight for the organization’s first patient safety, infection control, and major off-site medical office building. regulatory compliance. She also created The 80,000 square foot building, and implemented a strategic quality dedicated to pediatric specialized Sue Widmann, R.N., M.P.H. improvement plan for the organization, services, including a full imaging suite, and served as a key member of opened on time and under budget. the leadership team charged with continued on Page 11 Yupu Liang, New Director of Research Bioinformatics in the Center for Clinical and Translational Science and a PhD in Computer Science University community. She leads By Michelle Romanick from the Graduate Center, City the University’s Bioinformatics/ University of New York in 2014. Biostatistics Working Group, which Prior to joining Rockefeller includes many of the bioinformatics University, Dr. Liang was a senior and biostatistics experts on campus. bioinformatics engineer at Memorial The Work Group’s mission is to Sloan-Kettering Cancer Center where share research expertise, develop she was responsible for developing educational programs, and advise analytical pipelines for both array the University on strategic planning and high throughput sequencing for bioinformatics resources. data. She also taught in the Tri-I When asked about future Bioinformatics and Computational developments she envisions for the Workshops and collaborated Research Bioinformatics program, Dr. with individual investigators on Liang replied, “The next big project bioinformatics-related projects, for the group is the development of including The Cancer Genome Atlas. a flexible platform that will enable In her current leadership role, phenotype recording, phenotype- Yupu Liang, Ph.D. Dr. Liang oversees the bioinformatics genotype analysis, and user-friendly Dr. Yupu Liang was promoted to support services of the CCTS. She has dynamic visualizations. We will Director of Research Bioinformatics of particular expertise in ontology-back also focus on state-of-art high- the Center for Clinical and Translational human phenotyping projects, high- throughput sequencing analysis. Last Science (CCTS) on December 16, throughput DNA sequencing data but not least, we want to promote 2014. Dr. Liang received a Bachelor analysis, RNA expression analyses, and and develop the synergy between of Science degree in Biochemistry bioinformatics education for Clinical bioinformaticians and investigators.” from the Nanjing University in 1998 Scholars and the wider Rockefeller 7 New Clinical Scholars Set to Join the Center for Clinical and Translational Science (CCTS) By Michelle Romanick

On July 1, 2015, five new Clinical Scholars will join the Rockefeller University Clinical Scholars Program. They are: Drs. Kemal Akat, Patrick Brunner, Yehuda Cohen, Isaac Marin-Valencia, and Djin-Ye Oh. Additionally, with support from the CCTS, Benjamin Ungar, a 3rd year medical student from the Icahn School of Medicine at Mount Sinai in Dr. James Krueger’s laboratory will continued in the Center’s Year-Off Training Program for Graduate or Medical Students in Clinical and Translational Science, and with support from the Sackler Center for Biomedicine and Nutrition. Alexander Gomez, a 3rd medical student from the Icahn School of Medicine at Mount Sinai will join Dr. Paul Cohen’s laboratory to study the role of thermogenic fat in mediating outcomes of bariatric surgery patients. Below are brief biographies and descriptions of research interests of the new scholars.

Kemal Akat, MD, PhD Mentor: Dr. Thomas Tuschl Laboratory: Laboratory of RNA Molecular Biology

Dr. Kemal Akat received his MD from the Faculty of Medicine, Heidelberg University and his PhD from the German Cancer Research Center in Heidelberg. He completed his Internal Medicine residency at the University Medical Center of the Johannes Gutenberg University Mainz and Postdoctoral Research Fellowship in the Laboratory of RNA Molecular Biology at The Rockefeller University. As a Clinical Scholar in Dr. Tuschl’s laboratory, Dr. Akat is the role of RNA and RNA-regulatory proteins in the development of human diseases, especially cardiovascular disorders. He usese state-of-the art RNA-sequencing technologies to detect changes in gene expression and transcript processing in human clinical samples, and to define signatures of diagnostic or prognostic value. Animal models and basic RNA molecular biology supplement his studies on clinical samples to better understand disease mechanisms. A particular focus will be on cross-linking and immunoprecipitation (CLIP- sequencing) studies of RNA-binding proteins to identify targets and target sites of microRNAs and RNA-binding proteins.

