Engaging Basic Scientists in Translational Research Identifying Opportunities, Overcoming Obstacles
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FASEB Report Layout.FINAL.indd Spread 1 of 28 - Pages(i) 3/20/12 5:19 PM STEERING COMMITTEE Richard Galbraith, MD, PhD, Chair, FASEB Mariana Morris, PhD, Assistant Vice President for Translational Research Steering Committee; Associate Graduate Studies, Wright State University; Professor and Dean, Patient Oriented Research, The University of Chair, Department of Pharmacology and Toxicology, Vermont College of Medicine Boonshoft School of Medicine, Wright State University Richard Bockman, MD, PhD, Professor of Medicine, Sharma Prabhakar, MD, Professor and Chief, Division Weill Cornell Medical College, Hospital for Special of Nephrology and Hypertension; Vice Chairman, Surgery, Cornell University Department of Medicine, Texas Tech University Health Sciences Center Stanley Cohen, MD, Professor and Chair, Department of Pathology and Laboratory Medicine, New Jersey Usha Raj, MD, Professor and Head, Department of Medical Center, University of Medicine and Dentistry of Pediatrics, University of Illinois at Chicago New Jersey Peter Rubenstein, PhD, Professor of Biochemistry, Paul Dechow, PhD, Professor and Vice Chair, University of Iowa Department of Biomedical Sciences, Baylor College of John A. Smith, MD, PhD, MMM, DSc (Hon), Professor Dentistry, Texas A&M Health Science Center of Pathology and Director, Division of Laboratory Charis Eng, MD, PhD, FACP, Sondra J. and Stephen R. Medicine, University of Alabama at Birmingham Hardis Endowed Chair of Cancer Genomic Medicine; Patrick Stover, PhD, Professor and Director, Division of Chair and Director, Genomic Medicine Institute; Nutritional Sciences, Cornell University Director, Center for Personalized Genetic Healthcare; American Cancer Society Clinical Research Professor, Nancy S. Sung, PhD, Senior Program Offi cer, Cleveland Clinic Lerner Research Institute Burroughs Wellcome Fund William Galey, PhD, Director, Graduate and Medical William Talman, MD, Professor of Neurology and Education Programs, Howard Hughes Medical Institute Neuroscience; Chief, VAMC Neurology Service; Director, Laboratory of Neurobiology, Department of Neurology, Roy and Lucille Carver College of Medicine, University of Iowa
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COVER IMAGE CREDITS (clockwise from top) Laboratory animal research (Getty Images); patient undergoing medical examination (Getty Images); patient being vaccinated (Centers for Disease Control and Prevention/James Gathany); electron micrograph of Mycobacterium tuberculosis (National Institute of Allergy and Infectious Diseases); immunofl uorescent image of protein in cells (National Human Genome Research Institute/Antonio Velayos-Baeza); samples prepared for high-throughput assays (Sandia National Laboratories/Randy Wong)
FASEB Report Layout.FINAL.indd Spread 2 of 28 - Pages(ii) 3/20/12 5:19 PM Organization Weblink Description Preface TRANSLATIONAL RESEARCH FUNDING National Institute http://nih.gov/ Provides translational research support for basic investigators Basic scientists play a key role in improving human health and treating disease. of Health through investigator-initiated and targeted grants programs for individuals and institutions, as well as opportunities to access Yet despite widespread national interest in accelerating the pace at which resources, instrumentation, and core facilities. Specifi c programs new and improved medical interventions are developed, few initiatives aimed at facilitating translational science are described in the main have focused specifi cally on engaging basic investigators in this process text (Box A). of translation. The Federation of American Societies for Experimental U.S. Department of http://www.research.va.gov/ Provides translational research support for basic and clinical Biology (FASEB), an organization of more than 100,000 researchers— Veterans Affairs VA investigators through investigator-initiated merit review most of whom are basic scientists—seemed to be an excellent place awards and targeted announcements. Investigators can also access translational research resources such as the Clinical to start to address translational research from the vantage point of basic Research Pharmacy and Pharmacogenomics Analysis Laboratory. investigators trained to conduct fundamental biological research. To further Additionally, the VA supports several relevant career development this goal, FASEB held a symposium in March 2011 titled “Engaging Basic programs, including the Career Development Enhancement Award, which provides support for educational leave to learn new research Scientists in Translational Research: Identifying Opportunities, Overcoming skills. Richard Galbraith, Obstacles” to discuss and formulate a set of recommendations for increasing the MD, PhD, Department of http://www.defense.gov/ Provides translational research support to intramural and participation of these investigators in translational science. Defense http://www.darpa.mil/ extramural basic investigators. Extramural programs include the The University of The symposium was sponsored by the Burroughs Wellcome Fund, the U.S. Vermont College of http://cdmrp.army.mil/ Congressionally Directed Medical Research Programs, Defense Department of Veterans Affairs, the Doris Duke Charitable Foundation, the http://dmrdp.fhpr.osd.mil Advanced Research Projects Agency, and the Defense Medical Medicine Research and Development Program. Howard Hughes Medical Institute, and Merck Sharp & Dohme Corp. It attracted approximately 150 people, including representatives from the fi ve sponsoring Nongovernmental, http://www.healthra.org/ Provides grant funding for translational researchers and research Not-for-profi t teams. Many, but not all, of these programs are targeted at specifi c organizations; National Institutes of Health leadership; scientifi c publishers; and organizations diseases, conditions, or biological systems. The Health Research research trainees, junior and senior faculty, department chairs, deans, chancellors, Alliance (see link) is a consortium of 50 such organizations, some and presidents from numerous, diverse academic research institutions. In a mix of which have translational research funding opportunities for basic of lectures, panel presentations, and facilitated group discussions, participants scientists. examined the benefi ts of engaging basic scientists in translational research, the unique challenges these investigators face in carrying out translational research projects, and the ways that the research community could collectively help them to overcome these challenges. In these proceedings, we have attempted to distill the major points emerging from those conversations and to offer a realistic set of recommendations aimed at individual scientists, funding agencies, professional societies, scientifi c publishers, and academic institutions. We hope that this report will inspire and accelerate the critical involvement of basic scientists in translating the fruits of their labor to benefiefi t society.sos cietyy.
Richardhard GaGalbraith,lbraitth MMD,D PPhDhDD Chair, FASEB Translational Research Steering Committee Associate Dean, Patient Oriented Research The University of Vermont College of Medicine
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TRANSLATIONAL RESEARCH TRAINING (continued) Basic scientists play a key role in generating the research discoveries that TRIUMPH University of Texas (UT) Provides training in clinical and translational Educate and are translated into applications that improve human health. A number (Translational Graduate School of Biomedical research to postdoctoral researchers through train postdoctoral of obstacles—scientifi c, institutional, cultural, and policy—limit Research in Sciences, MD Anderson Cancer didactic course work, clinical rotations, researchers opportunities for basic scientists to conduct translational science and Multi-Disciplinary Center, UT Medical School and mentorship. The long-term goal is to produce translational scientists who can be may slow the pace at which discoveries are translated into clinical Program) http://tinyurl.com/3fprqhk Postdoctoral teamed with suitable physician scientists in applications. Researchers trained in basic science may face inadequate Fellowship translational research laboratories. funding, resources, or infrastructure for developing translational research programs; insuffi cient experience with essential methods and techniques; RECOGNIZING AND REWARDING TRANSLATIONAL RESEARCH complex regulatory requirements; or suboptimal recognition or reward for Team Science American Association for Cancer Recognizes an outstanding interdisciplinary Recognize team pursuing applied research that may stretch beyond the boundaries of their Award Research research team for innovative and meritorious scientists http://tinyurl.com/38ha78b science that has or will likely advance department and discipline. These challenges can limit professional interest fundamental knowledge of cancer or that in translating research discoveries and hamper the enterprise at a time when it has applied existing knowledge to advance the detection, diagnosis, prevention, or should be expanding to capitalize on the explosion of basic science knowledge. treatment of cancer. Teams are composed In March 2011, the Federation of American Societies for Experimental of independent faculty researchers with Biology (FASEB) organized a symposium to address issues important to basic complementary interdisciplinary expertise, each of whom has made separate scientists choosing to conduct translational research. Attendees examined substantive and quantifi able contributions to the contributions that basic scientists have made and can make in this area, the research. the benefi ts that investigators and institutions derive from participating in Tenure Track Offer National Institutes of Health Provides guidelines for writing letters of Provide guidance translational science, and the unique challenges that basic investigators face in Letter Template: http://tinyurl.com/c38kmu9 offer to, and reviewing and rewarding, on appointing Team and interdisciplinary scientists. It includes interdisciplinary, developing translational research programs. Participants also addressed strategies Interdisciplinary a set of questions to help identify the collaborative to facilitate the involvement of basic scientists in translational research. Science roles, responsibilities, and expectations of researchers scientists and their departments. Benefi ts to Engaging Basic Scientists in Translational Research University of University of California Provides a model for how academic Provide guidance departments and committees can weigh A number of speakers described how basic scientists can benefi t personally Southern California http://tinyurl.com/c2gehxb on rewarding Tenure and interdisciplinary research and collaborative interdisciplinary, and professionally by participating in translational research. They detailed the Promotion Manual scholarship when making tenure and collaborative satisfaction and inspiration that come from working to translate discoveries into promotion decisions. research
treatments and diagnostics for human diseases. Importantly, their involvement GENERAL RESOURCES in clinical applications led to deeper insights into the biological mechanisms they were investigating, led to novel research ideas, enabled them to bring new CTSA Consortium’s CTSA Consortium Provides links to information for basic, Identify research Resources for http://tinyurl.com/6peeoab clinical, and translational research resources research methods into their laboratories, and improved the opportunity to Researchers communities, including research networks, publish. Senior research leaders attending the meeting suggested that biomedical research tools, and funding opportunities available through public and private research institutions also benefi t, because translational research advances their institutions. core mission to enhance human health and well-being, enhances research Team Science National Cancer Institute (NIH) Provides a user-generated collection of Identify research collaboration among their faculty, and helps forge partnerships with industry, Toolkit https://www.teamsciencetoolkit. information and resources that support resources garner additional research funding, and attract trainees. cancer.gov the practice and study of team science. It connects professionals from many disciplines and provides a forum for sharing knowledge and tools.
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FASEB Report Layout.FINAL.indd Spread 4 of 28 - Pages(iv, 47) 3/20/12 5:19 PM research funding programs and policies. Those Resource, Policy, Organization Challenges to Engaging Basic or Program (weblink) Description Purpose Scientists in Translational Research proposals were shaped by the symposium steering committee into a set of practical TRANSLATIONAL RESEARCH TRAINING (continued) Despite its benefi ts, initiating and sustaining recommendations aimed at the major a translational research program can be stakeholders and are summarized below. National CTSA University of Rochester Makes available a variety of clinical and Educate and train challenging. Speakers noted that basic Educational http://tinyurl.com/cqkgyhc translational educational modules from students and scientists tend to lack training in human It is recommended that research institutions Resource Program the CTSA consortium training programs investigators at all encourage and engineer a cultural shift and the NIH Institutes and Centers. The levels disease processes and translational research toward greater collaboration, cooperation, modules are specialized educational courses approaches. Furthermore, the physical and intended for audiences from K-12 students communication, and respect among basic and cultural separation of basic and clinical to experienced faculty and include a mix of clinical scientists by: departments at research universities often limits materials for web- and classroom-based 1. Providing didactic and experiential learning learning. opportunities for basic scientists to interact opportunities that place basic research with patients and to network with and learn Physiology The American Physiological Highlights translational research Educate graduate in the context of pathophysiology and InFocus: Society programming at the society’s annual meeting students, from clinicians and clinical researchers who pathobiology and by providing opportunities Physiology in http://tinyurl.com/7xopj9x; through designated sessions and meeting postdoctoral have skills that complement their own. Basic Medicine/ http://tinyurl.com/6wx2opr tracks. researchers, and to acquire training in the wide range of skills Translational independent scientists also may fi nd it diffi cult to obtain needed to conduct translational research. funding for translational work and to navigate Physiology Track investigators 2. Using multiple approaches to increase The Seminars University of Texas at Seminar series that brings together Promote education the maze of administrative and regulatory issues the interdisciplinary interactions among in Translational San Antonio investigators from basic, clinical, and social and collaboration involved. Those who do succeed may fi nd it academic and industry scientists and Research (STRECH) http://translationalseminars. sciences from multiple university campuses. diffi cult to publish their work in journals that trainees. utsa.edu/ Seminars highlight the translation of tend to favor hypothesis-driven research over research discoveries from bench to bedside 3. Revising tenure and promotion policies to community and promote the formation of goal-directed or applied science. Likewise, basic to recognize—not punish—creative and multidisciplinary clinical and translational science departments and tenure and promotion nontraditional risk-taking to advance research teams. committees may not attribute the same value translational science. Translational American Association for Provided an intensive week-long introduction Educate graduate to translational research as they would to basic 4. Connecting basic investigators to the Cancer Research Cancer Research to translational cancer research for basic students, research in the tenure and promotions processes. for Basic Scientists http://tinyurl.com/4xhtcsy scientists transitioning to translational postdoctoral infrastructure, equipment, and technical research. The goals were to provide researchers, and and administrative support necessary to participants a better understanding of independent Facilitating the Participation of Basic move their discoveries from the bench to translational research, teach them how to investigators Scientists in Translational Research the bedside. adapt their research for maximum clinical Translational research opportunities can be impact, and help them transition into a new It is recommended that funding agencies career in translational cancer medicine. facilitated through coordinated action by continue to support basic research to ensure Translational American Federation for Annual researcher-initiated and peer- Educate graduate research institutions, funders, professional a deep and broad reservoir of new knowledge Medical Research Medical Research reviewed seminar series showcasing bench- students, societies, scientifi c publishers, and basic upon which translational and clinical science Symposia Series http://www.afmr.org/eb2011.cgi to-bedside research addressing cutting postdoctoral investigators themselves. Conference participants can grow, and: and Workshop edge, clinically important topics. AFMR also researchers, and were asked to propose recommendations in four conducts a workshop to provide investigators independent 1. Provide specifi c funding for investigator- with perspectives and practical tools for investigators key areas: 1) helping basic scientists to acquire initiated translational research grants developing successful clinical-translational translational research training; 2) providing in addition to support for translational medical research programs. Workshops appropriate recognition and rewards for infrastructure and resources. topics have included drug development, the contributions basic scientists make to intellectual property, connecting research 2. Ensure that grant application review panels cultures, and managing confl ict of interest. translational research; 3) forging collaborations have the appropriate expertise to review among basic and clinical scientists in academe translational research projects rigorously and industry; and 4) optimizing translational and fairly.
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FFASEBASEB RReporteport Layout.FINAL.inddLayout.FINAL.indd SpreadSpread 5 ofof 2828 - Pages(46,Pages(46, v)v) 33/20/12/20/12 55:19:19 PMPM 3. Use their convening power to facilitate It is recommended that individual scientists Resource, Policy, Organization interaction and collaboration among basic who are open to the translational implications or Program (weblink) Description Purpose and clinical scientists in academe and of their work: industry. 1. Learn to defi ne a health need with the same TRANSLATIONAL RESEARCH TRAINING (continued) 4. Fund high school, college, graduate, and precision as a basic science hypothesis. Demystifying National Institutes of Health A weekly, one-hour course for PhDs that Educate graduate postdoctoral translational educational Medicine http://demystifyingmedicine. includes presentation of patients, pathology, students, 2. Seek mentors and collaborators from od.nih.gov/ diagnosis, and therapy in the context postdoctoral research programs and mentorship by basic, different disciplines. of major disease problems and current researchers, and translational, and clinical scientists. 3. Seek funding to work in the translational research. The course is designed to help independent bridge the gap between advances in biology investigators 5. Work together to evaluate the outcomes of space. and their application to major human efforts to promote translational research. 4. Be aware of promotion and tenure diseases. Each session includes clinical and basic science components presented by staff It is recommended that professional expectations and take responsibility for and outside invitees. societies: defi ning the intellectual areas for which Lucille P. Markey Washington University in St. Two-year course of study for graduate Educate and train 1. Spark interest in translational research by they will be recognized as leaders. Special Emphasis Louis students and postdoctorates that PhD students raising its profi le in featured symposia, It should be emphasized that it is not the Pathway in Human http://dbbs.wustl.edu/ supplements biomedical PhD education. It and postdoctoral workshops, and sessions at professional Pathobiology markeypathway includes a course in Pathobiology of Human researchers goal of FASEB or this initiative to convert basic Program Disease States, individualized clinical meetings. scientists into clinical researchers. Rather, the mentorship, and an annual retreat enabling 2. Provide resources and opportunities to goal is to foster the creation of an environment personal and scientifi c interactions between trainees and faculty. facilitate interactions among basic and that encourages basic biomedical researchers to clinical researchers. consider the translational potential of their work Masters of Science Stanford University Provides PhD students with exposure to Provide masters in Medicine Degree http://msm.stanford.edu/ medicine to foster translational research. level medical 3. Recognize the contributions basic scientists and ensure that there are opportunities to apply Program Students are required to complete PhD concept training for make in translation by providing awards or modern biological knowledge and expertise to course requirements and lab rotations. PhD students improving human health and treating disease. During the fi rst two years of the master’s other forms of recognition for translational, program, they participate in basic biomedical team, or interdisciplinary science. science courses alongside the university’s 4. Advocate for policy and programmatic medical students and take a seminar dedicated to issues in translational medicine. changes that would facilitate the In the second year, they choose thesis labs participation of basic investigators in and clinical mentors. translational research. MD-PhD Resources Association of American Medical Provides links to resources related to MD/ Provide information It is recommended that publishers: Colleges PhD training, including MD-PhD training about MD-PhD http://tinyurl.com/6wwa9eh programs in the United States and Canada training 1. Ensure that the role of individual authors is and workshops and research programs for clearly articulated in publications. students interested in pursuing combined MD-PhD training. 2. Encourage editors to identify and highlight Med into Grad Howard Hughes Medical Supports and encourages graduate schools Integrate medical the contributions that basic research Initiative Institute to integrate medical knowledge into their knowledge into PhD fi ndings could make to medicine and/or http://tinyurl.com/7n7szu3 PhD training. The program’s goal is to training public health. produce researchers who will recognize which biological problems are of the greatest 3. Prioritize the publication of papers that clinical relevance, have the knowledge and combine the study of clinical outcomes with skills necessary to facilitate the translation mechanistic considerations. of new biological knowledge into tools to improve human health, and be able to create fruitful research partnerships with physicians.
