Dean’s Quarterly SPRING 2011 accelerating science, advancing medicine

Becoming an Engine of Discovery I am pleased to outline the strategic plan for the Center for Discovery and Innovation (CDI) at The Mount Sinai Medical Center. This entity, designed to capitalize on the unprecedented opportunities of 21st century biomedicine, will bring together some 30 renowned translational scientists, many of whom are successful drug developers and patent-holders already, with the charge of translating discovery into therapeutics and generating new intellectual property.

Under the direction of a senior leader with Experimental Therapeutics Institute in five key international stature in translational medicine areas: small-molecule drug discovery, monoclonal and the successful development of therapeutic antibodies and purified proteins, high-content interventions, the CDI discovery group will screening/RNAi, induced pluripotent stem cells, identify the most promising research within all of and systems pharmacology and network analysis Mount Sinai’s disease-focused institutes with the facilities. goal of illuminating new disease targets and the The success of the CDI enterprise and the Dennis S. Charney, MD, is the Anne and Joel Ehrenkranz molecules that treat those targets. scientists it recruits and supports will ultimately Dean of Mount Sinai School of Medicine and the Executive Vice President for Academic Affairs of The Mount Sinai This new era of growth will span years and will be measured by the discoveries made, and the Medical Center. require great institutional commitment and applications developed, to predict, prevent, investment, and the results will be breathtaking. and treat disease. I look forward to sharing with The CDI is structured to focus on five areas that you the progress and results of CDI throughout To learn more, visit www.mountsinai.org/Charney represent the most pressing global disease burden: the coming years. cardiovascular disease, cancer, neurological See the Drug Discovery Roadmap on page 2. disorders, immune disorders, and virology/ core facilities of the experimental therapeutics institute (ETI) disease focus areas vaccines. To explore these of eti core facilities areas in the greatest depth 5 Small- Monoclonal High-content Induced Systems cardiovascular disease and breadth possible, we molecule drug antibodies screening/ pluripotent pharmacology Cancer will expand the facilities discovery and purified RNAi stem cells and network neurological disorders and capabilities of our proteins analysis immune disorders Virology/Vaccines

INSIDE THIS ISSUE distinguished by service 2 Medical Milestones Department of Rehabilitation Medicine Anniversary 3 Research Frontiers In 1910, The Mount Sinai Medical Center established one Kristjan T. Ragnarsson, MD, Lucy G. Moses Professor 3 Young Pioneers of the nation’s first departments devoted to rehabilitating and Chair of the Department of Rehabilitation Medicine, 4 New Faces patients with disabling injuries and medical conditions. Today, and Wayne A. Gordon, PhD, the Jack Nash Professor 5 Philanthropy the Department of Rehabilitation Medicine is consistently of Rehabilitation Medicine, and an Associate Director 5 Patient-Centered Care ranked one of the best in the nation by U.S. News & World of the Department of Rehabilitation Medicine, lead an Report in its annual Best Hospitals survey. The Department interdisciplinary team of professionals. 6 Photo Essay commemorated its 100th anniversary in November. Continued on page 2 7 Commentary accelerating science medical milestones The Drug Discovery Roadmap A New Alternative to Open Heart Surgery

Mount Sinai and other academic Three leading physicians at Mount Sinai Heart Approximately 100,000 people in the United medical centers are the new have performed the first U.S.-based percutaneous States are diagnosed with severe aortic stenosis implantation of a novel device that replaces a each year, but one-third of them do not qualify engines of research and discovery diseased aortic heart valve, providing a viable for surgery due to their advanced age, the fact for the pharmaceutical industry. treatment for patients too elderly or high risk that they’ve suffered a stroke, or have lung disease. to undergo open heart surgery. The device, the In the past, physicians have relied on a balloon Basic Science Research Medtronic CoreValve® Transcatheter Aortic Valve procedure to open the heart valve, but this has Prosthesis, treats severe aortic stenosis with a proven to be a temporary fix, with results lasting Scientists pursue basic research catheter-based technology that does not require up to nine months before the symptoms return. questions in the laboratory to understand an incision in the chest or the use of a heart Dr. Sharma says the balloon procedure can be the fundamental mechanisms of lung machine. performed only a few times before it actually molecular, cell, and systems biology. begins to weaken the patient’s heart valve. David H. Adams, MD, Marie-Josée and Henry R. Kravis Professor and Chair of the Department Implantation of the CoreValve, a self-expanding THE CENTER FOR DISCOVERY of Cardiothoracic Surgery; Samin K. Sharma, stent measuring slightly more three centimeters, AND INNOVATION (CDI) MD, the Zena and Michael A. Wiener Professor is guided over a wire and a catheter placed in translational science and Director of the Cardiac Catheterization a peripheral artery through the diseased aortic Scientists use animal models and human Laboratory; and Annapoorna S. Kini, MD, valve, and once it expands in this position, the patients to explore disease mechanics. Associate Professor and Associate Director of new aortic valve begins functioning immediately. the Cardiac Catheterization Laboratory, have begun using the CoreValve discovery of potential System as part of the FDA’s novel therapeutics Pivotal Clinical trial. Dr. Scientists collaborate with research Adams is the trial’s national staff in ETI core facilities to develop Co-Principal Investigator. new molecules with the goal of creating new therapies, including mAbs, small “We think more than 70 molecules, percent of patients receiving and biologics. Industry partnerships with the CoreValve will survive biotech and pharmaceutical more than two years,” says companies begin to form. Dr. Sharma, whose estimates Industry partners assist in are based on the 13,000 devices the final steps of therapy that have been implanted in discovery to determine safety patients throughout Europe since 2007. phase 1 and efficacy, and to incorporate fda safety therapy into medical practice. trials David H. Adams, MD (LEFT), and Researchers test new treatments for Samin K. Sharma, MD (RIGHT), with the CoreValve device. safety and, in some cases, efficacy in humans through standard FDA trials.