Patrick Brunner, MD Mentor: Dr. James Krueger Laboratory: Laboratory of Investigative Dermatology

Dr. Patrick Brunner received his MD from the Medicine University of Vienna in Austria. He completed his Dermatology and Venereology residency at the Medical University of Vienna. As a Clinical Scholar in Dr. Krueger’s laboratory, Dr. Brunner will study inflammatory skin diseases, including psoriasis and atopic dermatitis, and human mechanistic studies elucidating key pathophysiological steps in disease development and maintenance as a means to identify potential therapeutic targets.

Yehuda Cohen, MD Mentor: Dr. Michel Nussenzweig Laboratory: Laboratory of Molecular Immunology

Dr. Yehuda Cohen received his MD from Stony Brook University School of Medicine He completed his Internal Medicine residency at Montefiore Medical Center in New York and his Infectious Disease Fellowship at Beth Israel Deaconess Medical Center in Boston. Dr. Cohen will study novel strategies for the prevention and treatment of HIV infection, with a particular focus on candidate HIV vaccines and the use of broadly neutralizing monoclonal antibodies for the prevention and eradication of HIV infection.

Isaac Marin-Valencia, MD Mentor: Dr. Joseph Gleeson Laboratory: Laboratory of Pediatric Brain Disease

Dr. Isaac Marin-Valencia received his MD from the University of Las Palmas de Gran Canaria in the Canary Islands, Spain. He completed his Pediatric residency at the University of Barcelona and the University of Texas Southwestern Medical Center in Dallas, where he also completed his Pediatric Neurology residency. Dr. Marin- Valencia will study the cellular and molecular mechanisms of neurogenetic conditions in children, from structural defects to metabolic disorders that afflict the developing brain, with the goal of designing better diagnostic methods and therapies that can meaningfully improve children’s wellbeing and psychomotor development.

Djin-Ye Oh, MD, PhD Mentor: Dr. David Ho Laboratory: Aaron Diamond AIDS Research Center