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IDENTIFYING RESEARCH TOOLS AND RESOURCES Basic scientists are the foundation of the biomedical research enterprise. CTSA Multiple Facilitates matches between CTSA-affi liated Identify research Their work is key to understanding fundamental biological processes and Pharmaceutical http://www.ctsapharmaportal. investigators and the pharmaceutical compounds, Assets Portal org/aboutus.html industry to develop research partnerships expertise, and mechanisms of disease pathogenesis, and it has been critical to preventing, based on potentially valuable compounds collaborators diagnosing, and treating diseases and conditions that affl ict millions of that did not make it to the market. Academic people. Yet despite major advances in fundamental biology, there is researchers can submit proposals to pharma partners requesting a specifi c drugs or a widespread concern about the slow pace at which these discoveries are drug category with a desired effect. Pharma translated into safe and effective clinical interventions. The National partners can contact target experts identifi ed Institutes of Health (NIH) estimates that 80 percent to 90 percent of from clusters of researchers organized potential therapeutics in preclinical testing run into problems that preclude around areas of expertise. them from advancing to the clinical trial phase.1 Numerous initiatives to eagle-i Multiple; consortium of nine Prototype of a national research resource Identify research member institutions discovery network to help biomedical resources speed translation are under way at the national and institutional levels, many of https://www.eagle-i.net/ scientists search for and fi nd previously John A. Smith, MD, which have been aimed at providing clinical scientists with the knowledge and unknown, but highly valuable, resources. PhD, MMM, DSc tools needed to translate research discoveries into improved patient care. Less Resources accessible through the site (Hon), University attention, however, has been given to the contributions that basic scientists make include animal models, reagents, cell and tissue banks, core facilities, and training of Alabama at to the process of translational research. opportunities. Birmingham A somewhat fl uid and amorphous concept, translational research is the term used to describe a spectrum of scientifi c investigation aimed at: 1) transferring TRANSLATIONAL RESEARCH TRAINING laboratory discoveries about disease mechanisms into new methods for diagnosing, COALESCE Northwestern University Aims to create, evaluate, and disseminate Educate and preventing, and treating disease and testing these methods in humans; 2) taking online learning resources to enhance Clinical and Translational train researchers results from clinical studies into clinical practice and understanding the effi cacy Science Center skills needed to perform transdisciplinary, and institutional http://teamscience.net team-based translational research. Learning development offi cers and dissemination of health care interventions; and 3) using the knowledge modules help users acquire and apply in team research gained to improve health care policy. Scientists from many disciplines often knowledge of team science and provide an are involved in this work, ranging from the most basic investigators in the life, experiential learning environment where they can engage virtually in the challenges of chemical, physical, mathematical, engineering, and computer sciences to those team research. in the clinic. Research across the continuum does not always proceed linearly. Clinical and Northwestern University Provides a two-day program to educate Educate Often it is an iterative, bidirectional process in which insights into biological Translational http://tinyurl.com/bpwxaag medical students and undergraduates in undergraduate and mechanisms and disease processes inform and spur new clinical interventions Research Summer the skills required for biomedical research. medical students and, conversely, observations about the nature and progression of disease made in Seminar Series It covers topics including, biostatistics, epidemiology, responsible conduct of the course of patient care and clinical research stimulate new basic investigations. research, human subjects research, the This paper focuses on the former pathway. research enterprise, clinical trial conduct, Although individuals trained in basic science can contribute to research drug and device development, and career opportunities. at any point along this spectrum, their expertise is especially valuable during the fi rst, or “T1,” stage. This is where an understanding of human biology, Core Competencies CTSA Consortium A set of competencies within 14 thematic Educate graduate for Clinical and http://tinyurl.com/cyoxukh areas that defi ne the skills, attributes, and students, pathogenesis, and basic science methods converge to bear on the identifi cation Translational knowledge needed to conduct clinical and postdoctoral and characterization of disease targets, assay development, lead identifi cation and Research translational research. The competencies researchers, and high-throughput screening, and preclinical evaluation of potentially therapeutic can serve as a guide for anyone considering independent developing a translational curriculum at investigators 1 multiple graduate levels. National Institutes of Health. 2009. “NIH Announces New Program to Develop Therapeutics for Rare and Neglected Diseases.” Accessed May 30, 2011, at www.nih.gov/news/health/may2009/nhgri-20.htm.
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ESTABLISHING COLLABORATIONS (continued) NIH Director Francis Collins, MD, PhD, opened the symposium with a presentation titled “Catalyzing Opportunities in Translational Research.” He emphasized NIH’s Harvard Harvard University Provides a research networking and Identify expertise, Catalyst Profi les http://tinyurl.com/7lkqyaj expertise mining software tool that connects collaborators continued support for basic science and the important contributions it makes to the people by combining basic directory translational research pipeline. Dr. Collins also provided an overview of NIH efforts to information with expertise keywords. Each promote and facilitate the movement of basic science discoveries into therapeutic person in the network has a profi le page that applications. Those efforts are described below. includes his or her name, titles, affi liations, and contact information. Enables the creation of automatically formed passive networks NIH-Supported Basic Research accounts for approximately 52 percent of its based on shared traits (e.g., publications, research portfolio. A good deal of this work is aimed at understanding the molecular departments) and active networks defi ned by basis of disease and identifying potential therapeutic targets. the user. Research Multiple, including Describes speed networking sessions that Identify expertise, The NIH Molecular Libraries program offers public-sector biomedical researchers access to the large-scale screening “Speed Dating” Cornell and Dalhousie aim to spark collaborations across disciplines collaborators capacity necessary to identify small molecules that can be optimized as chemical probes to study the functions of Universities and institutions. Participants (e.g., academic genes, cells, and biochemical pathways. The goal of this program is to lead to new ways to explore the functions of http://tinyurl.com/7h3b82o; investigators, industry scientists, physicians) are given two to three minutes to exchange genes and signaling pathways in health and disease. http://tinyurl.com/7fouycf cards, biographies, and research interests before moving on to share the same The Therapeutics for Rare and Neglected Diseases program encourages and speeds the development of new information with the next participant. drugs for rare and neglected diseases. This unique program creates a drug development pipeline within NIH and Research Team Northwestern University Offers collaboration enhancement for Provides support for is specifi cally intended to stimulate research collaborations with academic scientists, nonprofi t organizations, and Support and Clinical and Translational team-based, cross-disciplinary translational team science pharmaceutical and biotechnology companies working on rare and neglected illnesses. Development Sciences Institute biomedical research and helps translate http://tinyurl.com/6rxxsqh research fi ndings about team science into The Bridging Interventional Development Gaps program (formerly the Rapid Access to Interventional Development effective practices for teams and funders. [RAID] program) makes available, on a competitive basis, certain critical resources needed for the development of Resources include expert/collaborator identifi cation and referral, collaboration new therapeutic agents. Available services include the production, bulk supply, GMP manufacturing, formulation, and facilitation, team science tools and development of an assay suitable for pharmacokinetic testing and animal toxicology. Assistance also is provided with resources, collaborative research funding the regulatory process. information, collaborative research program development, and team science training. SciVal Experts SciVal Experts Provides a directory of research expertise Identify expertise, http://preview.tinyurl. prepopulated with publication histories from collaborators com/7pn9pd2 Elsevier’s Scopus database. It provides a visual analysis of relevant concepts that compounds in molecular, cellular, and animal opportunities, funding agencies such as NIH instantly exposes a researcher’s distinctive expertise. It also can incorporate institutional models. Recent research breakthroughs provide have instituted an array of translational research data and individual researcher updates. an ever-widening landscape of opportunities for programs (see Box A). VIVO Multiple; available to institutions Provides an open source semantic web Identify research, basic investigators to work in these areas. These However, a number of obstacles—scientifi c, with relevant technology application that enables the discovery of scholarship, and include the completion of the Human Genome institutional, cultural, and policy—have limited http://www.vivoweb.org/ research and scholarship across disciplines collaborators Project and dramatic advances in information the opportunities for basic investigators to and institutions by creating a semantic technology; biocomputing; high-throughput conduct translational science. This work cloud of information that can be searched and browsed. It is populated with detailed technologies for screening, identifying, and is best conducted through multi- and profi les of faculty and researchers including studying compounds of interest; and novel interdisciplinary collaborations, which can information on publications, teaching, imaging capabilities. Recognizing these be diffi cult to establish and maintain in service, and professional affi liations.
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FASEB Report Layout.FINAL.indd Spread 8 of 28 - Pages(2, 43) 3/20/12 5:19 PM Appendix 3: Resources to Facilitate Participation in Translational Research The NIH Clinical Center is the nation’s largest hospital devoted entirely to clinical research. It conducts and supports research into the pathogenesis of disease; fi rst-in-human clinical trials; the development of This appendix supplements the report recommendations by providing examples of policies, programs, state-of-the-art diagnostic, preventive, and therapeutic interventions; and clinical research training. and practices that could facilitate the engagement of basic scientists in translational research. It is not intended to be a comprehensive list. Rather, it aims to give a general “fl avor” of the types of The Clinical and Translational Science Award (CTSA) program creates a defi nable home for clinical and translational approaches institutions, including universities, funding organizations, and professional societies, may research at academic health centers across the nation. CTSA consortium institutions are building capabilities in want to adopt. connecting basic scientists with clinically experienced researchers to support training and to build a fully functional national network.
Resource, Policy, Organization The NIH-Food and Drug Administration Partnership spearheads collaborative work on important public health or Program (weblink) Description Purpose issues. The Joint Leadership Council works together to help ensure that regulatory considerations form an integral component of biomedical research planning and that the latest science is integrated into the regulatory review process. ESTABLISHING COLLABORATIONS The Cures Acceleration Network was established to advance the development of high-need cures and reduce BiomedExperts BiomedExperts Enables social networking to help scientists Identify collaborators http://www.biomedexperts.com share data and search for potential and expertise; share barriers to translation by providing new funding mechanisms and fl exibility to help NIH more effectively manage collaborators based on their areas of data projects. expertise and professional networks. The National Center for Advancing Translational Sciences brings together many of the above listed components, Collaboration and National Institutes of Health Provides assistance to investigators who are Provide information Team Science: http://tinyurl.com/75r8foz participating on, leading, or contemplating on collaboration and among others, into one cohesive entity. It will support partnerships to provide resources for investigators at all stages A Field Guide building a research team. Topics include team science along the pipeline and enhance training and disciplines related to translational sciences, such as clinical pharmacology. building a research team, developing a The new Center is not intended to duplicate current activities in the other NIH Institutes and Centers, but rather to shared vision, sharing recognition and credit, facilitate them and catalyze collaborations across the NIH enterprise. and handling confl ict. Collaborative National Institutes of Health Provides a template for developing a Facilitate Agreement http://tinyurl.com/cdohgwm collaborative agreement that explicitly collaborative Template states the team’s expectations, goals, and agreements values. This template is contained in NIH’s “Collaboration and Team Science: A Field Guide” (see above). Global Centers Pfi zer, University of California Network of partnerships with academic Foster collaboration for Therapeutic San Francisco medical centers (AMCs) designed to develop to promote drug Innovation http://tinyurl.com/4mlmdhp biologic therapeutic candidates. Centers are development jointly staffed by Pfi zer employees and basic the current research environment—one challenges can limit professional interest in the and translational scientists and doctoral that encourages specialization and rewards fi eld and hamper the translational enterprise. candidates from AMCs. Pfi zer provides investigators with access to its resources individual achievement and hypothesis-driven To address these issues, the Federation of and incentivizes participation through research. In addition, basic investigators American Societies for Experimental Biology milestone payments, publishing rights, and may face inadequate funding, resources, or (FASEB) held a symposium March 24-25, intellectual property use. infrastructure for developing translational 2011, that brought together basic and clinical research programs. Furthermore, they often lack research trainees and scientists, department suffi cient experience with essential methods and heads, and senior leaders from diverse academic techniques, as well as with complex regulatory research institutions; the leadership of private requirements, to be effective in this realm. These and public research funding organizations,
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FASEB Report Layout.FINAL.indd Spread 9 of 28 - Pages(42, 3) 3/20/12 5:19 PM pharmaceutical research organizations, and track record of supporting fundamental science Patrick Stover, PhD Matt Walter, MD scientifi c societies; and scientifi c publishers. and an interest in advancing human health Professor and Director Assistant Professor of Medicine Division of Nutritional Sciences Washington University School of Medicine (For the agenda and a full list of registrants, and the treatment of disease. To supplement Cornell University [email protected] see Appendix 1 and Appendix 2.) Meeting information provided in the presentations, [email protected] participants explored the benefi ts of engaging FASEB conducted a survey of meeting Ena Wang, MD Nancy Sung, PhD Staff Scientist basic scientists in translational research, the participants and nearly 2,000 FASEB society Senior Program Offi cer Clinical Center Department of Transfusion Medicine obstacles that stand in their way, and the role scientists. This report describes the major survey Burroughs Wellcome Fund National Institutes of Health that research institutions, funders, professional results (see survey insert, page 22), summarizes [email protected] [email protected] societies, and scientifi c publishers can play to the proceedings of the meeting, and offers a Bernard Talbot, MD, PhD Scott Weir, PharmD, PhD help basic scientists overcome these obstacles. practical set of recommendations for engaging Medical Offi cer Director The meeting was hosted by the Howard basic scientists in translational research. FASEB’s National Center for Research Resources Institute for Advancing Medical Innovation Hughes Medical Institute (HHMI) in Chevy goal is to foster the creation of an environment National Institutes of Health University of Kansas [email protected] [email protected] Chase, Maryland, and was co-sponsored by that encourages basic scientists to consider the the Burroughs Wellcome Fund, the U.S. translational potential of their work and to William Talman, MD Jennifer Westendorf, PhD Department of Veterans Affairs, the Doris Duke pursue opportunities to apply their knowledge Professor of Neurology and Neuroscience Associate Professor University of Iowa Mayo Clinic Charitable Foundation, and Merck Sharp & and expertise to investigations directly relevant [email protected] [email protected] Dohme Corp. All fi ve organizations have a long to improving human health and treating disease. Thomas Tuschl, PhD Andrea Widener, MA Associate Professor and Head of the Laboratory Science Writer for RNA Molecular Biology Howard Hughes Medical Institute The Rockefeller University [email protected]
Mark Tykocinski, MD Heng Xie, MD, MPH, PhD Dean Supervisory Medical Offi cer Jefferson Medical College National Center for Research Resources [email protected] National Institutes of Health [email protected] Rod Ulane, PhD NIH Research Training Offi cer Wen Xie, MD, PhD National Institutes of Health Associate Professor [email protected] University of Pittsburgh [email protected] Leslie Vosshall, PhD Robin Chemers Neustein Professor Liming Yang, PhD Head of the Laboratory of Neurogenetics and Behavior Program Offi cer The Rockefeller University National Center for Research Resources National Institutes of Health Daniel Wagenaar, PhD [email protected] Broad Senior Research Fellow in Brain Circuitry California Institute of Technology Jennifer Zeitzer [email protected] Director of Legislative Relations Federation of American Societies for Daniel Wagner, PhD Experimental Biology Assistant Professor, Department of Biochemistry [email protected] and Cell Biology Rice University [email protected]
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FASEB Report Layout.FINAL.indd Spread 10 of 28 - Pages(4, 41) 3/20/12 5:19 PM Marc Reitman, MD, PhD Douglas Sheeley, ScD Branch Chief Senior Scientifi c Offi cer The Benefi ts of Engaging in National Institute of Diabetes and Digestive National Center for Research Resources and Kidney Diseases National Institutes of Health Translational Research National Institutes of Health [email protected] [email protected] Susan Shurin, MD Makeda Richardson Acting Director The ultimate goal of translational biomedical research is to improve human Program Assistant National Heart, Lung, and Blood Institute health—an outcome that benefi ts all of society. But participating in Graduate Science Education National Institutes of Health translational science also has more direct and immediate rewards for Howard Hughes Medical Institute [email protected] individual investigators and the institutions that support their work. [email protected] Hadley Sikes, PhD Three teams of panelists—paired as basic scientists and senior leaders Rose Marie Robertson, MD Assistant Professor from the same university—discussed these benefi ts from their Chief Science Offi cer Massachusetts Institute of Technology respective vantage points. American Heart Association [email protected] [email protected] David Skorton, MD Benefi ts to Scientists Michael Rosenblatt, MD President The opportunity to conduct research that has an impact on human health is Executive Vice President Cornell University a signifi cant factor in many scientists’ decisions to participate in translational Chief Medical Offi cer [email protected] research. Nearly three-quarters of the respondents to FASEB’s survey indicated Merck & Co. Paul Dechow, PhD, Jacqueline Slavik, PhD that they initially embarked on translational work because they wanted to have [email protected] Professor and Vice Executive Director an impact on a particular disease or condition, and more than half wanted to Theodora Ross, MD, PhD Biomedical Research Institute Chair, Department of Professor Brigham and Women’s Hospital Biomedical Sciences, have an impact on human health in general. (See survey insert, page 22.) This University of Michigan [email protected] Baylor College of sentiment was echoed by Dirk Schnappinger, PhD, Associate Professor, Weill [email protected] Dentistry, Texas A&M Cornell Medical College, who is working to validate new targets for the discovery Bonnie Sloane, PhD Health Science Center of drugs to treat tuberculosis. He noted that he and his team, which includes Doris Rubio, PhD Distinguished Professor & Chair Professor of Medicine Wayne State University collaborators from 13 institutions around the world, “are motivated by having an University of Pittsburgh [email protected] impact on global health and can attract people who share that desire.” Likewise, [email protected] for Michael Dyer, PhD, an HHMI Early Career Scientist and a basic biologist John Smith, MD, PhD, MMM, DSC (Hon) Alisa Schaefer, PhD Director, Division of Laboratory Medicine studying retinal development at St. Jude Children’s Research Hospital, the Advisor for Global Outreach Professor of Pathology realization that the tens of thousands of papers on the genetics of retinoblastoma National Institutes of Health University of Alabama at Birmingham had not yet affected the way patients with the disease are treated “fundamentally [email protected] [email protected] changed the direction of [his] career and the research direction of [his] lab.” Dirk Schnappinger, PhD Mark Sobel, MD, PhD (See Box B.) Associate Professor of Microbiology and Immunology Executive Offi cer Thomas Tuschl, PhD, Associate Professor and Head of the Laboratory for Weill Cornell Medical College American Society for Investigative Pathology RNA Molecular Biology at The Rockefeller University, also wanted to apply [email protected] [email protected] his science to the study of disease; partnering with clinicians helped him to do Jacob Schumacher Anita Miller Sostek, PhD that. Trained as a basic scientist, he obtained his doctoral degree in chemistry, Legislative Aide Vice President for Scientifi c Review and Operations conducted postdoctoral work in biochemistry, and then became interested in The American Association of Immunologists Autism Speaks the therapeutic applications for gene silencing through the discovery of sRNAs [email protected] [email protected] and microRNAs as regulators of gene expression. His current work is focused on Harry Shamoon, MD Tyrone Spady, PhD defi ning the molecular pathology leading to specifi c diseases and developing Associate Dean Science Policy Analyst targeted approaches suitable for therapeutic interventions. Clinical and Translational Research Federation of American Societies for Experimental Tuschl had developed an appreciation for translational science and its Albert Einstein College of Medicine Biology [email protected] [email protected] challenges while working with the pharmaceutical industry. As a cofounder and scientifi c advisor to Alnylam Pharmaceuticals and Regulus Therapeutics,