pivotal fda clinical trials Physician-scientists conduct large-scale, well-controlled efficacy trials in order to distinguished by service gain FDA approval. Department of Rehabilitation Medicine Anniversary, continued from page 1 medical practice is changed The new therapy becomes available to The department has become a world-renowned center of excellence providing comprehensive patients. Large-scale effectiveness trials rehabilitation for patients with spinal cord injury, brain injury, stroke, limb amputations, multiple traumas, and joint replacement surgery. It is the only federally designated Model System of Care are conducted in patients with more facility in New York State for spinal cord injury and traumatic brain injury (TBI). Among its many complicated diseases to guide medical research accomplishments is the development of an assessment tool for diagnosing subtle brain damage, practice. and an intervention to address impairment of executive function, such as goal-setting, problem-solving, and planning abilities in patients with traumatic brain injury. Thousands of patients have reclaimed their lives through care and support from Mount Sinai practitioners. Notable examples include ABC News Reporter Robert Woodruff, who in 2006 sustained TBI after being hit by a roadside bomb while on assignment in Iraq, and Dennis Byrd, a former New York Jets football player who broke his neck during a game in 1992, and now can walk on his own. 2 medical milestones research frontiers A New Alternative to Open Heart Surgery $17.2 Million Grant for Research New Discovery into the on Immune Modeling and Origins of Brain Cells

Experimentation Miriam Merad, MD, PhD, Associate Professor of Gene and Cell Medicine at Mount Sinai School of Medicine recently received a five-year, $17.2 Mount Sinai School of Medicine, and her million grant from the National Institute of Allergy and Infectious team of researchers at The Mount Sinai Diseases, part of the National Institutes of Health (NIH), to improve Medical Center have made a significant the collection and computation of data used to study immunology and discovery that microglia, the small, infectious diseases. immune cells that reside in the central nervous system, have a unique origin, This is the second round of funding and are formed shortly after conception. that MSSM’s Program for Research on Microglia had been thought to develop Immune Modeling and Experimentation at birth, and originate at the same time (PRIME) has received since 2005, when the as macrophages, the body’s other immune program—directed by Stuart C. Sealfon, cells. The findings were published in MD, Glickenhaus Professor and Chair of the Miriam Merad, MD, PhD Science in November. Department of Neurology—was awarded $16.8 million. The study resolves a longstanding controversy about the origin of microglia cells, and has the potential to lead to new treatments for diseases of the “We are trying to change the paradigm of Stuart C. Sealfon, MD nervous system. Microglia protect vulnerable brain tissue from infection how research is done, especially research in and metabolic injury. They clear out debris and dead cells, reducing immunology and infectious diseases,” says Dr. Sealfon. “Our goal is to inflammation when infectious agents enter the brain. “They are very combine large amounts of information from different sources to reach important in maintaining brain integrity, which may be why they develop conclusions and accelerate the discovery process.” so early,” says Dr. Merad. Integrating mathematical approaches into research that ultimately has Studies suggest that defective microglia that increase with age may lead to an impact on patient care is particularly vital in the complicated realm the release of inflammatory substances that contribute to the development of infectious disease, according to Dr. Sealfon. of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, and PRIME will conduct large-scale experiments as a way to validate autoimmune disorders, such as multiple sclerosis. mathematical models and test their predictions. The PRIME team “Now that we know that microglia originate in early embryos, we should, includes colleagues at Yale University, Princeton University, Ohio in theory, be able to generate microglia from embryonic stem cells and inject State University, The BioAnalytics Group, LLC, a New Jersey-based them into a degenerated brain,” says Dr. Merad. “This study shows why it data analysis and management company, and Contur AB, a Swedish is so important to be able to conduct research with embryonic stem cells.” research software company. Dr. Sealfon says the NIH funding is an outgrowth of U.S. government concerns over managing the potential Translating these discoveries into clinically relevant treatments for threat of bioterrorism. neurodegenerative diseases will be the next phase of research.