Dr. Djin-Ye Oh received her MD from Freie Universitaet and her PhD from Humboldt University in Berlin and Robert Koch- Institut in Berlin. She completed her Medical internship at Vivantes Auguste Viktoria Hospital and Microbiology residency at Charite University Medical Center in Berlin, Germany. She completed her Pediatric Infectious Diseases Fellowship at New York University Medical Center and Pediatric Infectious Diseases Research Fellowship at Boston Children’s Hospital. Dr. Oh will study the molecular diversity of RNA viruses and the genetic and other mechanisms underlying the variation of the human immune response to viral infection, with the goal of developing novel approaches to prevent and treat HIV-disease. 8 Rockefeller University and Clinical Directors Network Share $2.8 million Award to Continued from page 1 Better Prevent Drug-Resistant Infections in the Community to prevent recurrence of community- review process by a committee working with Clinical Directors acquired MRSA,” says Barry Coller, composed of clinical scientists, patients, Network and The Rockefeller director of the Center for Clinical and clinicians and other stakeholders. University to share the results.” Translational Science and physician- “This project was selected for PCORI in-chief of The Rockefeller University PCORI is an independent, nonprofit funding not only for its scientific merit Hospital. “By focusing on what organization authorized by Congress in and commitment to engaging patients patients and clinicians identified as 2010 to fund patient-centered clinical and other stakeholders, but also for its their highest priority in combating comparative effectiveness research that potential to fill an important gap in our this disease, we are confident that we will provide patients, their caregivers health knowledge and to give people are devoting our scientific expertise and clinicians with evidence-based information to help them weigh the to the community’s major concern.” information needed to make better- effectiveness of their care options,” said informed healthcare decisions. PCORI The PCORI award is among $102 PCORI Executive Director Joe Selby. has approved $671 million to support million committed this fall to projects “We look forward to 360 research studies and initiatives selected from among 409 proposals. following the study’s progress and since it began funding research in 2012. Awards were made through a competitive Memorial Sloan-Kettering Cancer Center, The Rockefeller University and Weill Cornell Medical College Form Pioneering Tri-Institutional Therapeutics Discovery Institute, Inc. (Tri-I TDI) Continued from page 1 from oncology and psychiatric disease the community, the TDI negotiated a Over the next several months, the to rare diseases. Wet chemistry work on groundbreaking deal with Schrödinger, TDI will be expanding its mission these projects began in July of 2014 and the leading provider of high quality into biologics and is preparing to they are making swift progress. computational chemistry and biology support the discovery and development The Sanders Innovation and software. This agreement provides of therapeutic antibodies. The Education Initiative is a key component free access to the full capabilities of organization is recruiting an expert of the TDI. In partial fulfillment of this software package to the Tri-I industrial partner in this area and is this mission, the TDI launched the community for 5 years. To ensure in the process of securing lab space Tri-I TDI Sanders Seminar Series that users in the community are fully and leadership for this new initiative. and hosted thought leaders in drug trained on the software and have the As the Tri-I TDI continues discovery and translational medicine, opportunity to take full advantage of to grow its capabilities in new including Dr. Richard Lerner from its powerful capabilities, the TDI has and exciting ways, it will bring Scripps Institute in San Diego and hosted and will continue to host a series transformational change to the process Dr. Joel Scherer from Lilly Chorus. of training events lead by applications of developing novel therapeutics scientists from Schrödinger. To bring innovative technology to on New York’s Upper East Side. C. David Allis Wins the 2015 Breakthrough Prize in Life Sciences Continued from page 2 approaches for difficult diseases,”held academic positions at Baylor College the 2007 Gairdner Award, the 2004 Wiley says Allis. “It is an amazing honor for of Medicine in Texas and at the University Prize, the 2003 Massry Prize, and the 2002 this work to be recognized by such an of Virginia before joining Rockefeller in Dickson Prize in Biomedical Sciences. extraordinary prize and it only increases 2003. As a winner of the Breakthrough my gratitude for the opportunity I’ve had He is a member of the National Prize, Allis joins Rockefeller colleagues to pursue a career in science.” Academy of Sciences and the American Cori Bargmann and Titia de Lange, who Allis received his Ph.D. in 1978 from Academy of Arts and Sciences. He is the were among the inaugural group of prize Indiana University and did postdoctoral recipient of the 2011 Lewis S. Rosenstiel awardees in 2013. work at the University of Rochester. He Award, the 2008 ASBMB-Merck Award, Jeffrey Ravetch Wins Wolf Prize in Medicine Continued from page 2 He completed his postdoctoral research Ravetch’s previous awards include the Academy of Sciences and the Institute of at the National Institutes of Health with Canada Gairdner International Award in Medicine. Dr. Philip Leder, where he cloned the 2012, the Coley Award from the Cancer The Wolf Prize is considered one of immunoglobulin heavy chain genes and Research Institute in 2007, the American the most prestigious prizes in medicine, began his career-long interest in antibody Association of Immunologists-Huang along with the Nobel Prize, the Albert function. In 1982 Ravetch joined the Foundation Meritorious Career Award Lasker Award and the Canada Gairdner faculty of Memorial Sloan-Kettering in 2005, the Lee C. Howley Sr. Prize International Award. The previous Cancer Center and in 1984 also became for Arthritis Research in 2004 and the Rockefeller recipient of the Wolf Prize a guest investigator in Rockefeller’s Burroughs Wellcome Fund Award in in Medicine was Maclyn McCarty in Laboratory of Cellular Physiology and Molecular Parasitology in 1986. He is 1990. Three Rockefeller faculty have Immunology. He returned to Rockefeller a fellow of the American Academy of been recipients of the Wolf Prize in in 1996 as professor and head of Arts and Sciences and the American Physics: Mitchell Feigenbaum and Albert laboratory and was named Theresa and Association for the Advancement of Libchaber in 1986 and George Uhlenbeck Eugene M. Lang Professor in 1997. Science and a member of the National in 1979. 9 The Robertson Therapeutic Development Fund: Providing Critical Support for Translational Science at The Rockefeller University Continued from page 3