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FASEB Report Layout.FINAL.indd Spread 11 of 28 - Pages(40, 5) 3/20/12 5:19 PM Thomas Miller, PhD Margaret Offermann, MD, PhD Box B: Making a Diff erence Program Director Principal Taking the Challenges of the Clinic Back to the Laboratory National Institute of Neurological Disorders and Stroke The Salutramed Group National Institutes of Health [email protected] [email protected] Frederick Ognibene, MD When Michael Dyer, PhD, fi rst arrived at St. Jude as a junior faculty member nine years ago, Daria Mochly-Rosen, PhD Deputy Director Educational Affairs & Strategic he was the head of a basic developmental neurobiology research laboratory. One day, while Senior Associate Dean for Research Partnerships deciding how to set up his laboratory space, there was a knock at his door. Two clinicians Professor Chemical & Systems Biology National Institutes of Health Stanford University [email protected] who treat retinoblastoma patients asked him to spend some time with them in the clinic. He [email protected] realized that after spending fi ve years at a major medical center and studying normal eye Alex Ommaya, DSc development and genetic mutations of the eye, he had never once met a clinician, patient, or Katie Moore, PhD Director Translational Research Manager, Science Policy patient’s family. He eagerly accepted the opportunity. U.S. Department of Veterans Affairs The Endocrine Society [email protected] [email protected] Dyer knew that Rb gene mutations cause retinoblastoma, a rare childhood cancer with only Rebecca Osthus, PhD Mariana Morris, PhD 300 cases per year in the United States. But when he asked the clinicians if the tens of Science Policy Analyst Professor and Chair thousands of papers available on PubMed on the Rb gene and pathway had any impact on American Physiological Society Assistant Vice President for Graduate Studies [email protected] how patients are treated, they replied that they had no impact whatsoever. This surprising Wright State University response led him to change the direction of his career and the research direction of his [email protected] F. Nina Papavasiliou, PhD, laboratory. Cynthia Morton, MD Associate Professor and Head of the Laboratory Professor of Obstetrics/Gynecology and Pathology of Lymphocyte Biology To Dyer, the reason these basic research papers had not been translated into new therapies Brigham and Women’s Hospital The Rockefeller University was obvious: there was a lack of good animal models for this disease. Researchers had Harvard Medical School [email protected] tried to develop a retinoblastoma model by deleting the Rb gene from the mouse genome, [email protected] Todd Peterson, PhD but the manipulation did not cause the mouse to develop retinoblastoma. Unbeknownst to Karen Mowrer, PhD Assistant Professor them at the time, another protein, p107, is able to compensate for Rb in the mouse. When Legislative Affairs Offi cer Vanderbilt University both Rb and p107 are deleted from the mouse genome, retinoblastoma develops in about Federation of American Societies for Experimental [email protected] 50 percent of the animals. Using this model, he was able to test different therapeutics against Biology [email protected] Sharma Prabhakar, MD, MBA, FACP the disease. In doing so, Dyer applied what he learned from his clinical colleagues about Professor and Chief of Nephrology the actual course of treatment in patients (i.e., clinical reality) and tested combinations of James Musser, MD, PhD Vice-Chair, Dept of Medicine broad-spectrum systemic chemotherapeutics in a similar manner in his mice. After going Chair Texas Tech University Health Sciences Center Department of Pathology and Laboratory Medicine [email protected] through eight different combinations of drugs and comparing them to the current standard The Methodist Hospital of care, Dyer and his colleagues found a combination that seemed to be better than what [email protected] M. Renee Prater, PhD, DVM children currently were receiving. St. Jude started a new fi ve-year clinical trial based on those Associate Professor and Chair of Immunology Elizabeth Myers, PhD data. Although going from nothing to a new clinical trial in about 18 months was satisfying, Edward Via College of Osteopathic Medicine Program Director [email protected] Dyer hoped to do better. He wanted to develop a more targeted chemotherapy that could be Doris Duke Charitable Foundation delivered locally to the eye and result in fewer side effects. [email protected] Alice Ra’anan Director of Science Policy Searching for a drug target, Dyer’s team discovered that patients with retinoblastoma Lee Nadler, MD American Physiological Society Dean of Clinical and Translational Research [email protected] have increased levels of MDMX, which sequesters p53, a tumor suppressor, and leads to Harvard Medical School cell proliferation and tumor development. MDMX is amplifi ed in 65 percent of patients and [email protected] J. Usha Raj, MD epigenetically turned on in the rest. Professor and Head Kim Ngo University of Illinois at Chicago Public Affairs Assistant Now having a target to go after, Dyer and colleagues developed a model in which the [email protected] Federation of American Societies for Experimental MDMX gene was conditionally over expressed in the mice that develop retinoblastoma. This Biology resulted in a much more aggressive disease in these animals—providing a new model to [email protected]
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FASEB Report Layout.FINAL.indd Spread 12 of 28 - Pages(6, 39) 3/20/12 5:19 PM Henry Krause, PhD Marc Malandro, PhD he learned a great deal about genetic diseases, Professor Associate Vice Chancellor for Technology Management the molecular causes underlying disease, and University of Toronto and Commercialization [email protected] University of Pittsburgh validation of drug targets, and he started to look [email protected] for translational research opportunities that Joel Kupersmith, MD were within reach of his academic laboratory. Chief Research & Development Offi cer Francesco Marincola, MD test chemotherapeutics. Not wanting to rely U.S. Department of Veterans Affairs Tenured Senior Investigator solely on a genetic model, they also developed His commitment to the fi eld increased when [email protected] Clinical Center Department of Transfusion Medicine a “xenographic” mouse model in which human a group of highly motivated Clinical Scholars National Institutes of Health joined his laboratory. These clinicians were Michael Kurilla, MD, PhD [email protected] tumor cells are transplanted to an eye of an Director immunocompromised mouse. This results in attracted to his work primarily because of its National Institute of Allergy and Infectious Diseases Priscilla Markwood, CAE virtually 100 percent engraftment with tumors specialized methods for characterizing small Director of Scientifi c Affairs, Communications National Institutes of Health expressing high levels of MDMX. Collaborations regulatory RNAs and their targets, but their [email protected] & Society Services American Society for Investigative Pathology with his chemical biology colleagues, who projects rapidly expanded and touched on Jennifer Kwan [email protected] were able to synthesize an MDMX inhibitor, and many aspects of gene regulation. He had not Policy Chair Bettie Sue Masters, PhD clinicians, who provided medical information anticipated the strong interest that the clinical American Physician Scientists Association investigators would have in basic science and M.D.-Ph.D. Candidate The Robert A. Welch Distinguished Chair in Chemistry and tumor specimens, enabled Dyer to begin a University of Texas Health Science Center San Antonio Medical Scientist Training Program preclinical trial focused on inhibiting MDMX. new methodologies, and he found that pairing [email protected] University of Illinois at Chicago each clinician with a basic investigator resulted Dyer believes that the process by which basic [email protected] Donald McClain, MD, PhD in a considerable amount of synergy between Program Director investigators can translate their discoveries into Megan Lassig the two. University of Utah clinical applications could be emulated at most Program Assistant Without the expertise that the clinicians [email protected] major medical or academic research centers. The Howard Hughes Medical Institute brought to his laboratory, Tuschl says he might [email protected] building blocks important for driving translation, Dennis McKearin, PhD have never understood how to operate and Senior Scientifi c Offi cer such as strong basic science departments, animal Anh-Chi Le, PhD devise experiments relevant to translational Howard Hughes Medical Institute research facilities, pharmacology and pathology Program Offi cer [email protected] medicine. By working with human tissue Howard Hughes Medical Institute departments, and clinical trial support are already samples, observing the variation among [email protected] Matthew McMahon, PhD in place. He also noted that some translational individuals and in sample collection, following Senior Advisor for Translational Research work can be done with relatively few resources, Stephanie Lederman, EdM National Eye Institute the clinicians’ progress at the bench, and Executive Director if one acts creatively. He received no support from National Institutes of Health accessing their data, he learned how to adapt American Federation for Aging Research [email protected] St. Jude to fund these studies directly. Rather, [email protected] Dyer built on a one-year pilot grant of $50,000 and his methods to study hundreds of patient and Sally McNagny, MD, MPH control samples. In return, the scholars have Grace Lee, PhD cobbled the rest together through other sources. Vice President found it helpful to train with a basic scientist, Pharmacology/Toxicology Reviewer The Medical Foundation, a division of HRiA U.S. Food and Drug Administration [email protected] The challenge, he said, is changing the culture. which offered them a completely new strategy [email protected] Emphasizing the value of translational research for understanding biological phenomena. Elizabeth McNally, MD, PhD to both basic and clinical scientists, encouraging Yung Lie, PhD Professor of Medicine and Human Genetics For basic biologists, engaging in Scientifi c Director Director, Institute for Cardiovascular Research communication between basic and clinical translational research has benefi ts that go Damon Runyon Cancer Research Foundation Director, Cardiovascular Genetics Clinic scientists, mentoring, and understanding the beyond contributing to understanding and [email protected] President Elect clinical reality of disease progression and treating human disease. It helped Leslie Vosshall, American Society for Clinical Investigation therapeutic interventions are all important for Yvonne Maddox, PhD [email protected] PhD, Robin Chemers Neustein Professor and Deputy Director increasing participation in translational research Head of the Laboratory of Neurogenetics and Francis Miller, MD National Institute of Child Health and and ultimately improving human health. Behavior at The Rockefeller University, to Human Development Associate Professor of Medicine National Institutes of Health University of Iowa learn more about her fi eld. Trained as a basic [email protected] [email protected] biomedical researcher, Vosshall used insects to
38 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 7
FASEB Report Layout.FINAL.indd Spread 13 of 28 - Pages(38, 7) 3/20/12 5:19 PM study smell for many years before turning to results; exposure to new fi elds and methods Lawrence Green Jennifer A. Hobin, PhD people where, she said, “all the interesting action leading to new projects; and rapid publication Communications Specialist Director of Science Policy Federation of American Societies for Experimental Federation of American Societies for Experimental is.” Today, she studies how humans discriminate rate. Indeed, Wagner noted that three papers Biology Biology among smells, how genetic variation in humans were generated from the nanobubble project [email protected] [email protected] alters how they perceive odors, and how in the year preceding the meeting, equal to the Nadja Grobe, PhD Marybeth Howlett, MEM mosquitoes react to our smell. Her laboratory output of all of his other projects combined. Postdoctoral Research Fellow Managing Director is one of the biggest users of the Rockefeller Wright State University The Society of Nuclear Medicine outpatient clinic and has run upwards of 1,500 In sum, participation in translational [email protected] [email protected] volunteers through these olfaction studies. research benefi ts basic scientists by: Lauren Gross, JD Valerie Hu, PhD Director of Public Policy and Government Affairs Professor of Biochemistry and Molecular Biology Pursuing translational research also had • Enabling them to contribute to the benefi ts for Daniel Wagner, PhD, Assistant The American Association of Immunologists The George Washington University Medical Center understanding of human health and disease [email protected] [email protected] Professor, Department of Biochemistry and and to participate in the development of Lisa Guay-Woodford, MD Geoff Hunt, PhD Cell Biology at Rice University. A basic solutions to medical and public health developmental biologist working in zebrafi sh, Professor and Vice Chair Science Policy Fellow problems, which can be a source of University of Alabama at Birmingham American Society for Biochemistry & Molecular Biology Wagner embarked on a collaborative project intellectual inspiration and stimulation. [email protected] [email protected] with a physicist after encountering him • Providing opportunities to develop their Kathi Hanna, PhD Richard Insel, MD reading one of Wagner’s posters in the hallway. Science and Health Policy Consultant Chief Scientifi c Offi cer The physicist was working on a theranostic own science and learn new methods, which [email protected] Juvenile Diabetes Research Foundation (therapeutic–diagnostic) application for can lead to new projects, fresh directions for [email protected] existing projects, and faster publication rates. Rebecca Hartley, PhD plasmonic nanobubbles, in which gold particles Associate Professor Rebecca Jackson, MD are excited by short laser pulses to generate • Promoting collaborations with clinicians, University of New Mexico Health Sciences Center Associate Dean for Clinical Research transient vapor bubbles. The biologist and the clinical researchers, and basic investigators [email protected] The Ohio State University [email protected] physicist joined up to test the concept that in other disciplines, which can ignite shared Philip Haydon, PhD these nanobubbles could be used to identify passion, provide exposure to new areas of Annetta and Gustav Grisard Professor and Joseph Kemnitz, PhD cells based on their expression of specifi c cell Chair Department of Neuroscience Director, Translational Technologies and Resources science, and generate new ideas. Tufts University School of Medicine University of Wisconsin Madison surface molecules and to destroy specifi c cells in [email protected] [email protected] a zebrafi sh. The team used these nanobubbles • Providing opportunities to mentor clinical targeted to the EGF receptor and was able colleagues in basic science methods. Anthony Hayward, MD, PhD Khandan Keyomarsi, PhD Director, Division for Clinical Research Resources Professor to destroy prostate cancer cells within a host National Center for Research Resources University of Texas MD Anderson Cancer Center embryo. This was the fi rst step—proof of Benefi ts to Institutions National Institutes of Health [email protected] principle—that the theranostic method can be Institutions also benefi t from creating an [email protected] Robert Kimberly, MD used in vivo as a potential diagnostic tool and environment conductive to translational science. Joseph (JR) Haywood, PhD Senior Associate Dean for Research ultimately for targeted therapy. Their efforts help their scientists by facilitating Chair, Deparment of Pharmacology University of Alabama at Birmingham “As I saw the group that was being access to resources that they may not have had Michigan State University [email protected] [email protected] assembled around this plasmonic nanobubble before and connecting them to collaborators Stephen Korn, PhD project, I really began to think that there were with whom they share research interests, Terry Hébert, PhD Director of Training and Career Development some serious benefi ts for me, as a basic scientist, but otherwise may not have met. These Associate Professor National Institute of Neurological Disorders and Stroke McGill University National Institutes of Health and the potential to move this technology synergies move research forward, benefi tting [email protected] [email protected] forward and ultimately translate it into the the individual and his or her institution. For clinic,” said Wagner. Among the benefi ts he example, at The Rockefeller University, Vosshall Mary J.C. Hendrix, PhD Sally Kornbluth, PhD President & Scientifi c Director Vice Dean for Research cited were participation in a quickly moving noted that in order to carry out her studies on Children’s Memorial Research Center Duke University School of Medicine multi-investigator project that produced novel the sense of smell, she increasingly has to rely [email protected] [email protected]
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FASEB Report Layout.FINAL.indd Spread 14 of 28 - Pages(8, 37) 3/20/12 5:19 PM Anne M. Deschamps, PhD Mary C. Farach-Carson, PhD on the resources that are funded by Rockefeller’s Science Policy Analyst Associate Vice Provost for Research CTSA. Support for statistical work comes from Federation of American Societies for Experimental Rice University The Human as the Best Biology [email protected] its biostatisticians, and its facilitation offi ce [email protected] has helped shepherd protocols from initial Animal Model Fred Finkelman, MD Paul DiCorleto, PhD McDonald Professor of Medicine conceptualization to fi nal approval. She has had Chair, Lerner Research Institute Professor of Pediatrics to lean heavily on the clinical staffi ng in the “I come from a family of clinical Cleveland Clinic University of Cincinnati College of Medicine ffi [email protected] outpatient clinic, and the Institutional Review physicians, and there has been, [email protected] Board (IRB) has helped improve the quality Michael Fleming, MD, MPH always, a little bit of a mistrust from Loretta Doan, PhD Professor of her protocols. Working with Rockefeller’s Director, Science Policy Northwestern University hospital, she was able to obtain access to the my end [as] the basic scientist. I The Endocrine Society m-fl [email protected] [email protected] darkened space that she needed for her own always felt that clinical research was Susan Foy research by acquiring repurposed rooms that Chhanda Dutta, PhD either not rigorous enough or boring. Graduate Student had been used for sleep studies. Her work would Chief, Clinical Gerontology Branch Cleveland Clinic Lerner College of Medicine of Case And my parents and siblings always Division of Geriatrics and Clinical Gerontology Western Reserve University not have been possible without these resources. National Institute on Aging [email protected] A focus on translational research also felt that basic research was not really National Institutes of Health benefi ts trainees and early career scientists. [email protected] Martin Frank, PhD useful to them when they would see, Executive Director It provides important training opportunities American Physiological Society maybe, the outcome of it in their Steven Dworkin, PhD for graduate students and postdoctorates and Professor and Chair of Psychology [email protected] Western Illinois University may help to attract new talent into biomedical practice 10, 20, or 30 years later—if Maryrose Franko, PhD [email protected] Senior Program Offi cer research. Cindy Farach-Carson, PhD, Vice they’re lucky. Yet their patients need Michael Dyer, PhD Howard Hughes Medical Institute Provost for Translational BioScience, Rice [email protected] an answer now. I have had a clinical Member University, noted that translational research St. Jude Children’s Research Hospital Richard Galbraith, MD, PhD appeals to today’s generation of university fellow in my laboratory. This has [email protected] Professor of Medicine and Associate Dean students—many of whom want to work on University of Vermont provided a little dose of humility David J. Eckstein, PhD [email protected] “big, real world problems.” on both ends and fostered the idea Senior Health Scientist Administrator Farach-Carson also emphasized that Offi ce of Rare Diseases Research Bill Galey, PhD that we can, in fact, both make an National Institutes of Health Director of Graduate and Medical Education Programs establishing the infrastructure to conduct [email protected] Howard Hughes Medical Institute translational research provides opportunities impact quickly while learning from [email protected] for all of an institution’s investigators—not just Joel Ernst, MD clinical studies. From our clinical Professor Nao Gamo, MPhil those working on bench-to-bedside projects. NYU School of Medicine Graduate Student The collaboration necessary for conducting samples, we’ve learned a lot about [email protected] Yale University [email protected] this kind of work involves sharing expensive transcriptome editing that we Sindy Escobar Alvarez, PhD equipment, forming equipment cores, and Howard Garrison, PhD Program Offi cer for Medical Research probably wouldn’t have trusted had Director, Offi ce of Public Affairs developing policies for sharing, which can work Doris Duke Charitable Foundation Federation of American Societies for Experimental to everyone’s advantage. For example, Rice’s $9 it come from mouse studies alone. [email protected] Biology [email protected] million supercomputer from IBM came with Mary Estes, PhD F. Nina Papavasilou, PhD, the condition that it be shared in an affordable Associate Professor and Head of the Professor of Molecular Virology and Co-Director Eric Green, MD, PhD Graduate Program in Translational Biology and Director way with the Texas Medical Center and others Laboratory of Lymphocyte Biology, Molecular Medicine National Human Genome Research Institute outside the center. The Rockefeller University Baylor College of Medicine National Institutes of Health [email protected] [email protected]
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FASEB Report Layout.FINAL.indd Spread 15 of 28 - Pages(36, 9) 3/20/12 5:19 PM Scott Campbell, PhD Barry Coller, MD Executive Director and CEO Physician-in-Chief and Vice President for Medical Affairs Foundation for the National Institutes of Health The Rockefeller University [email protected] [email protected]
Maria Teresa Canto, DDS, MS, MPH Francis Collins, MD, PhD Health Scientist Administrator Director National Center for Research Resources National Institutes of Health National Institutes of Health [email protected] [email protected] Angela Colmone, PhD Sean Carroll, PhD Associate Editor Vice President for Science Education Science Translational Medicine Howard Hughes Medical Institute [email protected] [email protected] Leslie Cooper, RN, BSN, MPH, PhD Robert Carter, MD, PhD Program Offi cer Deputy Director National Center for Research Resources National Institute of Arthritis and Musculoskeletal National Institutes of Health and Skin Diseases [email protected] National Institutes of Health [email protected] Milton Corn, MD Deputy Director for Research and Education David Skorton, MD, President, Cornell University and Dirk Schnappinger, PhD, Associate Professor, Weill Cornell Medical College Gail Cassell, PhD National Library of Medicine Visiting Professor National Institutes of Health Department of Global Health and Social Medicine [email protected] Harvard Medical School and In addition to benefi ting their scholars, university, state, and regional priority. The Kyle Covington Vice President of TB Drug Discovery investing in translational research has a positive center’s goal was to capitalize on the strengths Graduate Student Infectious Disease Research Institute in Seattle Baylor College of Medicine impact on institutions as a whole. Fostering an of the university and on regional assets to [email protected] environment conducive to translation advances become a national leader in the discovery and [email protected] John Chatham, PhD the core missions of biomedical research advancement to Phase I of promising anticancer James M. Crawford, MD, PhD Professor and Director Senior Vice President institutions, stated Barry Coller, MD, Vice agents. Molecular and Cellular Pathology Pathology & Laboratory Medicine President for Medical Affairs and Physician- Before the center was started, the University University of Alabama at Birmingham North Shore-Long Island Jewish Health System [email protected] in-Chief, The Rockefeller University Medical of Kansas had one of the top schools of Laboratories Center. Successes in the development of new pharmacy in the United States and strong Clement Chow, PhD [email protected] drugs, devices, and procedures attract patients leadership in medicinal and pharmaceutical Postdoctoral Scientist Meredith Crosby, PhD Cornell University who want to benefi t from cutting-edge care, chemistry. It also had conducted research that Postdoctoral Scientist [email protected] and they attract funding from donors with an led to the commercialization of several drug Yale University/Procter & Gamble interest in supporting promising work that products. But none of those products had been Ida Chow, PhD [email protected] Executive Offi cer could lead to new treatments. tested in patients at the university’s medical Geraldine Dawson, PhD Society for Developmental Biology Scott Weir, PharmD, PhD, Director, center, which is located 42 miles away from the Chief Science Offi cer [email protected] Institute for Advancing Medical Innovation, School of Pharmacy. Additionally, its cancer Autism Speaks University of Kansas Cancer Center, described biology program was in its infancy and did not Stanley Cohen, MD [email protected] Chair the evolution of the extensive network have a rich, potential source of novel cancer Paul Dechow, PhD Department of Pathology Professor and Vice-Chair of partners that formed around efforts to drug targets. To achieve its goal of becoming UMDNJ-New Jersey Medical School establish a center of excellence for cancer at one of the top university-based cancer centers Department of Biomedical Sciences [email protected] Baylor College of Dentistry his institution. Establishing a National Cancer in bench-to-bedside translation, the university Texas A&M Health Science Center Institute-designated cancer center became a identifi ed the need to establish translational [email protected]