young pioneers Benjamin R. tenOever, PhD, Receives Award

Benjamin R. tenOever, PhD, on Antimicrobial Agents and were the first to demonstrate that a of our choice,” he says. Assistant Professor of Microbiology, Chemotherapy (ICAAC) Young subset of viruses can be designed to distinguished by service A 2008 Pew Scholar, Dr. tenOever Mount Sinai School of Medicine, Investigator Award for his work in produce custom-made small RNAs,” has also received the Presidental was recently honored with the understanding small RNAs and their says Dr. tenOever. Early Career in Science Award, the American Society for Microbiology’s potential antiviral roles. At the most basic level, Dr. highest honor given by the United 2010 Interscience Conference Dr. tenOever’s research focuses on tenOever’s work centers on RNAs States government to outstanding two unique aspects of small RNAs, that are only 20 nucleotides in scientists and engineers who are called microRNAs, that exist in all length, which are naturally present beginning their careers. His the cells of the body. One aspect in cells, but can also be synthesized research has been published in of his research is based on the idea and artificially introduced. “In a more than a dozen journals, of utilizing these microRNAs in an nutshell, we can generate a novel including Cell, Science and antiviral capacity to generate novel vaccine by exploiting the cell’s Nature Biotechnology. The Young strategies for vaccine design. The microRNA profile, or take a very Investigator Award recognizes an second focus is based on engineering harmless virus and engineering it so early-career scientist for research recombinant viruses that can be that it now encodes small RNAs that excellence in microbiology and Benjamin R. tenOever, PhD used for therapeutic purposes. “We will essentially attack another virus infectious diseases. 3 new faces Michael J. Goldstein, MD, FACS

Michael J. Goldstein, rejection through the use of advanced and the number of organs available for transplant MD, FACS, a immunosuppressant drug regimens. He also in the Greater New York area. He is also the Vice renowned transplant performs procedures that maximize the use Chair of the United Network for Organ Sharing’s surgeon, who of organs that might otherwise have been less Organ Availability Committee, and is on the specializes in high- than optimal for transplantation. Medical Directors Council of the Association risk procedures that of Organ Procurement Organizations. Dr. Goldstein’s innovative technique for improve patient access minimally invasive kidney transplantation Dr. Goldstein serves as a medical advisor to Michael J. Goldstein, MD to transplantation, utilizes a small, two-inch incision, which the National Kidney Foundation of Greater has been appointed minimizes pain, accelerates patient recovery, New York and to pharmaceutical and bio- Associate Professor of Surgery and Director of and reduces hospital stay. technical companies. Kidney and Pancreas Transplantation at The Mount Sinai Medical Center. In addition to his work at Mount Sinai, Prior to joining Mount Sinai, Dr. Goldstein was Dr. Goldstein is Medical Director of the New an Assistant Attending Surgeon and an Assistant One of Dr. Goldstein’s areas of expertise is York Organ Donor Network, a nonprofit Professor at New York Presbyterian Hospital, operating on patients with high immunologic organization that works to improve the quality Columbia University Medical Center. risk, and helping them to overcome organ

Robert Maki, MD, PhD

Robert Maki, MD, PhD, a leading sarcoma Medical Oncology, and in the Department of Orthopaedics, he will cancer researcher, has joined The Mount deliver personalized treatments to sarcoma patients, and develop novel Sinai Medical Center as the Chief of Pediatric therapeutics in this population. This collaboration will offer comprehensive Hematology/Oncology Division, and Medical specialty care to adult and pediatric patients with sarcoma, and build a Director of the Sarcoma Cancer Program at The portfolio of translational clinical trials to improve the outcome of patients Tisch Cancer Institute. with this aggressive cancer.