As seen in the Table on page anti-cancer therapeutic and one for Therapeutics Discovery Institute 3, a total of 54 Proof-of-Concept the prevention of HIV infection. (Tri-I TDI), a joint program with Awards have been approved for Memorial Sloan Kettering Cancer Since the Fund’s inception, RTDF funding to date. Pilot grants were Center and Weill Cornell Medical has provided ~$10 million in awards awarded for 38 projects that include College designed to advance small to Rockefeller scientists. In total, 56 22 early-stage projects, 8 screens molecule drug discovery programs. proposals submitted by researchers in 28 for therapeutic molecules, 4 novel The RTDF supports projects in all Rockefeller labs have received funding. diagnostic projects, 3 vaccine projects, stages of the drug development process and one cell therapy approach. All Rockefeller Clinical Scholars, as well as biological products and In addition, sixteen Advanced Postdoctoral fellows and research diagnostics that are not part of Tri-I Proof-of-Concept (POC) grants faculty are eligible for the awards, TDI’s current mission. In this way, the were funded. The scope of funded which are distributed according to a RTDF affords Rockefeller researchers Advanced POC projects covers a schedule based upon the successfull an opportunity to leverage the most range of projects aimed at developing completion of agreed-upon milestones. promising findings made in the novel therapeutics, vaccines, The Robertson Therapeutic University’s labs to ultimately impact biomarkers and medical devices. Development Fund serves as a model the patient. For more information on for academic translational research this exciting program, please contact In May, 2014, two Early Clinical Dr. Bruce Conway at 212-327-8376. Development Awards were also initiatives and represents an important approved for funding; one for a novel complement to the Tri-Institutional Featured RTDF Projects of the safety, pharmacokinetics and of attachment of HIV to host cells, antiretroviral activity of 101074v mAb 3BNC117 shows activity against 195 in HIV-infected and HIV-uninfected out of 237 HIV strains. volunteers. Dr. Caskey’s work was recently The Robertson Foundation has reported in the journal Nature provided key support for Marina (Nature online: April 8, 2015) and Caskey MD as an investigator and her demonstrates that the experimental efforts to advance highly neutralizing therapy can dramatically reduce the monoclonal antibodies against HIV-1 amount of virus present in patient’s from the laboratory to the Clinic at the blood. This important observation, Rockefeller University Hospital. The brings fresh optimism to the field of flexibility and forward looking nature HIV immunotherapy and suggests of the RTDF support has allowed Dr. new strategies for fighting or even Caskey, working with Drs. Michel preventing HIV infection. With Nussenzweig and Sarah Schlesinger, continuing support from the RTDF, Dr. Dr. Marina Caskey (Nussenzweig Lab) to bring 3BNC117, a new generation Caskey and the Zanvil Cohn Clinical Early Clinical Development Award: of broadly neutralizing antibodies, Vaccine Center team are working to Production of monoclonal Antibody 10- into the clinic in an expeditious bring the next highly neutralizing 1074v for clinical study use and a phase manner. 3BN117 targets the CD4 monoclonal antibody, 10-1074, into 1 open label, dose-escalation study binding site of the HIV envelope, and the clinic. the CD4 receptor is the primary site

“I joined Rockefeller as a Clinical Scholar to understand why kidney disease accelerates atherosclerosis. Encouraged to “follow the science”, our work identified a novel role for coagulation factor XII (FXII) in immune cell migration, and we began to appreciate the potential role of FXII in immune-mediated disease. There are no FXII inhibitors available for clinical use, and transitioning from experimental science to drug development is high risk and often beyond the scope of traditional funding mechanisms.