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FASEB Report Layout.FINAL.indd Spread 16 of 28 - Pages(10, 35) 3/20/12 5:19 PM Appendix 2: Meeting Participants research competencies and capabilities. In sum, institutions benefi t from Pharmaceutical industry veterans were recruited fostering translational research to establish best practices. In addition to programs by: working with the University of Kansas cancer Myles Akabas, MD, PhD Sanjay Bidichandani, MBBS, PhD biologists, efforts to establish partnerships with • Connecting their investigators to resources Professor of Physiology & Biophysics Vice President for Research and collaborators and facilitating affordable Muscular Dystrophy Association industry, academia, government, and disease Director, Medical Scientist Training Program access to expensive shared equipment and Albert Einstein College of Medicine of Yeshiva University [email protected] philanthropy collaborators were initiated to gain [email protected] facilities. Linda Birnbaum, PhD access to novel drug targets. Robert Alpern, MD Director The university has refi ned its role in cancer • Providing unique training opportunities Dean National Institute of Environmental Health Sciences therapeutics. With a focus on unmet medical for undergraduates, graduate students, and National Institutes of Health Yale School of Medicine needs such as rare and neglected diseases and postdoctorates and encouraging new talent to [email protected] [email protected] pediatrics, it has established translational enter biomedical research. Mitsi Blount, PhD Bruce Altevogt, PhD Assistant Professor research processes to discover and develop novel Senior Program Offi cer • Promoting the development of new drugs, Emory University drugs as well as identify new uses for approved Institute of Medicine devices, and other medical interventions, [email protected] and abandoned drugs. It has integrated and [email protected] which advances their biomedical research even rebuilt core facilities, developed a strategy Jeffrey Bluestone, PhD missions, attracts patients, and enhances their Barbara Alving, MD, MACP Professor, Executive Vice Chancellor, and Provost for handling technology transfer, put proof-of- Director University of California San Francisco status. National Center for Research Resources [email protected] concept funding strategies in place, and formed National Institutes of Health multidisciplinary and multi-organizational • Gaining access to new funding streams [email protected] Richard Bockman, MD, PhD teams managed by industry-experienced project supporting both institutional and individual Professor of Medicine Margaret Anderson, MS Weill Medical College/Hospital for Special Surgery managers. The center also invested heavily in projects. Executive Director [email protected] project managers who oversee all aspects of • Attracting public-private partnerships and FasterCures translation, freeing up investigators to focus [email protected] Jo Boughman, PhD leveraging federal and nonfederal resources. Executive Vice President on the science, and it is looking beyond its James C. Austin, PhD American Society of Human Genetics own walls for promising ideas to move drug [email protected] Editor, Science Careers development forward. AAAS Challenges to Engaging Pamela Bradley, PhD [email protected] By demonstrating successes in translational Associate Director of Science Policy research, the university was able to attract top- Basic Scientists in Robert Berdahl, PhD American Association for Cancer Research President [email protected] notch cancer researchers who are interested Translational Research Association of American Universities Linda Brady, PhD in drug discovery and development. It has [email protected] Director, Division of Neuroscience and Basic Behavioral recruited more than 230 years of pharmaceutical Meeting participants noted that numerous Science challenges can discourage or prevent basic Daniel Bernard, PhD experience over the past fi ve years, from National Institute of Mental Health investigators from participating in translational Associate Professor [email protected] investigators pursuing target validation to those McGill University doing clinical testing. Its collaborations have science. These include differences in culture [email protected] Brian Brewer brought in a broad array of new funding sources and mindset between basic and clinical Director of Communications researchers, insuffi cient and/or nonsupportive Jim Bernstein, MPA Cancer Research Institute to support additional collaborations, including Director [email protected] those involving government and philanthropic infrastructure, diffi culty developing and Government & Public Affairs sustaining collaborations, inadequate training, American Society for Pharmacology & Experimental PJ Brooks, PhD organizations and those related to state Therapeutics Program Offi cer and Adjunct Investigator economic development initiatives. The center insuffi cient funding, and lack of other incentives [email protected] National Institute on Alcohol Abuse and Alcoholism brought three new therapies to the clinic in and rewards. and Offi ce of Rare Diseases Research National Institutes of Health 2009, moved one forward in 2010, and brought [email protected] fi ve more to the clinic in 2011.
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FASEB Report Layout.FINAL.indd Spread 17 of 28 - Pages(34, 11) 3/20/12 5:19 PM Culture and Mindset their work or discuss a particular topic. As a Breakout 2: Facilitating productive collaborations Small Auditorium (K202) Basic scientists may see their controlled, result, people who had no interest in diseases are Moderator: Richard Bockman, MD, PhD, Professor of Medicine, now gaining interest. Haydon has observed that Endocrine Division, Weill Cornell Medical College, hypothesis-driven research as more rigorous and Chief of the Endocrine Service, Hospital for Special Surgery than the goal-directed or descriptive research faculty members who are surrounded by others with a translational focus are more likely to Panelists: Gail Cassell, PhD, Visiting Professor, often conducted with humans in clinical Department of Global Health and Social Medicine, research settings. On the other hand, clinical develop the interests and skills needed to adapt. Harvard Medical School and Vice President of TB Drug Discovery, scientists may view their work as superior Infectious Disease Research Institute in Seattle insofar as it has greater relevance to human Insuffi cient Infrastructure to Scott J. Weir, PharmD, PhD, Director, Institute for Advancing Medical Innovation, University of Kansas Cancer Center health and disease. These perceived differences Develop Clinical Protocols, Facilitate Lee M. Nadler, MD, Virginia and D.K. Ludwig Professor not only inhibit collaborations between the Exchanges, and Enable Handoffs of Medicine, Harvard Medical School two groups, but also they may discourage Many basic scientists (and some clinical Jeffrey Bluestone, PhD, A.W. and Mary Margaret Clausen basic investigators from pursuing translational scientists) fi nd the pathway to clinical Distinguished Professor, Executive Vice Chancellor, and Provost, projects (see Box C). Even when basic scientists application fi lled with unfamiliar requirements University of California, San Francisco are open to translation, they do not necessarily and administrative procedures. Translational Breakout 3: Providing appropriate recognition and rewards D124 speak the same language as their clinical research involving human subjects may Moderator: Patrick Stover, PhD, Professor and Director, investigator counterparts because of differences require IRB and Privacy Board approval, Division of Nutritional Sciences, Cornell University in training and experience. reporting to data safety monitoring boards, Panelists: Sally Kornbluth, PhD, Vice Dean for Research, Institutions where translational research clinical trials registration, and specialized James B. Duke Professor, Pharmacology and Cancer Biology, Duke University School of Medicine fl ourishes have had to focus on overcoming the patient recruitment techniques. Working with cultural differences between basic and clinical Francesco Marincola, MD, Editor-in-Chief, industry adds a level of complexity, because Journal of Translational Medicine and Chief, scientists. They do this by creating opportunities confl ict of interest disclosures and data use Infectious Disease and Immunogenetics Section, for these investigators to share perspectives, see and intellectual property agreements must Department of Transfusion Medicine, the value in each other’s work, and embrace be drafted. As a result, carrying out a clinical National Institutes of Health Clinical Center both hypothesis testing and goal-oriented protocol can require more steps and time than Paul DiCorleto, PhD, The Sherwin-Page Chair, Cleveland Clinic Lerner Research Institute research. Philip Haydon, PhD, Professor and a laboratory-based protocol. Basic investigators Chair, Department of Neuroscience, Tufts usually do not have experience navigating these Breakout 4: The role of funding organizations D125 University School of Medicine, said he was requirements, and their universities may or Moderator: Nancy S. Sung, PhD, Senior Program Offi cer, Burroughs Wellcome Fund brought to Tufts to change the culture. When not have the expertise and infrastructure to he moved into the university’s neuroscience help them. Panelists: Barbara Alving, MD, Director, National Center for Research Resources, department, there was a focus on synaptic Some institutions have been proactive in physiology, but very little of the work had National Institutes of Health addressing these needs (see Box D). The Institute Sally McNagny, MD, MPH, FACP, Vice President, any translational thrust. He was faced with for Advancing Medical Innovation at the The Medical Foundation, a division of HRiA the challenge of identifying translational University of Kansas Cancer Center forms project Joel Kupersmith, MD, Chief Research and Development Offi cer, opportunities for faculty engaged in rigorous, management teams around technologies ripe for Veterans Health Administration basic work and helping to move them along translation. These teams provide investigators Dennis McKearin, PhD, Senior Scientifi c Offi cer, Howard Hughes Medical Institute that path. with the expertise they need in areas such as One way Haydon is trying to do this is drug discovery and development, industrial and 2:00-2:15 Break Great Hall by developing three faculty clusters that act philanthropic partnering, technology transfer, much like magnets. These clusters (in epilepsy, 2:15-3:00 Recommendations from breakout groups Auditorium and medicinal chemistry. This support ensures Breakout session moderators depression, and neurodegeneration) are open to that investigators can focus on their area of trainees, as well as faculty, and they meet every expertise: the science (see Figure 1). 3:00-3:15 Wrap up and next steps Auditorium two to three weeks for lunch to hear talks about Richard Galbraith, MD, PhD
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FASEB Report Layout.FINAL.indd Spread 18 of 28 - Pages(12, 33) 3/20/12 5:19 PM March 25, 2011 Box C: Going It Alone—Sometimes the Translational Scientist
7:30-8:15 am Breakfast Dining Room Is His or Her Own Best Ally 8:15-9:15 Table discussions: Sparking interest in translational research Dining Room Daria Mochly-Rosen, PhD, Professor and Senior Associate Dean for Research and Director of 9:15-11:30 What are the challenges to engaging basic scientists in Auditorium translational research? SPARK, Stanford University’s Translational Research Program, is a protein chemist conducting translational research. Early in her career, she designed rational inhibitors that could turn off Survey results John Smith, MD, PhD, MMM, DSc (Hon), heart cell enzymes one at a time and discovered enzymes that could change the rate at which Professor of Pathology and Director, Division of Laboratory Medicine, heart cells in culture beat. She thought this was an important fi nding that would be of interest University of Alabama at Birmingham to the heart research community, but when she presented her work at a scientifi c meeting, Perspectives across career levels she found the audience to be disinterested in heart rate regulation. Clinicians, she had been Moderator: John Smith, MD, PhD, MMM, DSc (Hon) told, already had ways of managing heart rate; they were concerned with problems such as cardiac ischemia. Panelists: Michael Dyer, PhD, Co-Leader, Developmental Therapeutics for Solid Malignancies Program, St. Jude Children’s Research Hospital Following the advice of a colleague, she invited into her laboratory a physician who wanted Daria Mochly-Rosen, PhD, Professor and Senior Associate Dean to learn basic research and from whom she could learn how to study more clinically relevant for Research and Director of SPARK, Stanford’s Translational Research Program, Stanford University, School of Medicine problems. Her work eventually led to the discovery of an inhibitor that when administered after Philip Haydon, PhD, Annetta and Gustav Grisard Professor and Chair, a heart attack reduces heart damage by 70 percent and prevents subsequent heart failure, Department of Neuroscience, Tufts University School of Medicine a fi nding that was demonstrated in mice, rats, guinea pigs, rabbits, and pigs. Patents were Robert J. Alpern, MD, Ensign Professor of Medicine and Dean, written and the results published. Yet no one was interested in her fi ndings. Why would this Yale School of Medicine not be useful in patients, she thought?
11:30-12:15 pm Lunch Dining Room When she brought her idea directly to industry, company after company turned her away. She 12:15-2:00 Breakout sessions: later realized that there were good reasons for this: while her work was attractive from a basic How can the research community address these challenges? research point of view, the barriers to executing it in patients were huge, and many steps had to be completed before reaching that goal. Mochly-Rosen reached out to her colleagues Breakout 1: Facilitating translational research training Auditorium for assistance, but rather than fi nding support, she was discouraged from pursuing this Moderator: William Galey, PhD, Director, Graduate and Medical Education Programs, Howard Hughes Medical Institute line of inquiry and from working with industry. Translational research, she was told, is not intellectually challenging, worthwhile, or good for her career. “Career progress in academia is Panelists: Khandan Keyomarsi, PhD, Professor, Department measured by how many papers are published and how much grant funding is received rather of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center than, for example, attempting to produce a new drug,” she said. (Initiative: TRIUMPH Postdoctoral Fellowship) But she persevered, formed her own company, KAI Pharmaceuticals, and spent a year as Matthew J. Walter, MD, Assistant Professor of Medicine and Genetics, Washington University School of Medicine its Chief Scientifi c Offi cer. She helped write an Investigational New Drug Application and (Initiative: Lucille P. Markey Special Emphasis Pathway launched a clinical trial. “Unlike my training in academia, where questions led to the research, in Human Pathobiology) in industry I learned to think about the fi nal product and work backwards, to identify what Mary Estes, PhD, Professor, Department of Molecular research needs to support such a product,” said Mochly-Rosen. The process was humbling, Virology and Microbiology, Baylor College of Medicine but also gratifying. “There is nothing more rewarding than [treating] the fi rst patient…or when (Initiative: HHMI Med into Grad) the trial is fi nished, looking at the data. It’s really a true manifestation of what basic research Rebecca Jackson, MD, Professor and Associate Dean, should eventually lead to.” College of Medicine, The Ohio State University (Initiative: CTSA Consortium Training and Career Development of Clinical/Translational Scientists)
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FASEB Report Layout.FINAL.indd Spread 19 of 28 - Pages(32, 13) 3/20/12 5:19 PM Box D: SPARK Team 2: Barry Coller, MD, Vice President for Medical Affairs and SPARK is designed to transform the discoveries that Stanford University investigators make in Physician-in-Chief, The Rockefeller University their laboratories into pragmatic applications for human health. Although the university’s scientists F. Nina Papavasiliou, PhD, Associate Professor and Head of already are identifying new chemical entities and drug targets with therapeutic applications, these the Laboratory of Lymphocyte Biology, The Rockefeller University discoveries are unlikely to be suffi ciently advanced to attract industry interest. SPARK provides funding, Thomas Tuschl, PhD, Associate Professor and infrastructure, and expertise to move this research toward the clinical stage. Head of the Laboratory for RNA Molecular Biology, The Rockefeller University SPARK fellows are selected on a competitive basis from the pool of investigators who have already Leslie Vosshall, PhD, Robin Chemers Neustein Professor disclosed their inventions to the university’s Offi ce of Technology Licensing. In addition to funding, and Head of the Laboratory of Neurogenetics and Behavior, fellows receive guidance from professionals in academia and industry who provide expertise on the The Rockefeller University many facets of translational science, including protocol development, trial design, intellectual property Team 3: David Skorton, MD, President, Cornell University law, consent form design, and regulatory document submission. It also helps investigators to access the Dirk Schnappinger, PhD, Associate Professor of Microbiology core facilities needed to advance their research and aims to identify industry partnerships and facilitate and Immunology, Weill Cornell Medical College communication between academic and industrial collaborators. With a broad base of participants, SPARK 6:30-7:00 Reception Great Hall is able to bring new and unique perspectives to projects that may have lost momentum. It can help 7:00-8:00 Dinner and remarks by sponsors Dining Room identify failures that may show potential in seemingly unrelated applications, allowing other participants Michael Rosenblatt, MD, Executive Vice President and to pick up the pieces of another project. Chief Medical Offi cer, Merck & Co., Inc. The program also includes a translational research educational component. Fellows are required to Betsy Myers, PhD, Director, Medical Research Program, Doris Duke Charitable Foundation attend a one-year seminar in which they learn about the discovery and development of drugs and Nancy S. Sung, PhD, Senior Program Offi cer, Burroughs Wellcome Fund diagnostics and receive preparation for careers that link scientifi c investigation with enterprise. Joel Kupersmith, MD, Chief Research and Development Offi cer, Veterans Health Administration Source: http://sparkmed.stanford.edu/ 8:00-9:00 Keynote presentation Auditorium Mary J.C. Hendrix, PhD, Medical Research Institute Council Professor, President and Scientifi c Director, Children’s Memorial Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Rockefeller also has developed support information technology platform that allows for Feinberg School of Medicine systems for translational investigators: it conducting protocols. 9:00-9:05 Closing remarks Auditorium facilitates the development of clinical protocols Rice University is developing a researcher’s Richard Galbraith, MD, PhD by providing expertise in the protection toolbox—a website where everything that is of human subjects, subject recruitment, needed to embark on translational research 9:05-11:00 Networking social Rathskeller compliance with trial registration, and protocol projects can be found. For example, to make monitoring and auditing, among other areas. it easier for investigators to collaborate, Rice The institution employs research nurses trained is creating templates for drafting research in care delivery, and medical personnel are agreements, establishing protocols for sharing available to participate in protocols led by a IRBs, and developing animal care protocols that PhD. Clinical research coordinators, who play would allow the movement of experimental critical roles in regulatory compliance and data subjects and materials between performance integrity, are also available to any scientist who sites. It also is working with area biotechnology needs them, as is a customized, comprehensive companies to build a translational and
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FASEB Translational Research Symposium Public Policy Partnerships with Molecular Regional and State Engaging Basic Scientists in Translational Industry, Academia, Biology Economic Development Government, and Disease Research: Identifying Opportunities, Philanthropy Medicinal Chemisty Overcoming Obstacles Pharmaceutical Chemistry March 24-25, 2011 Integration with Technology Transfer Regulatory Science
Drug Discovery and Development Guidelines Clinician Scientists
March 24, 2011 Underpinning Major Industry Experienced Leveraging Regional University Translational Drug Discovery and Drug Development 1:00-3:00 pm Registration Great Hall Research Priorities Development Experts Assets 3:00-3:30 Welcome and meeting goals Auditorium Sean B. Carroll, PhD, Vice President for Science Education, Source: Scott Weir, PharmD, PhD, Institute Director, University of Kansas Cancer Center Howard Hughes Medical Institute Richard Galbraith, MD, PhD, Chair, FASEB Translational Research Steering Committee, Associate Dean, Patient Oriented Research, commercial component into the toolbox. expertise in fundamental biology, the molecular The University of Vermont College of Medicine These support systems are critical for helping mechanisms of disease, and the use of animal 3:30-4:30 Remarks from the NIH Director Auditorium basic scientists move their discoveries models. Establishing these collaborations is Francis Collins, MD, PhD, Director, National Institutes of Health through the translational research pipeline to challenging: academic departments tend to 4:30-6:30 What are the benefi ts of engaging basic scientists in Auditorium commercialization. operate in silos, and basic scientists might translational research? not even work on the same campus as clinical Moderator: Paul Dechow, PhD, Professor and Vice-Chair, Department Developing, Establishing, and researchers, limiting interactions that might of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Sustaining Collaborative Research spark translational research projects and making Health Science Center A successful translational research environment it diffi cult to obtain assistance and mentorship. Team 1: Cindy Farach-Carson, PhD, Associate Vice Provost for Research, It can be even more diffi cult for academic and Rice University requires many different people, trained across government researchers to forge relationships Daniel Wagner, PhD, Assistant Professor, many disciplines, working within a structure Department of Biochemistry and Cell Biology, Rice University that promotes interaction between those who with industry partners, because concerns about have clinical understanding of human health perceived or real confl icts of interest can have a and disease and those who have training and chilling effect on collaborations.