Robert Maki, MD, PhD Dr. Maki is credited with making significant Dr. Maki will help expand the breadth of the pediatric clinical program contributions to the understanding and targeting in Hematology/Oncology, focusing on soft-tissue and bone sarcomas, of soft-tissue and bone sarcomas, of which there are more than 50 types. adolescent cancer care, and transitioning pediatric cancer patients to His expertise in novel therapies for treatment has led him to investigate adult care. new drugs to attack molecular targets. Prior to joining Mount Sinai, Dr. Maki was an Associate Professor of At The Tisch Cancer Institute, Dr. Maki’s responsibilities include the Medicine at the Weill Cornell Medical College, and Co-Director of the expansion of basic and translational sarcoma cancer research programs. Adult Sarcoma Program at Memorial Sloan-Kettering Cancer Center. Working closely with his colleagues in the Division of Hematology and

Kenneth Rosenzweig, MD

Kenneth Rosenzweig, A groundbreaking researcher in radiation therapy, less invasive surgery to give patients with MD, a respected Dr. Rosenzweig was the principal investigator for lung cancer higher cure rates and faster physician-scientist a critical-dose escalation study that established recovery times. who specializes in the maximum tolerated dose of radiation that can An accomplished educator, Dr. Rosenzweig was the treatment of lung be safely delivered. He has published more than named “Teacher of the Year” by the Association cancer and malignant 70 articles in scientific journals, and has authored of Residents in Radiation Oncology. He has mesothelioma, has numerous textbook chapters, including one in served as a consultant to the International been appointed Chair Principles and Practice of Oncology, the leading Atomic Energy Association, and on many of the Department of textbook of cancer medicine. professional committees, including the Radiation Kenneth Rosenzweig, MD Radiation Oncology In his new position, Dr. Rosenzweig will Therapy Oncology Group (RTOG) Lung at Mount Sinai School continue the innovative research in radiation Committee, the RTOG Data Monitoring of Medicine. Dr. Rosenzweig has developed oncology that engaged him at Memorial Sloan- Committee, and the National Cancer Institute innovative methods for delivering precise doses Kettering Cancer Center, where he worked as Clinical Trials Evaluation Panel. of radiation to lung tumors during key points in a radiation oncologist from 1997 to 2010. He the respiration cycle. His work enables physicians Dr. Rosenzweig completed his residency at will be part of a multidisciplinary team of top to safely increase the radiation dose, shorten the Joint Center for Radiation Therapy at surgeons, radiologists, and researchers at treatment, spare healthy tissue, and improve the Harvard Medical School. Mount Sinai who are using earlier diagnoses and outcome in people receiving radiation.

4 philanthropy Zweigs Pledge $5 Million to Center for Living Donation

Barbara and Martin Zweig, PhD, recently committed to a $5 million leadership gift to the Recanati/Miller Transplant Institute (RMTI) to support an ambitious new center and establish an endowed professorship.

The center will be named the Zweig Family Center for Living Donation in their honor, and will focus on providing the best in medical, surgical, and psychological care to living kidney and liver donors. The Sidney J. Zweig Professor of Medicine will play a key role in advancing the knowledge and practice of transplantation.

“Living organ donors are giving the most a person can give. The Zweig Family Center for Living Donation will honor that gift by providing exceptional care.” — MARTIN ZWEIG, PhD

“This gift will allow us to provide dedicated care and specialized services for Martin Zweig, PhD, and Barbara Zweig these incredible people who actually give a piece of their own liver or one of their own kidneys to save another person’s life,” says Sander Florman, “Living organ donors are giving the most a person can give,” says MD, the Alfred and Florence Gross Professor of Surgery and Director of the Dr. Zweig. “The Zweig Family Center for Living Donation will Recanati/Miller Transplant Institute. Currently, there is a critical shortage honor that gift by providing exceptional care. Barbara and I are happy of organs, both nationally and within the New York region. to be a part of this important, innovative new center.”

patient-centered care A Focus on Living Donors

The recently named Zweig Family him or her about the risks and psychological support, and transplantation experts, including Center for Living Donation at the benefits of donation. During the monitoring for complications. In Marcelo Facciuto, MD, and Juan Recanati/Miller Transplantation inpatient and recovery phase, the post-recovery, patients are taught Pablo Rocca, MD. Dr. Facciuto, Institute (RMTI), is the first major staff focuses on safety, advocacy, how to maintain their health and who was named Surgical Director of multi-organ program in the nation receive long-term monitoring. Living Donor Liver Transplantation, to address the unique physical and has broad surgical experience Dianne LaPointe Rudow, DNP, a psychological concerns of living with end-stage liver disease and leading advocate for living donors, donors. Emphasis is placed on hepatocellular carcinoma. Dr. is the center’s director. She helped meeting each patient’s unique pre-, Rocca, the Associate Director of develop national and New York peri-, and post-transplant needs fellowship training at Mount Sinai, State standards for donor care while by providing a wide range serves as Surgical Director of Living serving on the board of directors of treatments and services Donor Kidney Transplantation. of the Organ Procurement and throughout the transplant process, The center has dedicated resources Transplantation Network/United including counseling, support to ensure that donor safety is Network for Organ Sharing groups, yoga, nutrition counseling, paramount. The gift from the (UNOS), and at the New York and patient education on donation Zweig family will also include the Center for Liver Transplantation. and overall health. renovation of four patient hospital In addition to Dr. LaPointe Rudow rooms specifically for the care Pre-donation care is focused on there is a multidisciplinary team of of donors. evaluating the donor and educating Dianne LaPointe Rudow, DNP