The RTDF has proven to be an invaluable catalyst for accelerating the development of our FXII inhibitor technology. Furthermore, as a physician-scientist, advancing a basic science discovery into the pipeline of therapeutic development is intensely gratifying. With Bruce’s help, we’ve built a team of experienced consultants and veteran medicinal chemists to take us through lead identification and optimization. The RTDF has effectively transformed the lack of a factor XII inhibitor from a barrier into Dr. Manish Ponda (Breslow Lab) Proof-of- an incredible opportunity.” Concept Award: Inhibition Factor XII: targeting a novel mechanism of inflammation in immune-mediated disease. 10 Robert B. Macarthur, New Director of Pharmacy Continued from page 6 drug approvals. This task involved serving patients and research staff, and Pharmacy Service to contribute to that establishing a regulatory strategy and ensuring ongoing compliance with effort via the thoughtful application drug development pathway, guided by state and federal laws, and accreditation of pharmacy practice, and regulatory literature, FDA guidance documents, FOI agency requirements. Dr. Macarthur will science. We live in a time where the information requests, and other sources. also be supporting the overall clinical drug development paradigm is rapidly The Pharmacy at Rockefellerresearch program at Rockefeller via changing, incorporating both large University has heretofore been participation in the Navigation Program (“blockbuster”) and small (orphan managed by New York Presbyterian and the Institutional Review Board. diseases and personalized medicine) Hospital (NYPH). Moving forward When asked what is his population therapeutics. I intend Dr. Macarthur will be establishing a vision and plans for the Pharmacy to develop a pharmacy program at pharmacy that is a department within Department, Dr. Macarthur responded, Rockefeller that will maximally support Rockefeller University. His primary “NYPH has done a great job over Investigators to accomplish both their responsibilities involve overseeing many years at Rockefeller University, and study objectives, and, where appropriate, the development of the Rockefeller I look forward to both continuing and their goals to move products further University Pharmacy thru its transition building on that tradition. The clinical down the “critical path” toward drug from NYPH. As Pharmacy Director, trials performed at Rockefeller bridge regulatory approval. The objective of additional responsibilities include fundamental science with research on all of this being to get novel, safe and maintaining safe dispensing practices, human disease. I expect the Rockefeller effective medications to patients, faster.”

Sue Widmann, New Director of Nursing and Patient Care Service Continued from page 7 When asked what her vision and future plans for the nursing department, Ms. Widmann replied, “Our goal is to insure that as clinicians we promote a safe and effective environment that actively supports clinical care. Nursing will effectively partner with the full research team to support the research process and insure good clinical practice. We will provide compassionate, safe, and patient-centered care while maintaining clinical research standards.” We welcome Ms. Widman to The Rockefeller University Hospital clinical community. Masterminding Bacterial Classification - Centennial Vignette By Elizabeth (Betsy) Hanson in use today, laid the groundwork for understanding the clinical course of these diseases and how they are transmitted. A turning point came in the mid- 1920s when Lancefield recognized that streptococci carry a protein on their cell surface that is correlated with virulence. Lancefield called this the M protein, and classified types of streptococci based on variations in this protein, as determined by their reactions with different antisera. She also found that the M protein prevents human white blood cells from engulfing and destroying streptococci unless an antibody is present to neutralize this effect. This Lancefield, Rebecca explained why repeated strep throats, for example, are so common in childhood— Courtesy of the Rockefeller Archive Center immunity to one streptococcus does not prevent infection with another type. BA from Wellesley College (1916) and During World War II, Lancefield’s the PhD from Columbia University laboratory became known as the (1925). She began her work on hemolytic “Scotland Yard of streptococcal streptococci in the laboratory of Oswald mysteries,” as she worked with the Naval T. Avery in 1918. She left the next year, Lancefield, Rebecca after Avery’s project was completed, but Courtesy of the Rockefeller Archive Center Medical Center, the Army’s Board for Investigation of Epidemic Diseases, and returned to the Rockefeller Hospital in others to type bacterial cultures isolated 1922 as an assistant in the laboratory of When Rebecca Lancefield (1895- Homer Swift. She remained at Rockefeller 1981) began studying the bacteria from patients in military hospitals. The evidence from the thousands of cultures for the rest of her career, rising to the known as hemolytic streptococci, no one title of professor in 1958. Lancefield recognized that these microbes caused that she typed informed later studies on streptococcal epidemiology and the served as president of the Society of common—and dangerous—human American Bacteriologists and of the diseases such as “strep throat,” scarlet mechanism by which rheumatic fever develops after a streptococcal infection American Association of Immunologists. fever, rheumatic fever, acute kidney She was elected to the U.S. National disease, and impetigo. Beginning in with scarlet fever. The data also led to a practical immediate recommendation Academy of Sciences, and her work 1918, and continuing over the course of was recognized by, among other awards six decades, Lancefield devised a system for less crowded barracks to reduce the chance of infectious outbreaks. and honorary degrees, the American for classifying the dozens of types of Heart Association Achievement Award. 11 streptococcal bacteria. This system, still Rebecca Lancefield received the