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FASEB Report Layout.FINAL.indd Spread 21 of 28 - Pages(30, 15) 3/20/12 5:19 PM Funding organizations and institutions have been working to bring basic and clinical— Conclusion To solve many of the biggest and academic and industrial scientists— Basic science is the foundation of medical advancement. Investigators with a deep understanding challenges in health care, “It is together through investments in translational of fundamental biology and the mechanisms of disease are essential for translating laboratory research resources and infrastructure. NIH’s discoveries into new and improved health interventions, diagnostics, and treatments. Additional absolutely essential…that we have CTSA program has been an important training, resources, and support would enable basic scientists to move their discoveries forward basic scientists working along with driver in encouraging institutions to foster effectively and effi ciently. Although signifi cant strides have been made, more can be done to optimize basic scientists’ participation in translational research. The research community should expand the clinical scientists. And it is these collaborations, and institutions are experimenting with a variety of approaches. translational research training opportunities for basic researchers and trainees; facilitate their access essential that we have the public The University of California, San Francisco, to the funding, equipment, infrastructure, and other resources needed for translation; encourage and the private sectors working for example, is trying to minimize geographic and support collaboration between basic and clinical investigators across research disciplines and distances between academic and industrial sectors; and recognize and reward basic scientists for the contributions that they make to this growing together from the very outset. researchers by co-locating their laboratory space fi eld. Implementing these recommendations will require action by research institutions and funders, If you have a good idea that you as it did in a recently forged partnership with scientifi c publishers, professional societies, and investigators themselves. Scientifi c societies such as want to try to translate…engage Pfi zer. Ensuring that core resources are available FASEB and the many disciplinary societies representing biomedical researchers have a special role to across departments is another strategy. Providing play in advocating for these changes. We hope that this report will serve as a starting point for moving those industry partners as soon access to statistical centers, biorepositories, forward on this important issue. as possible in the process. All or datasets, for example, can foster cross- too often, investigators, whether fertilization. Institutions have started mentoring programs through which basic scientists mentor Acknowledgments they are in government or in clinical researchers or vice versa, while others FASEB’s Translational Research Steering Committee thanks the Burroughs Wellcome Fund, the academia, will wait until they have convened networking events and regular U.S. Department of Veterans Affairs, the Doris Duke Charitable Foundation, the Howard Hughes seminars or workshops that bring diverse Medical Institute (HHMI), and Merck Sharp & Dohme Corp for their generous support of this have a solidifi ed plan, a strategy, disciplines together. Some academic medical initiative. The committee also thanks Christabelle Salmon and the staff at HHMI for meeting and then go seek funding from centers have begun asking basic scientists to coordination; Drs. Barry Coller, Mary C. (Cindy) Farach-Carson, and William Lowe for their the industrial partner. Another give presentations during grand rounds. The thoughtful reviews; Francoise Vermeylen with the Cornell Statistical Consulting Unit for assistance key to creating an environment that facilitates with the survey analyses; and Lawrence Green for photography. equally important mistake is collaboration is to increase exposure to the that industry is looked upon as other research cultures through closer proximity. Importantly, however, fi nances and resources are only potential funders and not needed to spur collaborations once they have scientifi c collaborators. The most been initiated. value industry can offer is unique Training Basic Investigators in expertise.” Translational Research Gail Cassell, PhD, Visiting Professor, There always have been basic scientists who are Department of Global Health and adept at transforming their research discoveries Social Medicine, Harvard Medical School, into clinical advances. But as the pressure to and Vice President of TB Drug Discovery, accelerate the pace of translation builds, so does Infectious Disease Research Institute in Seattle the need for a cadre of basic investigators with the motivation and skills to apply their work directly to the improvement of human health.
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1 FASEB Report w/Covers.FINAL.indd Spread 24 of 30 - Pages(16, 29) 3/26/12 2:35 PM Recommendations for Funding Strategies According to Coller, The Rockefeller University, not generally covered in basic science training there are three skills that translational programs. These may include an understanding Public and private funders of biomedical research play a key role in encouraging investigators must learn. The fi rst is the ability of disciplines such as biostatistics, pharmacology the entry of basic scientists into translational research. Funders provide direct to defi ne a health need with the same precision and toxicology, biomedical informatics, clinical research support, access to research resources and equipment, and support for as a basic science hypothesis. The second is to research design, and regulatory processes. the development of training programs. Funding policies and incentives also understand how to develop an inexpensive, The structure of basic research training at can motivate the institutional changes needed to support basic investigators. robust, high-throughput assay applicable some institutions may itself present a barrier Together, organizations that support translational research have a wealth of to humans. The third skill is to be able to to acquiring the requisite knowledge and information about the effi cacy of various programs and policies that could be conceptualize a pathway to regulatory approval skills. Translational research is best conducted used to optimize the enterprise going forward. or clinical adoption. Although signifi cant strides by interdisciplinary research teams. Basic have been made in developing translational biomedical science graduate students, however, To attract basic scientists to translational research, it is recommended research training programs that teach these typically choose a discipline, a department, and that funding agencies: and other relevant skills, inadequate experiential even a research topic early in their education. • Recognize milestone and outcome-driven projects as well as those aimed at and didactic training remain a barrier for many They generally are trained on research grants open-ended inquiry when making funding decisions. basic investigators. that support the work of a small area of biology, Whereas clinical examples are integrated and their training is designed to prepare them • Fund translational research projects that engage investigators across disciplines. into the basic science coursework many medical for a career in individual investigator-initiated • Provide supplements to basic research grants that allow investigators to extend students are required to take, graduate students research in a very narrow fi eld. Thus, not only basic research fi ndings into the translational research domain. Similarly, in basic research programs typically are not may the concept of team-based, interdisciplinary provide supplements to clinical investigators to conduct laboratory work based exposed to clinical cases. Furthermore, doctoral research feel foreign to them, but also they on clinical fi ndings. students often do not receive instruction in may not have the training to pursue such • Provide sustained support for translational research infrastructure, pathobiology and pathophysiology, which are collaborations successfully. commercialization centers, and research training programs. key to understanding the mechanisms of disease Narrowly focused training is not unique and the disease relevance of their work. Indeed, to basic investigators. While basic science • Sponsor meetings and other activities to bring groups of researchers together Farach-Carson of Rice University noted that education may not prepare trainees to pursue to interact and learn from one another. graduate students have less contact with basic the medical applications of their discoveries, • Evaluate the outcomes of translational research programs/mechanisms across concepts of medicine than in the past. Another medical education tends not to require suffi cient the enterprise to identify and replicate the programs that are working. participant noted that “trainees frequently competency in basic science research to allow are more knowledgeable about molecules and the physician to recognize or facilitate the • Fund access to core facilities and other resources and advertise these resources structural biology than about the systems application of scientifi c discoveries to medical to the basic science community. in which they function.” These limitations, or public health practice. One panelist noted • Ensure that grant application review panels have the appropriate expertise to combined with little to no opportunity to that medical students typically are not told review translational research projects fairly. This may include creating separate interact with clinical researchers or patient how they can be a part of the discovery process. translational research review groups or study sections and/or ensuring that populations, mean that many basic scientists Communication and collaboration among basic translational researchers are among the scientists represented in review groups. may not think about the science that they do investigators, physician-scientists, and clinical in the context of human health and disease, practitioners are key to advancing translation, and they may not appreciate the unmet clinical and more should be done to bridge this gap needs or the clinical context in which potential during training. interventions would operate. In addition, Biomedical research funding organizations depending on an investigator’s area of interest recognize that this divide exists, and some and his or her particular research, there may be have stepped in to help close it. HHMI’s Med a need to develop familiarity with topics that are into Grad initiative supports and encourages
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FASEB Report Layout.FINAL.indd Spread 23 of 28 - Pages(28, 17) 3/20/12 5:19 PM graduate schools to integrate medical knowledge scientist throughout their graduate training. Recommendations to Recognize and into their doctoral training. The program’s goal The clinical mentor interacts with students in is to produce researchers who will recognize clinics, inpatient hospital rounds, and medical Reward Translational Scientists which biological problems are of the greatest or research conferences where students observe Incentives are needed to encourage and support basic scientists interested in clinical relevance, have the knowledge and skills clinical care and observe or participate in clinical pursuing translational research. Institutional retention, promotion, and tenure necessary to facilitate the translation of new research. The clinical mentor also is a member policies and publishing policies should be modifi ed to ensure that investigators biological knowledge into tools to improve of the thesis committee and in many cases are recognized and rewarded for the contributions that they make to translational human health, and be able to create fruitful helps design a translational aim of the student’s science. research partnerships with physicians. To do research project. This program, like many this, HHMI has awarded 36 four-year grants others sponsored by HHMI, trains PhDs to be It is recommended that institutions: totaling $26 million to institutions offering a effective translational researchers and has forged • Enable investigators to contribute to basic, clinical, and translational science doctoral degree in basic biomedical sciences. numerous collaborations between participating and recognize that evaluation in different areas may require enlisting the These awards have been used to enhance PhD and MD faculty. expertise of faculty from other than the investigator’s primary department. existing graduate programs and initiate new ones. NIH’s CTSA program also is beginning to • Ensure that promotion and tenure guidelines are clear with regard to how Recognizing that there are multiple ways to shape translational research training of basic investigators will be evaluated for contributions they make to interdisciplinary achieve its goal, HHMI has allowed institutions biomedical science investigators. Institutions and team research. the fl exibility to decide what educational receiving CTSA funding are expected to components to include and how their programs provide research, education, training, and • Carefully consider the composition of tenure review committees so that will be structured. For example, Mary Estes, career development in clinical and translational nontraditional—but still rigorous—scholarship is recognized. PhD, Professor, Department of Molecular sciences. With funding from the program, • Consider extending the tenure clock to accommodate scientists involved in Virology and Microbiology, Baylor College of The Rockefeller University initiated a master’s translational studies involving human subjects, which often take longer to Medicine, described how her institution has program in clinical and translational science. complete and publish than studies that do not involve human subjects. put its Med into Grad award to use. Baylor’s It also has developed a one-year certifi cate • Consider the impact of a basic investigator’s work, not just the quality or Translational Biology and Molecular Medicine program to provide basic science trainees with quantity of publications, when evaluating his or her publication records. Graduate program provides doctoral students an introduction to the principles and practice with rigorous training in the basic biomedical of clinical and translational research and the It is recommended that scientifi c publishers and editors: sciences that prepares them for participation opportunity to develop a translational research • Ensure that the roles of authors are clearly articulated in publications. in clinical and translational research. Course protocol. In addition to developing their own • Highlight the potential contributions of basic research fi ndings to public work includes genetics, human physiology, training programs, CTSA institutions have been health by publishing articles or editorials that illustrate the implications a immunology, molecular methods, method working together to develop best practices for particular fi nding has for translation. and logic of translational research, cellular and clinical and translational research training. For molecular biology of disease, gene regulation, instance, the CTSA consortium created a set • Encourage high-impact journals to embrace translational studies (with the animal models, pathophysiology, biostatistics of core competencies that includes 14 thematic caveat that there is still a need for specialty journals that focus on translational for translational research, ethics, conduct and areas that should shape the training experiences research). practical aspects of clinical research, and a of junior investigators. The competencies defi ne It is recommended that individual scientists: bench-to-beside journal club. In the second the skills, attributes, and knowledge needed for year, students embark on their thesis research this type of research and can serve as a guide • Be aware of tenure expectations, clearly articulate their career goals, and and begin clinical project training targeted for anyone considering the development of a negotiate department concurrence. They should defi ne the intellectual space at specifi c areas, including cancer, digestive translational curriculum at multiple graduate or spaces in which they are going to be leaders, especially if translational system disorders, infectious disease, and levels. science is to be important in achieving tenure. reproductive disorders. They also receive dual Although national award competitions • Seek reviewers who understand and value the contributions they make to mentorship by a basic scientist and a clinical have catalyzed the establishment of training translational research when soliciting tenure review letters.
18 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 27
FASEB Report Layout.FINAL.indd Spread 24 of 28 - Pages(18, 27) 3/20/12 5:19 PM It is recommended that individual It is recommended that institutions, programs, some institutions, recognizing the students have been established at MD Anderson scientists: funders, and professional societies: value of translational science, have embarked Cancer Center and The Ohio State University. on their own initiatives. The MD Anderson • Learn to defi ne a health problem with the • Facilitate interaction and collaboration Cancer Center’s Translational Research in Availability and Types of Funding same precision as a basic science hypothesis. among basic and clinical scientists and Multi-Disciplinary Program (TRIUMPH), Many of the translational research success stories clinicians and across sectors and disciplines, • Actively seek and be open to the perspectives for example, is unique in its focus on training described during the meeting had one thing including among researchers in the life and of scientists from different disciplines. postdoctoral-level scientists (see Box E). in common—a component that involved the physical sciences and mathematics through a In addition to providing training at the creative piecing together of resources from many • Seek opportunities and funding to variety of approaches, including: acquire translational research training and graduate and postgraduate level, some meeting places. Despite national efforts to encourage • Creating training and funding mechanisms mentorship, including through course participants suggested that it may be useful to translational science, some meeting participants that encourage interdisciplinary or work, seminars, and workshops; rotations open the possibilities of translational research to lamented the lack of support for individual multisector partnerships. in or collaborations with clinical research undergraduates and even high school students. investigator-initiated projects in this area. And, laboratories; and participation in clinical • Establishing or supporting seminars This may present a unique opportunity, because while making a move to translational research experiences. and workshops as well as networking students at these levels might more readily can open up new funding streams for some opportunities (e.g., research “speed embrace translational research as a career path, basic scientists, others fi nd themselves at a It is recommended that institutions, dating”) that bring scientists and clinicians not yet having formed narrower conceptions of disadvantage in applying for grants to support funding organizations, and professional from different disciplines and sectors their future careers. Baylor, for example, offers a that work. They note that study sections do together. summer program for undergraduates, in which not always have the expertise appropriate for societies work together to: • Creating databases that facilitate the students may work in translational research. reviewing translational protocols. Reviewers • Establish and/or facilitate the establishment identifi cation of potential collaborators. Estes pointed out that several of the students may not appreciate the merits of applied or of summer research experiences for high in its Translational Biology and Molecular translational work, and they may be more • Facilitate access to the research and school and undergraduate students that Medicine Graduate Program initially were sensitive to the strengths of basic, hypothesis- development resources and tools that basic provide exposure to translational research. exposed to translational science through that driven proposals. Moreover, investigators who scientists need to conduct translational program. Similar programs for undergraduate are able to acquire funding note that it is often research. For example, Recommendations to • Institutions and funders should support centers or programs that provide Promote Access to translational research services, including Box E: TRIUMPH—Focus on a New Type of Postdoctoral Experience Translational Research clinical support and expertise in developing technology transfer and data Khandan Keyomarsi, PhD, Professor of Experimental Radiation Oncology, Collaborators and sharing agreements, writing IRB protocols, The University of Texas MD Anderson Cancer Center, described the recruiting patients, and executing clinical university’s Translational Research in Multi-Disciplinary Program (TRIUMPH), Resources trials. a postdoctoral fellowship program that provides training in clinical and If basic investigators are to play a meaningful • Professional societies should publicize translational research for PhD-trained individuals. The immediate goal of role in translating their discoveries into health the availability of national resources and this three-year certifi cate program is to recruit talented, productive, well- applications, then they must have opportunities funding opportunities and provide training trained PhDs and train them through didactic coursework and clinical to interact with clinical investigators, clinicians, and information to help members compete rotations. During the fi rst year, the fellows participate in a series of clinical and industry partners as well as investigators successfully for these opportunities. courses and in fi ve different clinical rotations while pursuing research in from other disciplines. They also need access a translational research laboratory. The program also includes mentorship to the tools and resources necessary to conduct in clinical and translational research and is aimed at producing investigators who can be paired with translational science. physician scientists to lead a translational research laboratory.