5 photo essay Prostate Cancer Imaging

B

A C

Whole-body Philips MR/PET images show a 69-year-old man with prostate cancer and persistent hypermetabolism in (A): the left lateral resection area; and (B): near the base of the penile bulb. (C) This image appears to show the recurrence of a suspicious looking tumor.

To learn more, visit www.mountsinai.org/tmii

PHOTO: Zahi A. Fayad, PhD, is Director of the Translational and Molecular Imaging Institute; Professor of Radiology and Medicine (Cardiology); Director and Founder, the Eva and Morris Feld Imaging Science Laboratories; and Director, Cardiovascular Imaging Research.

6 COMMENTARY A National Call to Action: Reduce Barriers to Mental Health Care

Numerous studies show that the availability of primary care physicians correlates with better health outcomes and lower health care costs. It is also well documented that in the United States, the supply of primary care physicians is far below that of nations with better health care outcomes and lower costs.

In the aftermath of the Tucson, Arizona, be allowed to magnify negative attitudes toward shootings, much has been said about the mental illness. role mental illness might have played in this It is unfortunate that at this critical juncture, tragedy. Such discourse is understandable, the gap between the need for mental health but unfortunately it has tended to reinforce, services and resources to fund them is large and rather than challenge, misconceptions about growing. As local and state governments struggle mental illness. to balance budgets, mental health services are often first on the chopping block. One result of this reduction is the expanding number of people “Given the prevalence and burden with mental illnesses who are incarcerated, rather Wayne Goodman, MD of mental illness, funding is both than in treatment programs, for predominantly inadequate and disproportionately nonviolent crimes—situations that might have been prevented by better psychiatric management low compared to that for heart in the first place. disease, stroke, and cancer.” Given the prevalence and burden of mental — Wayne Goodman, MD and illness, funding is both inadequate and Dennis S. Charney, MD disproportionately low compared to that for heart disease, stroke, and cancer. If this trend is not reversed, even those who do seek help may not be able to find or afford it—and those who One is that mental illness leads inexorably to would benefit from outreach may never violence. Outwardly directed violence is rare be identified and treated. The Mental Health among the majority of people with a mental Parity and Addiction Equity Act, which lifted illness. In fact, individuals with a mental some restrictions and guaranteed coverage in disorder are much more likely to harm certain circumstances, is a step in the right themselves or be victims of violence. In only a direction, but there are loopholes that will still small minority, such as those with an unstable leave many uninsured. psychotic disorder that is accompanied by paranoia and “command” auditory Increased funding directed at research into risk Dennis S. Charney, MD hallucinations, is violent behavior elevated. factors—both behavioral and genetic—would also help us develop the tools that could detect Unwittingly, the media may be perpetuating mental illness early and accurately. As with other another myth: that people with mental illness medical diseases, early intervention may change appear abnormal. The demonic smirk and the trajectory of mental illness. haunting countenance of the alleged shooter are ubiquitous and, for many, may become the What happened in Tucson exposed fault lines in archetypal face of severe mental illness. However, our mental health care system, but we must not mental illness is faceless—invisible, yet pervasive. let it lead to mixed or erroneous messages about It does not discriminate by gender, race, or mental illness. Instead we must use it as a call to socioeconomic status. In the vast majority of action to strengthen our mental health system. cases, it is no more recognizable on the surface than diabetes.

Finally, the spotlight on Tucson could deepen the To learn more, visit www.mountsinai.org/Commentaries. already profound stigma associated with mental Wayne K. Goodman, MD, is Professor and Chair of the illness. Negative attitudes are felt by those with Department of Psychiatry at The Mount Sinai Medical mental illness, their families, and the public alike. Center, and Dennis S. Charney, MD, is Dean of Mount Stigma makes people more reluctant to seek help, Sinai School of Medicine. This commentary was first or to offer it. The events in Tucson should not published in The New York Times on February 22, 2011.

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