26 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 19
FASEB Report Layout.FINAL.indd Spread 25 of 28 - Pages(26, 19) 3/20/12 5:19 PM insuffi cient to cover the full cost of a project. At least one presenter reported that Recommendations to • Facilitate training in the wide range of he had to siphon money away from existing projects to support this work. disciplines and skills needed to conduct Mechanisms of support for trainees may not be optimal for encouraging the Promote Interest, translational research effectively. pursuit of translational research projects. Although there are programs designed to provide training in translation, as described earlier, these opportunities are Education, and Training It is recommended that professional limited. The vast majority of postdoctoral fellows supported by NIH are funded in Translational Science societies: through individual investigator-initiated grants, and they are required to focus on the research for which the grant was awarded. This limits opportunities to The fi rst steps in facilitating the participation • Explore a variety of approaches to spark expand their projects into the translational space or to work on collaborative of basic scientists in translational research are interest, education, and training in projects that may ultimately spark new research directions. It also may create a to spark their interest in advancing the health translational research through professional certain amount of tunnel vision with regard to their research interests. applications of their work and help them meetings and other activities, including: Research funders have taken different approaches to supporting the cultivate their ability to do so. High school • Highlighting translational research at participation of basic scientists in translational research. In addition to its and undergraduate students should be made meetings by calling out these sessions investigator-initiated research grant mechanisms, NIH provides funding through aware of potential career paths in translation, in meeting materials or creating a targeted programs to encourage research in specifi c areas of translation. Its interested graduate and postdoctoral scientists translational research track for poster CTSA program, while not providing direct support to scientists, has catalyzed should be engaged early in their careers, and presentations and talks. institutional efforts to engage and support basic investigators and trainees. The all investigators should have opportunities • Establishing networking opportunities for agency also has mechanisms to provide investigators with access to translational to acquire relevant experiential and didactic basic and clinical investigators and trainees research resources and equipment. The U.S. Department of Veterans Affairs has a training. with similar research interests. small intramural research program. Although about 60 percent of its investigators It is recommended that institutions: • Offering workshops that provide basic are clinicians, it supports a fair number of basic investigators and has the and clinical scientists and trainees with fl exibility to convene teams of basic and clinical scientists around translational • Provide didactic coursework, case-based perspectives on translational research and research projects. learning, and seminars that cover a variety practical tools for establishing translational Private support is more limited, but it does exist. Some foundations support of disease topics and clinical issues. research programs. basic investigators conducting fundamental research in areas relevant to a disease • Incorporate pathobiology and patho- • Providing information about translational for which they want to provide research funding. Other organizations are less physiology courses into basic science research training and career opportunities interested in funding a particular project than they are an investigator who is training programs—fi elds that are especially to students at scientifi c meetings, including likely to make an impact. HHMI’s investigator program, for example, focuses important foundations for understanding student-oriented meetings. on “people not projects,” said Dennis McKearin, PhD, HHMI Senior Scientifi c human health and disease processes. Offi cer. “By giving basic investigators fl exible budgets large enough to explore • Provide opportunities and release time for It is recommended that funding new areas [and] with low administrative burdens,” they have the ability to move basic scientists and trainees to acquire clinical organizations: good ideas from the bench to the bedside. Participants generally agreed that a experiences that will help put basic research diversity of approaches, including support for infrastructure and investigators • Establish and evaluate translational research in context. This can include opportunities for and for targeted and open-ended research, would be important to engaging basic training mechanisms for basic investigators basic scientists to participate in ward rounds; investigators and advancing bench-to-bedside translation. and trainees. attend clinics; observe clinical procedures, Lack of Recognition and Incentives autopsies, and surgeries; and/or take • Encourage and support the mentoring of minisabbaticals to acquire extended training basic scientists and trainees in translational Academic tenure and promotion policies are one area in which incentives may in and understanding of the experimental research, including mentoring by clinical and not be optimal for encouraging basic investigators to develop a translational paradigms possible in humans. translational scientists and by clinicians. research program. Tenure-track faculty are required to bring in research funding and make an identifi able intellectual contribution to their fi elds to gain tenure and promotions, and these contributions are usually measured in research grants
20 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 25
FASEB Report Layout.FINAL.indd Spread 26 of 28 - Pages(20, 25) 3/20/12 5:19 PM Recommendations and publications. Moving a discovery through hypothesis-driven basic science, making it the translational research pipeline often involves diffi cult to publish translational research. team science that may require as many as 30 Moreover, journals may not have a mechanism or 40 collaborators. Tenure, promotion, and to acknowledge the contributions that each There is much that investigators, institutions, professional societies, publishers, and funding institutions can do to support and facilitate the involvement appointment committees are challenged to member of a research team makes to the of basic scientists in translational research: creating more training evaluate the importance and impact of the published work. Although journals devoted opportunities, reforming recognition and reward policies, fostering individual contribution a single faculty member to translational research may address these collaborations, and providing diverse and fl exible forms of fi nancial makes in the context of a multi-investigator concerns, only a few of them exist. support will help. (See Appendix 3 for a list of resources.) But in translational project. The existing paradigms Many of the concerns cited by meeting addition to creating optimal research and training environments, used to evaluate basic science faculty, including participants were echoed by respondents to we must ensure that there are basic investigators who want to pursue numbers of grants and publications, are not FASEB’s translational research survey. (See translational science. The research community should explore ways to always suffi cient to capture the merits of faculty survey insert, page 22.) More than 50 percent spark interest in translation among trainees and established investigators contributions to the translational research of survey respondents found it diffi cult to who may not have considered how they could apply their own interest and enterprise. obtain suffi cient funding for translational expertise in basic biological science to meet public health needs. All of these Tenure and promotion committees also may research, navigate human subjects protections efforts will require leaders who are willing to take risks, create new funding undervalue the contributions of scientists who regulations, obtain the skills necessary for models and reward systems, and provide enhanced environments for science bring technological expertise to collaborations— developing drugs and devices, and access clinical education, training, and collaboration. such as mass spectrometry experts—even if samples. Obtaining didactic and experiential that technology was key to the experiments and training, being recognized for team-based Overarching Recommendations resulting publications. Moreover, compared to research, earning tenure and promotions, as basic science studies, it often takes longer to well as communicating across disciplines and • Funding agencies should continue to support basic science and ensure a bring clinical and translational research projects identifying collaborators also were cited by deep and broad reservoir of new knowledge from which translational research to fruition, resulting in a longer duration many respondents as being diffi cult. can fl ourish. between publications, which may disadvantage The survey also revealed that translational • Additional funding should be provided for both individual and team-based faculty during their evaluations. This problem investigators found it less diffi cult to overcome investigator-initiated translational research grants, beyond the support for is magnifi ed by a lack of understanding of certain barriers than respondents who had not translational research infrastructure currently available. translational science that can prevail among participated in translational research perceived • Institutions, scientifi c publishers, professional societies, and individual multicollegiate faculty serving on tenure it to be. Compared to respondents without scientists should encourage and facilitate a “cultural shift” toward greater committees in university senates when clear translational research experience, translational collaboration, cooperation, communication, and respect among basic and guidelines for evaluating collaborative and/or investigators found it less diffi cult to obtain clinical scientists. The unique roles of both clinical and basic scientists in translational research are absent or marginalized. clinical samples and other necessary resources; translational research must be valued and their contributions to each other’s Recognizing the shift toward team-based, obtain guidance, mentorship, skills, and research programs recognized, and this commensal approach must be modeled interdisciplinary, translational science, some training; identify collaborators; and identify the for the next generation of scientists. institutions have started to explore changes health relevance of their research. It may be that • Institutions should examine promotion and tenure processes to ensure that the in their tenure and promotions policies and establishing a translational research program expectations of basic and clinical scientists engaged in translational research processes to ensure that investigators are is less diffi cult than investigators perceive it are clearly articulated and that their research contributions are quantifi ed, recognized for their research contributions. to be or that those who encounter diffi culties evaluated, and recognized relative to the established expectations. Adding to these diffi culties are challenges ultimately decide not to pursue this line of • Institutions and professional societies should provide environments and scientists face in publishing their translational inquiry. Whatever the explanation, reducing opportunities that facilitate interactions between basic and clinical researchers work. Like study sections and basic science the barriers will likely encourage more basic to spark collaborative activities that will expedite the translation of discoveries promotion committees, editorial boards scientists to explore the translational potential of to application. and reviewers may place a higher value on their work.
24 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 21
FASEB Report Layout.FINAL.indd Spread 27 of 28 - Pages(24, 21) 3/20/12 5:19 PM FASEB Translational Research Survey Why did they get involved in translational research? FASEB conducted a survey of a sample of its societies’ members and meeting attendees to assess scientists’ interest and participation in translational research, as well as the actual and perceived challenges of conducting Impact a disease or a condition translational science. The survey garnered 1,770 complete responses. Impact human health in general
Who responded? Opportunities to collaborate PhD MD/PhD MD Degree Tenure Status Career Stage Opportunities for additional funding 70% 50% 60% 60% Respondents could 40% 50% check more than Research lent itself well to translation 50% 40% one category 40% 30% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 30% 30% 20% 20% 20% 10% 10% 10% What challenges did they face? 0% 0% 0% PhD MD MD/PhD Other TenuredTenure Neither Not Respondents were asked to rate how diffi cult it was to overcome barriers to conducting translational research on track applicable Trainee Other *MD includes all clinical doctorate a scale of 1(not at all diffi cult) through 7 (extremely diffi cult). The top graph shows the ratings for all participants, degrees (e.g., DVM, DDS, OD) Senior scientist Professional staff Early career scientistDept. head/Div.Executive/Sr. chief Admin. whether they had conducted translational research (actual barriers, A) or had not conducted translational research (perceived barriers, P). The bottom graph shows only the challenges that were rated differently by the two groups Organizational Affiliation Research Participation based on Chi Square analysis, p<.05. Not difficult (1-3) Neutral (4) Difficult (5-7) Ever engaged in Ever engaged in biomedical research? translational research? Obtain sufficient funding Navigate human subjects regulations Obtain drug/device development skills 84% Obtain clinical samples No (6%) No (46%) Obtain guidance or mentorship Access necessary resources Yes (94%) Yes (54%) Academic institution Pharma/biotech/CRO Acquire hands-on skills Government agency Scientific/professional society Receive recognition for team work Private organization Other Obtain didactic training Obtain tenure/promotions Communicate across disciplines How did they describe their research programs? Identify collaborators Identify health relevance of research Studies of fundamental biological principles 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Mechanistic studies in cells or cell lines Obtain clinical samples P Mechanistic studies in animals A Obtain guidance or mentorship P Mechanistic studies in humans A P Studies on ex vivo human samples Access necessary resources A First in human studies Acquire hands-on skills P A Lab studies based on human observations Obtain didactic training P A Proof of efficacy studies Identify collaborators P Proof of effectiveness studies PhD MD/PhD MD A Receive recognition for team work P Adoption of best practices A Identify health relevance of research P Other A 0% 10% 20% 30% 40% 50% 60% 70% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
22 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 23
FASEB Report Layout.FINAL.indd Spread 28 of 28 - Pages(22, 23) 3/20/12 5:19 PM FASEB Translational Research Survey Why did they get involved in translational research? FASEB conducted a survey of a sample of its societies’ members and meeting attendees to assess scientists’ interest and participation in translational research, as well as the actual and perceived challenges of conducting Impact a disease or a condition translational science. The survey garnered 1,770 complete responses. Impact human health in general
Who responded? Opportunities to collaborate PhD MD/PhD MD Degree Tenure Status Career Stage Opportunities for additional funding 70% 50% 60% 60% Respondents could 40% 50% check more than Research lent itself well to translation 50% 40% one category 40% 30% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 30% 30% 20% 20% 20% 10% 10% 10% What challenges did they face? 0% 0% 0% PhD MD MD/PhD Other TenuredTenure Neither Not Respondents were asked to rate how diffi cult it was to overcome barriers to conducting translational research on track applicable Trainee Other *MD includes all clinical doctorate a scale of 1(not at all diffi cult) through 7 (extremely diffi cult). The top graph shows the ratings for all participants, degrees (e.g., DVM, DDS, OD) Senior scientist Professional staff Early career scientistDept. head/Div.Executive/Sr. chief Admin. whether they had conducted translational research (actual barriers, A) or had not conducted translational research (perceived barriers, P). The bottom graph shows only the challenges that were rated differently by the two groups Organizational Affiliation Research Participation based on Chi Square analysis, p<.05. Not difficult (1-3) Neutral (4) Difficult (5-7) Ever engaged in Ever engaged in biomedical research? translational research? Obtain sufficient funding Navigate human subjects regulations Obtain drug/device development skills 84% Obtain clinical samples No (6%) No (46%) Obtain guidance or mentorship Access necessary resources Yes (94%) Yes (54%) Academic institution Pharma/biotech/CRO Acquire hands-on skills Government agency Scientific/professional society Receive recognition for team work Private organization Other Obtain didactic training Obtain tenure/promotions Communicate across disciplines How did they describe their research programs? Identify collaborators Identify health relevance of research Studies of fundamental biological principles 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Mechanistic studies in cells or cell lines Obtain clinical samples P Mechanistic studies in animals A Obtain guidance or mentorship P Mechanistic studies in humans A P Studies on ex vivo human samples Access necessary resources A First in human studies Acquire hands-on skills P A Lab studies based on human observations Obtain didactic training P A Proof of efficacy studies Identify collaborators P Proof of effectiveness studies PhD MD/PhD MD A Receive recognition for team work P Adoption of best practices A Identify health relevance of research P Other A 0% 10% 20% 30% 40% 50% 60% 70% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
22 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 23
FASEB Report Layout.FINAL.indd Spread 28 of 28 - Pages(22, 23) 3/20/12 5:19 PM Recommendations and publications. Moving a discovery through hypothesis-driven basic science, making it the translational research pipeline often involves diffi cult to publish translational research. team science that may require as many as 30 Moreover, journals may not have a mechanism or 40 collaborators. Tenure, promotion, and to acknowledge the contributions that each There is much that investigators, institutions, professional societies, publishers, and funding institutions can do to support and facilitate the involvement appointment committees are challenged to member of a research team makes to the of basic scientists in translational research: creating more training evaluate the importance and impact of the published work. Although journals devoted opportunities, reforming recognition and reward policies, fostering individual contribution a single faculty member to translational research may address these collaborations, and providing diverse and fl exible forms of fi nancial makes in the context of a multi-investigator concerns, only a few of them exist. support will help. (See Appendix 3 for a list of resources.) But in translational project. The existing paradigms Many of the concerns cited by meeting addition to creating optimal research and training environments, used to evaluate basic science faculty, including participants were echoed by respondents to we must ensure that there are basic investigators who want to pursue numbers of grants and publications, are not FASEB’s translational research survey. (See translational science. The research community should explore ways to always suffi cient to capture the merits of faculty survey insert, page 22.) More than 50 percent spark interest in translation among trainees and established investigators contributions to the translational research of survey respondents found it diffi cult to who may not have considered how they could apply their own interest and enterprise. obtain suffi cient funding for translational expertise in basic biological science to meet public health needs. All of these Tenure and promotion committees also may research, navigate human subjects protections efforts will require leaders who are willing to take risks, create new funding undervalue the contributions of scientists who regulations, obtain the skills necessary for models and reward systems, and provide enhanced environments for science bring technological expertise to collaborations— developing drugs and devices, and access clinical education, training, and collaboration. such as mass spectrometry experts—even if samples. Obtaining didactic and experiential that technology was key to the experiments and training, being recognized for team-based Overarching Recommendations resulting publications. Moreover, compared to research, earning tenure and promotions, as basic science studies, it often takes longer to well as communicating across disciplines and • Funding agencies should continue to support basic science and ensure a bring clinical and translational research projects identifying collaborators also were cited by deep and broad reservoir of new knowledge from which translational research to fruition, resulting in a longer duration many respondents as being diffi cult. can fl ourish. between publications, which may disadvantage The survey also revealed that translational • Additional funding should be provided for both individual and team-based faculty during their evaluations. This problem investigators found it less diffi cult to overcome investigator-initiated translational research grants, beyond the support for is magnifi ed by a lack of understanding of certain barriers than respondents who had not translational research infrastructure currently available. translational science that can prevail among participated in translational research perceived • Institutions, scientifi c publishers, professional societies, and individual multicollegiate faculty serving on tenure it to be. Compared to respondents without scientists should encourage and facilitate a “cultural shift” toward greater committees in university senates when clear translational research experience, translational collaboration, cooperation, communication, and respect among basic and guidelines for evaluating collaborative and/or investigators found it less diffi cult to obtain clinical scientists. The unique roles of both clinical and basic scientists in translational research are absent or marginalized. clinical samples and other necessary resources; translational research must be valued and their contributions to each other’s Recognizing the shift toward team-based, obtain guidance, mentorship, skills, and research programs recognized, and this commensal approach must be modeled interdisciplinary, translational science, some training; identify collaborators; and identify the for the next generation of scientists. institutions have started to explore changes health relevance of their research. It may be that • Institutions should examine promotion and tenure processes to ensure that the in their tenure and promotions policies and establishing a translational research program expectations of basic and clinical scientists engaged in translational research processes to ensure that investigators are is less diffi cult than investigators perceive it are clearly articulated and that their research contributions are quantifi ed, recognized for their research contributions. to be or that those who encounter diffi culties evaluated, and recognized relative to the established expectations. Adding to these diffi culties are challenges ultimately decide not to pursue this line of • Institutions and professional societies should provide environments and scientists face in publishing their translational inquiry. Whatever the explanation, reducing opportunities that facilitate interactions between basic and clinical researchers work. Like study sections and basic science the barriers will likely encourage more basic to spark collaborative activities that will expedite the translation of discoveries promotion committees, editorial boards scientists to explore the translational potential of to application. and reviewers may place a higher value on their work.
24 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 21
FASEB Report Layout.FINAL.indd Spread 27 of 28 - Pages(24, 21) 3/20/12 5:19 PM insuffi cient to cover the full cost of a project. At least one presenter reported that Recommendations to • Facilitate training in the wide range of he had to siphon money away from existing projects to support this work. disciplines and skills needed to conduct Mechanisms of support for trainees may not be optimal for encouraging the Promote Interest, translational research effectively. pursuit of translational research projects. Although there are programs designed to provide training in translation, as described earlier, these opportunities are Education, and Training It is recommended that professional limited. The vast majority of postdoctoral fellows supported by NIH are funded in Translational Science societies: through individual investigator-initiated grants, and they are required to focus on the research for which the grant was awarded. This limits opportunities to The fi rst steps in facilitating the participation • Explore a variety of approaches to spark expand their projects into the translational space or to work on collaborative of basic scientists in translational research are interest, education, and training in projects that may ultimately spark new research directions. It also may create a to spark their interest in advancing the health translational research through professional certain amount of tunnel vision with regard to their research interests. applications of their work and help them meetings and other activities, including: Research funders have taken different approaches to supporting the cultivate their ability to do so. High school • Highlighting translational research at participation of basic scientists in translational research. In addition to its and undergraduate students should be made meetings by calling out these sessions investigator-initiated research grant mechanisms, NIH provides funding through aware of potential career paths in translation, in meeting materials or creating a targeted programs to encourage research in specifi c areas of translation. Its interested graduate and postdoctoral scientists translational research track for poster CTSA program, while not providing direct support to scientists, has catalyzed should be engaged early in their careers, and presentations and talks. institutional efforts to engage and support basic investigators and trainees. The all investigators should have opportunities • Establishing networking opportunities for agency also has mechanisms to provide investigators with access to translational to acquire relevant experiential and didactic basic and clinical investigators and trainees research resources and equipment. The U.S. Department of Veterans Affairs has a training. with similar research interests. small intramural research program. Although about 60 percent of its investigators It is recommended that institutions: • Offering workshops that provide basic are clinicians, it supports a fair number of basic investigators and has the and clinical scientists and trainees with fl exibility to convene teams of basic and clinical scientists around translational • Provide didactic coursework, case-based perspectives on translational research and research projects. learning, and seminars that cover a variety practical tools for establishing translational Private support is more limited, but it does exist. Some foundations support of disease topics and clinical issues. research programs. basic investigators conducting fundamental research in areas relevant to a disease • Incorporate pathobiology and patho- • Providing information about translational for which they want to provide research funding. Other organizations are less physiology courses into basic science research training and career opportunities interested in funding a particular project than they are an investigator who is training programs—fi elds that are especially to students at scientifi c meetings, including likely to make an impact. HHMI’s investigator program, for example, focuses important foundations for understanding student-oriented meetings. on “people not projects,” said Dennis McKearin, PhD, HHMI Senior Scientifi c human health and disease processes. Offi cer. “By giving basic investigators fl exible budgets large enough to explore • Provide opportunities and release time for It is recommended that funding new areas [and] with low administrative burdens,” they have the ability to move basic scientists and trainees to acquire clinical organizations: good ideas from the bench to the bedside. Participants generally agreed that a experiences that will help put basic research diversity of approaches, including support for infrastructure and investigators • Establish and evaluate translational research in context. This can include opportunities for and for targeted and open-ended research, would be important to engaging basic training mechanisms for basic investigators basic scientists to participate in ward rounds; investigators and advancing bench-to-bedside translation. and trainees. attend clinics; observe clinical procedures, Lack of Recognition and Incentives autopsies, and surgeries; and/or take • Encourage and support the mentoring of minisabbaticals to acquire extended training basic scientists and trainees in translational Academic tenure and promotion policies are one area in which incentives may in and understanding of the experimental research, including mentoring by clinical and not be optimal for encouraging basic investigators to develop a translational paradigms possible in humans. translational scientists and by clinicians. research program. Tenure-track faculty are required to bring in research funding and make an identifi able intellectual contribution to their fi elds to gain tenure and promotions, and these contributions are usually measured in research grants
20 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 25
FASEB Report Layout.FINAL.indd Spread 26 of 28 - Pages(20, 25) 3/20/12 5:19 PM It is recommended that individual It is recommended that institutions, programs, some institutions, recognizing the students have been established at MD Anderson scientists: funders, and professional societies: value of translational science, have embarked Cancer Center and The Ohio State University. on their own initiatives. The MD Anderson • Learn to defi ne a health problem with the • Facilitate interaction and collaboration Cancer Center’s Translational Research in Availability and Types of Funding same precision as a basic science hypothesis. among basic and clinical scientists and Multi-Disciplinary Program (TRIUMPH), Many of the translational research success stories clinicians and across sectors and disciplines, • Actively seek and be open to the perspectives for example, is unique in its focus on training described during the meeting had one thing including among researchers in the life and of scientists from different disciplines. postdoctoral-level scientists (see Box E). in common—a component that involved the physical sciences and mathematics through a In addition to providing training at the creative piecing together of resources from many • Seek opportunities and funding to variety of approaches, including: acquire translational research training and graduate and postgraduate level, some meeting places. Despite national efforts to encourage • Creating training and funding mechanisms mentorship, including through course participants suggested that it may be useful to translational science, some meeting participants that encourage interdisciplinary or work, seminars, and workshops; rotations open the possibilities of translational research to lamented the lack of support for individual multisector partnerships. in or collaborations with clinical research undergraduates and even high school students. investigator-initiated projects in this area. And, laboratories; and participation in clinical • Establishing or supporting seminars This may present a unique opportunity, because while making a move to translational research experiences. and workshops as well as networking students at these levels might more readily can open up new funding streams for some opportunities (e.g., research “speed embrace translational research as a career path, basic scientists, others fi nd themselves at a It is recommended that institutions, dating”) that bring scientists and clinicians not yet having formed narrower conceptions of disadvantage in applying for grants to support funding organizations, and professional from different disciplines and sectors their future careers. Baylor, for example, offers a that work. They note that study sections do together. summer program for undergraduates, in which not always have the expertise appropriate for societies work together to: • Creating databases that facilitate the students may work in translational research. reviewing translational protocols. Reviewers • Establish and/or facilitate the establishment identifi cation of potential collaborators. Estes pointed out that several of the students may not appreciate the merits of applied or of summer research experiences for high in its Translational Biology and Molecular translational work, and they may be more • Facilitate access to the research and school and undergraduate students that Medicine Graduate Program initially were sensitive to the strengths of basic, hypothesis- development resources and tools that basic provide exposure to translational research. exposed to translational science through that driven proposals. Moreover, investigators who scientists need to conduct translational program. Similar programs for undergraduate are able to acquire funding note that it is often research. For example, Recommendations to • Institutions and funders should support centers or programs that provide Promote Access to translational research services, including Box E: TRIUMPH—Focus on a New Type of Postdoctoral Experience Translational Research clinical support and expertise in developing technology transfer and data Khandan Keyomarsi, PhD, Professor of Experimental Radiation Oncology, Collaborators and sharing agreements, writing IRB protocols, The University of Texas MD Anderson Cancer Center, described the recruiting patients, and executing clinical university’s Translational Research in Multi-Disciplinary Program (TRIUMPH), Resources trials. a postdoctoral fellowship program that provides training in clinical and If basic investigators are to play a meaningful • Professional societies should publicize translational research for PhD-trained individuals. The immediate goal of role in translating their discoveries into health the availability of national resources and this three-year certifi cate program is to recruit talented, productive, well- applications, then they must have opportunities funding opportunities and provide training trained PhDs and train them through didactic coursework and clinical to interact with clinical investigators, clinicians, and information to help members compete rotations. During the fi rst year, the fellows participate in a series of clinical and industry partners as well as investigators successfully for these opportunities. courses and in fi ve different clinical rotations while pursuing research in from other disciplines. They also need access a translational research laboratory. The program also includes mentorship to the tools and resources necessary to conduct in clinical and translational research and is aimed at producing investigators who can be paired with translational science. physician scientists to lead a translational research laboratory.
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FASEB Report Layout.FINAL.indd Spread 25 of 28 - Pages(26, 19) 3/20/12 5:19 PM graduate schools to integrate medical knowledge scientist throughout their graduate training. Recommendations to Recognize and into their doctoral training. The program’s goal The clinical mentor interacts with students in is to produce researchers who will recognize clinics, inpatient hospital rounds, and medical Reward Translational Scientists which biological problems are of the greatest or research conferences where students observe Incentives are needed to encourage and support basic scientists interested in clinical relevance, have the knowledge and skills clinical care and observe or participate in clinical pursuing translational research. Institutional retention, promotion, and tenure necessary to facilitate the translation of new research. The clinical mentor also is a member policies and publishing policies should be modifi ed to ensure that investigators biological knowledge into tools to improve of the thesis committee and in many cases are recognized and rewarded for the contributions that they make to translational human health, and be able to create fruitful helps design a translational aim of the student’s science. research partnerships with physicians. To do research project. This program, like many this, HHMI has awarded 36 four-year grants others sponsored by HHMI, trains PhDs to be It is recommended that institutions: totaling $26 million to institutions offering a effective translational researchers and has forged • Enable investigators to contribute to basic, clinical, and translational science doctoral degree in basic biomedical sciences. numerous collaborations between participating and recognize that evaluation in different areas may require enlisting the These awards have been used to enhance PhD and MD faculty. expertise of faculty from other than the investigator’s primary department. existing graduate programs and initiate new ones. NIH’s CTSA program also is beginning to • Ensure that promotion and tenure guidelines are clear with regard to how Recognizing that there are multiple ways to shape translational research training of basic investigators will be evaluated for contributions they make to interdisciplinary achieve its goal, HHMI has allowed institutions biomedical science investigators. Institutions and team research. the fl exibility to decide what educational receiving CTSA funding are expected to components to include and how their programs provide research, education, training, and • Carefully consider the composition of tenure review committees so that will be structured. For example, Mary Estes, career development in clinical and translational nontraditional—but still rigorous—scholarship is recognized. PhD, Professor, Department of Molecular sciences. With funding from the program, • Consider extending the tenure clock to accommodate scientists involved in Virology and Microbiology, Baylor College of The Rockefeller University initiated a master’s translational studies involving human subjects, which often take longer to Medicine, described how her institution has program in clinical and translational science. complete and publish than studies that do not involve human subjects. put its Med into Grad award to use. Baylor’s It also has developed a one-year certifi cate • Consider the impact of a basic investigator’s work, not just the quality or Translational Biology and Molecular Medicine program to provide basic science trainees with quantity of publications, when evaluating his or her publication records. Graduate program provides doctoral students an introduction to the principles and practice with rigorous training in the basic biomedical of clinical and translational research and the It is recommended that scientifi c publishers and editors: sciences that prepares them for participation opportunity to develop a translational research • Ensure that the roles of authors are clearly articulated in publications. in clinical and translational research. Course protocol. In addition to developing their own • Highlight the potential contributions of basic research fi ndings to public work includes genetics, human physiology, training programs, CTSA institutions have been health by publishing articles or editorials that illustrate the implications a immunology, molecular methods, method working together to develop best practices for particular fi nding has for translation. and logic of translational research, cellular and clinical and translational research training. For molecular biology of disease, gene regulation, instance, the CTSA consortium created a set • Encourage high-impact journals to embrace translational studies (with the animal models, pathophysiology, biostatistics of core competencies that includes 14 thematic caveat that there is still a need for specialty journals that focus on translational for translational research, ethics, conduct and areas that should shape the training experiences research). practical aspects of clinical research, and a of junior investigators. The competencies defi ne It is recommended that individual scientists: bench-to-beside journal club. In the second the skills, attributes, and knowledge needed for year, students embark on their thesis research this type of research and can serve as a guide • Be aware of tenure expectations, clearly articulate their career goals, and and begin clinical project training targeted for anyone considering the development of a negotiate department concurrence. They should defi ne the intellectual space at specifi c areas, including cancer, digestive translational curriculum at multiple graduate or spaces in which they are going to be leaders, especially if translational system disorders, infectious disease, and levels. science is to be important in achieving tenure. reproductive disorders. They also receive dual Although national award competitions • Seek reviewers who understand and value the contributions they make to mentorship by a basic scientist and a clinical have catalyzed the establishment of training translational research when soliciting tenure review letters.
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FASEB Report Layout.FINAL.indd Spread 24 of 28 - Pages(18, 27) 3/20/12 5:19 PM Recommendations for Funding Strategies According to Coller, The Rockefeller University, not generally covered in basic science training there are three skills that translational programs. These may include an understanding Public and private funders of biomedical research play a key role in encouraging investigators must learn. The fi rst is the ability of disciplines such as biostatistics, pharmacology the entry of basic scientists into translational research. Funders provide direct to defi ne a health need with the same precision and toxicology, biomedical informatics, clinical research support, access to research resources and equipment, and support for as a basic science hypothesis. The second is to research design, and regulatory processes. the development of training programs. Funding policies and incentives also understand how to develop an inexpensive, The structure of basic research training at can motivate the institutional changes needed to support basic investigators. robust, high-throughput assay applicable some institutions may itself present a barrier Together, organizations that support translational research have a wealth of to humans. The third skill is to be able to to acquiring the requisite knowledge and information about the effi cacy of various programs and policies that could be conceptualize a pathway to regulatory approval skills. Translational research is best conducted used to optimize the enterprise going forward. or clinical adoption. Although signifi cant strides by interdisciplinary research teams. Basic have been made in developing translational biomedical science graduate students, however, To attract basic scientists to translational research, it is recommended research training programs that teach these typically choose a discipline, a department, and that funding agencies: and other relevant skills, inadequate experiential even a research topic early in their education. • Recognize milestone and outcome-driven projects as well as those aimed at and didactic training remain a barrier for many They generally are trained on research grants open-ended inquiry when making funding decisions. basic investigators. that support the work of a small area of biology, Whereas clinical examples are integrated and their training is designed to prepare them • Fund translational research projects that engage investigators across disciplines. into the basic science coursework many medical for a career in individual investigator-initiated • Provide supplements to basic research grants that allow investigators to extend students are required to take, graduate students research in a very narrow fi eld. Thus, not only basic research fi ndings into the translational research domain. Similarly, in basic research programs typically are not may the concept of team-based, interdisciplinary provide supplements to clinical investigators to conduct laboratory work based exposed to clinical cases. Furthermore, doctoral research feel foreign to them, but also they on clinical fi ndings. students often do not receive instruction in may not have the training to pursue such • Provide sustained support for translational research infrastructure, pathobiology and pathophysiology, which are collaborations successfully. commercialization centers, and research training programs. key to understanding the mechanisms of disease Narrowly focused training is not unique and the disease relevance of their work. Indeed, to basic investigators. While basic science • Sponsor meetings and other activities to bring groups of researchers together Farach-Carson of Rice University noted that education may not prepare trainees to pursue to interact and learn from one another. graduate students have less contact with basic the medical applications of their discoveries, • Evaluate the outcomes of translational research programs/mechanisms across concepts of medicine than in the past. Another medical education tends not to require suffi cient the enterprise to identify and replicate the programs that are working. participant noted that “trainees frequently competency in basic science research to allow are more knowledgeable about molecules and the physician to recognize or facilitate the • Fund access to core facilities and other resources and advertise these resources structural biology than about the systems application of scientifi c discoveries to medical to the basic science community. in which they function.” These limitations, or public health practice. One panelist noted • Ensure that grant application review panels have the appropriate expertise to combined with little to no opportunity to that medical students typically are not told review translational research projects fairly. This may include creating separate interact with clinical researchers or patient how they can be a part of the discovery process. translational research review groups or study sections and/or ensuring that populations, mean that many basic scientists Communication and collaboration among basic translational researchers are among the scientists represented in review groups. may not think about the science that they do investigators, physician-scientists, and clinical in the context of human health and disease, practitioners are key to advancing translation, and they may not appreciate the unmet clinical and more should be done to bridge this gap needs or the clinical context in which potential during training. interventions would operate. In addition, Biomedical research funding organizations depending on an investigator’s area of interest recognize that this divide exists, and some and his or her particular research, there may be have stepped in to help close it. HHMI’s Med a need to develop familiarity with topics that are into Grad initiative supports and encourages
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FASEB Report Layout.FINAL.indd Spread 23 of 28 - Pages(28, 17) 3/20/12 5:19 PM Funding organizations and institutions have been working to bring basic and clinical— Conclusion To solve many of the biggest and academic and industrial scientists— Basic science is the foundation of medical advancement. Investigators with a deep understanding challenges in health care, “It is together through investments in translational of fundamental biology and the mechanisms of disease are essential for translating laboratory research resources and infrastructure. NIH’s discoveries into new and improved health interventions, diagnostics, and treatments. Additional absolutely essential…that we have CTSA program has been an important training, resources, and support would enable basic scientists to move their discoveries forward basic scientists working along with driver in encouraging institutions to foster effectively and effi ciently. Although signifi cant strides have been made, more can be done to optimize basic scientists’ participation in translational research. The research community should expand the clinical scientists. And it is these collaborations, and institutions are experimenting with a variety of approaches. translational research training opportunities for basic researchers and trainees; facilitate their access essential that we have the public The University of California, San Francisco, to the funding, equipment, infrastructure, and other resources needed for translation; encourage and the private sectors working for example, is trying to minimize geographic and support collaboration between basic and clinical investigators across research disciplines and distances between academic and industrial sectors; and recognize and reward basic scientists for the contributions that they make to this growing together from the very outset. researchers by co-locating their laboratory space fi eld. Implementing these recommendations will require action by research institutions and funders, If you have a good idea that you as it did in a recently forged partnership with scientifi c publishers, professional societies, and investigators themselves. Scientifi c societies such as want to try to translate…engage Pfi zer. Ensuring that core resources are available FASEB and the many disciplinary societies representing biomedical researchers have a special role to across departments is another strategy. Providing play in advocating for these changes. We hope that this report will serve as a starting point for moving those industry partners as soon access to statistical centers, biorepositories, forward on this important issue. as possible in the process. All or datasets, for example, can foster cross- too often, investigators, whether fertilization. Institutions have started mentoring programs through which basic scientists mentor Acknowledgments they are in government or in clinical researchers or vice versa, while others FASEB’s Translational Research Steering Committee thanks the Burroughs Wellcome Fund, the academia, will wait until they have convened networking events and regular U.S. Department of Veterans Affairs, the Doris Duke Charitable Foundation, the Howard Hughes seminars or workshops that bring diverse Medical Institute (HHMI), and Merck Sharp & Dohme Corp for their generous support of this have a solidifi ed plan, a strategy, disciplines together. Some academic medical initiative. The committee also thanks Christabelle Salmon and the staff at HHMI for meeting and then go seek funding from centers have begun asking basic scientists to coordination; Drs. Barry Coller, Mary C. (Cindy) Farach-Carson, and William Lowe for their the industrial partner. Another give presentations during grand rounds. The thoughtful reviews; Francoise Vermeylen with the Cornell Statistical Consulting Unit for assistance key to creating an environment that facilitates with the survey analyses; and Lawrence Green for photography. equally important mistake is collaboration is to increase exposure to the that industry is looked upon as other research cultures through closer proximity. Importantly, however, fi nances and resources are only potential funders and not needed to spur collaborations once they have scientifi c collaborators. The most been initiated. value industry can offer is unique Training Basic Investigators in expertise.” Translational Research Gail Cassell, PhD, Visiting Professor, There always have been basic scientists who are Department of Global Health and adept at transforming their research discoveries Social Medicine, Harvard Medical School, into clinical advances. But as the pressure to and Vice President of TB Drug Discovery, accelerate the pace of translation builds, so does Infectious Disease Research Institute in Seattle the need for a cadre of basic investigators with the motivation and skills to apply their work directly to the improvement of human health.
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1 FASEB Report w/Covers.FINAL.indd Spread 24 of 30 - Pages(16, 29) 3/26/12 2:35 PM Appendix 1: Agenda Figure 1: Translational Research “Village”
FASEB Translational Research Symposium Public Policy Partnerships with Molecular Regional and State Engaging Basic Scientists in Translational Industry, Academia, Biology Economic Development Government, and Disease Research: Identifying Opportunities, Philanthropy Medicinal Chemisty Overcoming Obstacles Pharmaceutical Chemistry March 24-25, 2011 Integration with Technology Transfer Regulatory Science
Drug Discovery and Development Guidelines Clinician Scientists
March 24, 2011 Underpinning Major Industry Experienced Leveraging Regional University Translational Drug Discovery and Drug Development 1:00-3:00 pm Registration Great Hall Research Priorities Development Experts Assets 3:00-3:30 Welcome and meeting goals Auditorium Sean B. Carroll, PhD, Vice President for Science Education, Source: Scott Weir, PharmD, PhD, Institute Director, University of Kansas Cancer Center Howard Hughes Medical Institute Richard Galbraith, MD, PhD, Chair, FASEB Translational Research Steering Committee, Associate Dean, Patient Oriented Research, commercial component into the toolbox. expertise in fundamental biology, the molecular The University of Vermont College of Medicine These support systems are critical for helping mechanisms of disease, and the use of animal 3:30-4:30 Remarks from the NIH Director Auditorium basic scientists move their discoveries models. Establishing these collaborations is Francis Collins, MD, PhD, Director, National Institutes of Health through the translational research pipeline to challenging: academic departments tend to 4:30-6:30 What are the benefi ts of engaging basic scientists in Auditorium commercialization. operate in silos, and basic scientists might translational research? not even work on the same campus as clinical Moderator: Paul Dechow, PhD, Professor and Vice-Chair, Department Developing, Establishing, and researchers, limiting interactions that might of Biomedical Sciences, Baylor College of Dentistry, Texas A&M Sustaining Collaborative Research spark translational research projects and making Health Science Center A successful translational research environment it diffi cult to obtain assistance and mentorship. Team 1: Cindy Farach-Carson, PhD, Associate Vice Provost for Research, It can be even more diffi cult for academic and Rice University requires many different people, trained across government researchers to forge relationships Daniel Wagner, PhD, Assistant Professor, many disciplines, working within a structure Department of Biochemistry and Cell Biology, Rice University that promotes interaction between those who with industry partners, because concerns about have clinical understanding of human health perceived or real confl icts of interest can have a and disease and those who have training and chilling effect on collaborations.
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FASEB Report Layout.FINAL.indd Spread 21 of 28 - Pages(30, 15) 3/20/12 5:19 PM Box D: SPARK Team 2: Barry Coller, MD, Vice President for Medical Affairs and SPARK is designed to transform the discoveries that Stanford University investigators make in Physician-in-Chief, The Rockefeller University their laboratories into pragmatic applications for human health. Although the university’s scientists F. Nina Papavasiliou, PhD, Associate Professor and Head of already are identifying new chemical entities and drug targets with therapeutic applications, these the Laboratory of Lymphocyte Biology, The Rockefeller University discoveries are unlikely to be suffi ciently advanced to attract industry interest. SPARK provides funding, Thomas Tuschl, PhD, Associate Professor and infrastructure, and expertise to move this research toward the clinical stage. Head of the Laboratory for RNA Molecular Biology, The Rockefeller University SPARK fellows are selected on a competitive basis from the pool of investigators who have already Leslie Vosshall, PhD, Robin Chemers Neustein Professor disclosed their inventions to the university’s Offi ce of Technology Licensing. In addition to funding, and Head of the Laboratory of Neurogenetics and Behavior, fellows receive guidance from professionals in academia and industry who provide expertise on the The Rockefeller University many facets of translational science, including protocol development, trial design, intellectual property Team 3: David Skorton, MD, President, Cornell University law, consent form design, and regulatory document submission. It also helps investigators to access the Dirk Schnappinger, PhD, Associate Professor of Microbiology core facilities needed to advance their research and aims to identify industry partnerships and facilitate and Immunology, Weill Cornell Medical College communication between academic and industrial collaborators. With a broad base of participants, SPARK 6:30-7:00 Reception Great Hall is able to bring new and unique perspectives to projects that may have lost momentum. It can help 7:00-8:00 Dinner and remarks by sponsors Dining Room identify failures that may show potential in seemingly unrelated applications, allowing other participants Michael Rosenblatt, MD, Executive Vice President and to pick up the pieces of another project. Chief Medical Offi cer, Merck & Co., Inc. The program also includes a translational research educational component. Fellows are required to Betsy Myers, PhD, Director, Medical Research Program, Doris Duke Charitable Foundation attend a one-year seminar in which they learn about the discovery and development of drugs and Nancy S. Sung, PhD, Senior Program Offi cer, Burroughs Wellcome Fund diagnostics and receive preparation for careers that link scientifi c investigation with enterprise. Joel Kupersmith, MD, Chief Research and Development Offi cer, Veterans Health Administration Source: http://sparkmed.stanford.edu/ 8:00-9:00 Keynote presentation Auditorium Mary J.C. Hendrix, PhD, Medical Research Institute Council Professor, President and Scientifi c Director, Children’s Memorial Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Rockefeller also has developed support information technology platform that allows for Feinberg School of Medicine systems for translational investigators: it conducting protocols. 9:00-9:05 Closing remarks Auditorium facilitates the development of clinical protocols Rice University is developing a researcher’s Richard Galbraith, MD, PhD by providing expertise in the protection toolbox—a website where everything that is of human subjects, subject recruitment, needed to embark on translational research 9:05-11:00 Networking social Rathskeller compliance with trial registration, and protocol projects can be found. For example, to make monitoring and auditing, among other areas. it easier for investigators to collaborate, Rice The institution employs research nurses trained is creating templates for drafting research in care delivery, and medical personnel are agreements, establishing protocols for sharing available to participate in protocols led by a IRBs, and developing animal care protocols that PhD. Clinical research coordinators, who play would allow the movement of experimental critical roles in regulatory compliance and data subjects and materials between performance integrity, are also available to any scientist who sites. It also is working with area biotechnology needs them, as is a customized, comprehensive companies to build a translational and
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FASEB Report Layout.FINAL.indd Spread 20 of 28 - Pages(14, 31) 3/20/12 5:19 PM March 25, 2011 Box C: Going It Alone—Sometimes the Translational Scientist
7:30-8:15 am Breakfast Dining Room Is His or Her Own Best Ally 8:15-9:15 Table discussions: Sparking interest in translational research Dining Room Daria Mochly-Rosen, PhD, Professor and Senior Associate Dean for Research and Director of 9:15-11:30 What are the challenges to engaging basic scientists in Auditorium translational research? SPARK, Stanford University’s Translational Research Program, is a protein chemist conducting translational research. Early in her career, she designed rational inhibitors that could turn off Survey results John Smith, MD, PhD, MMM, DSc (Hon), heart cell enzymes one at a time and discovered enzymes that could change the rate at which Professor of Pathology and Director, Division of Laboratory Medicine, heart cells in culture beat. She thought this was an important fi nding that would be of interest University of Alabama at Birmingham to the heart research community, but when she presented her work at a scientifi c meeting, Perspectives across career levels she found the audience to be disinterested in heart rate regulation. Clinicians, she had been Moderator: John Smith, MD, PhD, MMM, DSc (Hon) told, already had ways of managing heart rate; they were concerned with problems such as cardiac ischemia. Panelists: Michael Dyer, PhD, Co-Leader, Developmental Therapeutics for Solid Malignancies Program, St. Jude Children’s Research Hospital Following the advice of a colleague, she invited into her laboratory a physician who wanted Daria Mochly-Rosen, PhD, Professor and Senior Associate Dean to learn basic research and from whom she could learn how to study more clinically relevant for Research and Director of SPARK, Stanford’s Translational Research Program, Stanford University, School of Medicine problems. Her work eventually led to the discovery of an inhibitor that when administered after Philip Haydon, PhD, Annetta and Gustav Grisard Professor and Chair, a heart attack reduces heart damage by 70 percent and prevents subsequent heart failure, Department of Neuroscience, Tufts University School of Medicine a fi nding that was demonstrated in mice, rats, guinea pigs, rabbits, and pigs. Patents were Robert J. Alpern, MD, Ensign Professor of Medicine and Dean, written and the results published. Yet no one was interested in her fi ndings. Why would this Yale School of Medicine not be useful in patients, she thought?
11:30-12:15 pm Lunch Dining Room When she brought her idea directly to industry, company after company turned her away. She 12:15-2:00 Breakout sessions: later realized that there were good reasons for this: while her work was attractive from a basic How can the research community address these challenges? research point of view, the barriers to executing it in patients were huge, and many steps had to be completed before reaching that goal. Mochly-Rosen reached out to her colleagues Breakout 1: Facilitating translational research training Auditorium for assistance, but rather than fi nding support, she was discouraged from pursuing this Moderator: William Galey, PhD, Director, Graduate and Medical Education Programs, Howard Hughes Medical Institute line of inquiry and from working with industry. Translational research, she was told, is not intellectually challenging, worthwhile, or good for her career. “Career progress in academia is Panelists: Khandan Keyomarsi, PhD, Professor, Department measured by how many papers are published and how much grant funding is received rather of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center than, for example, attempting to produce a new drug,” she said. (Initiative: TRIUMPH Postdoctoral Fellowship) But she persevered, formed her own company, KAI Pharmaceuticals, and spent a year as Matthew J. Walter, MD, Assistant Professor of Medicine and Genetics, Washington University School of Medicine its Chief Scientifi c Offi cer. She helped write an Investigational New Drug Application and (Initiative: Lucille P. Markey Special Emphasis Pathway launched a clinical trial. “Unlike my training in academia, where questions led to the research, in Human Pathobiology) in industry I learned to think about the fi nal product and work backwards, to identify what Mary Estes, PhD, Professor, Department of Molecular research needs to support such a product,” said Mochly-Rosen. The process was humbling, Virology and Microbiology, Baylor College of Medicine but also gratifying. “There is nothing more rewarding than [treating] the fi rst patient…or when (Initiative: HHMI Med into Grad) the trial is fi nished, looking at the data. It’s really a true manifestation of what basic research Rebecca Jackson, MD, Professor and Associate Dean, should eventually lead to.” College of Medicine, The Ohio State University (Initiative: CTSA Consortium Training and Career Development of Clinical/Translational Scientists)
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FASEB Report Layout.FINAL.indd Spread 19 of 28 - Pages(32, 13) 3/20/12 5:19 PM Culture and Mindset their work or discuss a particular topic. As a Breakout 2: Facilitating productive collaborations Small Auditorium (K202) Basic scientists may see their controlled, result, people who had no interest in diseases are Moderator: Richard Bockman, MD, PhD, Professor of Medicine, now gaining interest. Haydon has observed that Endocrine Division, Weill Cornell Medical College, hypothesis-driven research as more rigorous and Chief of the Endocrine Service, Hospital for Special Surgery than the goal-directed or descriptive research faculty members who are surrounded by others with a translational focus are more likely to Panelists: Gail Cassell, PhD, Visiting Professor, often conducted with humans in clinical Department of Global Health and Social Medicine, research settings. On the other hand, clinical develop the interests and skills needed to adapt. Harvard Medical School and Vice President of TB Drug Discovery, scientists may view their work as superior Infectious Disease Research Institute in Seattle insofar as it has greater relevance to human Insuffi cient Infrastructure to Scott J. Weir, PharmD, PhD, Director, Institute for Advancing Medical Innovation, University of Kansas Cancer Center health and disease. These perceived differences Develop Clinical Protocols, Facilitate Lee M. Nadler, MD, Virginia and D.K. Ludwig Professor not only inhibit collaborations between the Exchanges, and Enable Handoffs of Medicine, Harvard Medical School two groups, but also they may discourage Many basic scientists (and some clinical Jeffrey Bluestone, PhD, A.W. and Mary Margaret Clausen basic investigators from pursuing translational scientists) fi nd the pathway to clinical Distinguished Professor, Executive Vice Chancellor, and Provost, projects (see Box C). Even when basic scientists application fi lled with unfamiliar requirements University of California, San Francisco are open to translation, they do not necessarily and administrative procedures. Translational Breakout 3: Providing appropriate recognition and rewards D124 speak the same language as their clinical research involving human subjects may Moderator: Patrick Stover, PhD, Professor and Director, investigator counterparts because of differences require IRB and Privacy Board approval, Division of Nutritional Sciences, Cornell University in training and experience. reporting to data safety monitoring boards, Panelists: Sally Kornbluth, PhD, Vice Dean for Research, Institutions where translational research clinical trials registration, and specialized James B. Duke Professor, Pharmacology and Cancer Biology, Duke University School of Medicine fl ourishes have had to focus on overcoming the patient recruitment techniques. Working with cultural differences between basic and clinical Francesco Marincola, MD, Editor-in-Chief, industry adds a level of complexity, because Journal of Translational Medicine and Chief, scientists. They do this by creating opportunities confl ict of interest disclosures and data use Infectious Disease and Immunogenetics Section, for these investigators to share perspectives, see and intellectual property agreements must Department of Transfusion Medicine, the value in each other’s work, and embrace be drafted. As a result, carrying out a clinical National Institutes of Health Clinical Center both hypothesis testing and goal-oriented protocol can require more steps and time than Paul DiCorleto, PhD, The Sherwin-Page Chair, Cleveland Clinic Lerner Research Institute research. Philip Haydon, PhD, Professor and a laboratory-based protocol. Basic investigators Chair, Department of Neuroscience, Tufts usually do not have experience navigating these Breakout 4: The role of funding organizations D125 University School of Medicine, said he was requirements, and their universities may or Moderator: Nancy S. Sung, PhD, Senior Program Offi cer, Burroughs Wellcome Fund brought to Tufts to change the culture. When not have the expertise and infrastructure to he moved into the university’s neuroscience help them. Panelists: Barbara Alving, MD, Director, National Center for Research Resources, department, there was a focus on synaptic Some institutions have been proactive in physiology, but very little of the work had National Institutes of Health addressing these needs (see Box D). The Institute Sally McNagny, MD, MPH, FACP, Vice President, any translational thrust. He was faced with for Advancing Medical Innovation at the The Medical Foundation, a division of HRiA the challenge of identifying translational University of Kansas Cancer Center forms project Joel Kupersmith, MD, Chief Research and Development Offi cer, opportunities for faculty engaged in rigorous, management teams around technologies ripe for Veterans Health Administration basic work and helping to move them along translation. These teams provide investigators Dennis McKearin, PhD, Senior Scientifi c Offi cer, Howard Hughes Medical Institute that path. with the expertise they need in areas such as One way Haydon is trying to do this is drug discovery and development, industrial and 2:00-2:15 Break Great Hall by developing three faculty clusters that act philanthropic partnering, technology transfer, much like magnets. These clusters (in epilepsy, 2:15-3:00 Recommendations from breakout groups Auditorium and medicinal chemistry. This support ensures Breakout session moderators depression, and neurodegeneration) are open to that investigators can focus on their area of trainees, as well as faculty, and they meet every expertise: the science (see Figure 1). 3:00-3:15 Wrap up and next steps Auditorium two to three weeks for lunch to hear talks about Richard Galbraith, MD, PhD
12 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 33
FASEB Report Layout.FINAL.indd Spread 18 of 28 - Pages(12, 33) 3/20/12 5:19 PM Appendix 2: Meeting Participants research competencies and capabilities. In sum, institutions benefi t from Pharmaceutical industry veterans were recruited fostering translational research to establish best practices. In addition to programs by: working with the University of Kansas cancer Myles Akabas, MD, PhD Sanjay Bidichandani, MBBS, PhD biologists, efforts to establish partnerships with • Connecting their investigators to resources Professor of Physiology & Biophysics Vice President for Research and collaborators and facilitating affordable Muscular Dystrophy Association industry, academia, government, and disease Director, Medical Scientist Training Program access to expensive shared equipment and Albert Einstein College of Medicine of Yeshiva University [email protected] philanthropy collaborators were initiated to gain [email protected] facilities. Linda Birnbaum, PhD access to novel drug targets. Robert Alpern, MD Director The university has refi ned its role in cancer • Providing unique training opportunities Dean National Institute of Environmental Health Sciences therapeutics. With a focus on unmet medical for undergraduates, graduate students, and National Institutes of Health Yale School of Medicine needs such as rare and neglected diseases and postdoctorates and encouraging new talent to [email protected] [email protected] pediatrics, it has established translational enter biomedical research. Mitsi Blount, PhD Bruce Altevogt, PhD Assistant Professor research processes to discover and develop novel Senior Program Offi cer • Promoting the development of new drugs, Emory University drugs as well as identify new uses for approved Institute of Medicine devices, and other medical interventions, [email protected] and abandoned drugs. It has integrated and [email protected] which advances their biomedical research even rebuilt core facilities, developed a strategy Jeffrey Bluestone, PhD missions, attracts patients, and enhances their Barbara Alving, MD, MACP Professor, Executive Vice Chancellor, and Provost for handling technology transfer, put proof-of- Director University of California San Francisco status. National Center for Research Resources [email protected] concept funding strategies in place, and formed National Institutes of Health multidisciplinary and multi-organizational • Gaining access to new funding streams [email protected] Richard Bockman, MD, PhD teams managed by industry-experienced project supporting both institutional and individual Professor of Medicine Margaret Anderson, MS Weill Medical College/Hospital for Special Surgery managers. The center also invested heavily in projects. Executive Director [email protected] project managers who oversee all aspects of • Attracting public-private partnerships and FasterCures translation, freeing up investigators to focus [email protected] Jo Boughman, PhD leveraging federal and nonfederal resources. Executive Vice President on the science, and it is looking beyond its James C. Austin, PhD American Society of Human Genetics own walls for promising ideas to move drug [email protected] Editor, Science Careers development forward. AAAS Challenges to Engaging Pamela Bradley, PhD [email protected] By demonstrating successes in translational Associate Director of Science Policy research, the university was able to attract top- Basic Scientists in Robert Berdahl, PhD American Association for Cancer Research President [email protected] notch cancer researchers who are interested Translational Research Association of American Universities Linda Brady, PhD in drug discovery and development. It has [email protected] Director, Division of Neuroscience and Basic Behavioral recruited more than 230 years of pharmaceutical Meeting participants noted that numerous Science challenges can discourage or prevent basic Daniel Bernard, PhD experience over the past fi ve years, from National Institute of Mental Health investigators from participating in translational Associate Professor [email protected] investigators pursuing target validation to those McGill University doing clinical testing. Its collaborations have science. These include differences in culture [email protected] Brian Brewer brought in a broad array of new funding sources and mindset between basic and clinical Director of Communications researchers, insuffi cient and/or nonsupportive Jim Bernstein, MPA Cancer Research Institute to support additional collaborations, including Director [email protected] those involving government and philanthropic infrastructure, diffi culty developing and Government & Public Affairs sustaining collaborations, inadequate training, American Society for Pharmacology & Experimental PJ Brooks, PhD organizations and those related to state Therapeutics Program Offi cer and Adjunct Investigator economic development initiatives. The center insuffi cient funding, and lack of other incentives [email protected] National Institute on Alcohol Abuse and Alcoholism brought three new therapies to the clinic in and rewards. and Offi ce of Rare Diseases Research National Institutes of Health 2009, moved one forward in 2010, and brought [email protected] fi ve more to the clinic in 2011.
34 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 11
FASEB Report Layout.FINAL.indd Spread 17 of 28 - Pages(34, 11) 3/20/12 5:19 PM Scott Campbell, PhD Barry Coller, MD Executive Director and CEO Physician-in-Chief and Vice President for Medical Affairs Foundation for the National Institutes of Health The Rockefeller University [email protected] [email protected]
Maria Teresa Canto, DDS, MS, MPH Francis Collins, MD, PhD Health Scientist Administrator Director National Center for Research Resources National Institutes of Health National Institutes of Health [email protected] [email protected] Angela Colmone, PhD Sean Carroll, PhD Associate Editor Vice President for Science Education Science Translational Medicine Howard Hughes Medical Institute [email protected] [email protected] Leslie Cooper, RN, BSN, MPH, PhD Robert Carter, MD, PhD Program Offi cer Deputy Director National Center for Research Resources National Institute of Arthritis and Musculoskeletal National Institutes of Health and Skin Diseases [email protected] National Institutes of Health [email protected] Milton Corn, MD Deputy Director for Research and Education David Skorton, MD, President, Cornell University and Dirk Schnappinger, PhD, Associate Professor, Weill Cornell Medical College Gail Cassell, PhD National Library of Medicine Visiting Professor National Institutes of Health Department of Global Health and Social Medicine [email protected] Harvard Medical School and In addition to benefi ting their scholars, university, state, and regional priority. The Kyle Covington Vice President of TB Drug Discovery investing in translational research has a positive center’s goal was to capitalize on the strengths Graduate Student Infectious Disease Research Institute in Seattle Baylor College of Medicine impact on institutions as a whole. Fostering an of the university and on regional assets to [email protected] environment conducive to translation advances become a national leader in the discovery and [email protected] John Chatham, PhD the core missions of biomedical research advancement to Phase I of promising anticancer James M. Crawford, MD, PhD Professor and Director Senior Vice President institutions, stated Barry Coller, MD, Vice agents. Molecular and Cellular Pathology Pathology & Laboratory Medicine President for Medical Affairs and Physician- Before the center was started, the University University of Alabama at Birmingham North Shore-Long Island Jewish Health System [email protected] in-Chief, The Rockefeller University Medical of Kansas had one of the top schools of Laboratories Center. Successes in the development of new pharmacy in the United States and strong Clement Chow, PhD [email protected] drugs, devices, and procedures attract patients leadership in medicinal and pharmaceutical Postdoctoral Scientist Meredith Crosby, PhD Cornell University who want to benefi t from cutting-edge care, chemistry. It also had conducted research that Postdoctoral Scientist [email protected] and they attract funding from donors with an led to the commercialization of several drug Yale University/Procter & Gamble interest in supporting promising work that products. But none of those products had been Ida Chow, PhD [email protected] Executive Offi cer could lead to new treatments. tested in patients at the university’s medical Geraldine Dawson, PhD Society for Developmental Biology Scott Weir, PharmD, PhD, Director, center, which is located 42 miles away from the Chief Science Offi cer [email protected] Institute for Advancing Medical Innovation, School of Pharmacy. Additionally, its cancer Autism Speaks University of Kansas Cancer Center, described biology program was in its infancy and did not Stanley Cohen, MD [email protected] Chair the evolution of the extensive network have a rich, potential source of novel cancer Paul Dechow, PhD Department of Pathology Professor and Vice-Chair of partners that formed around efforts to drug targets. To achieve its goal of becoming UMDNJ-New Jersey Medical School establish a center of excellence for cancer at one of the top university-based cancer centers Department of Biomedical Sciences [email protected] Baylor College of Dentistry his institution. Establishing a National Cancer in bench-to-bedside translation, the university Texas A&M Health Science Center Institute-designated cancer center became a identifi ed the need to establish translational [email protected]
10 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 35
FASEB Report Layout.FINAL.indd Spread 16 of 28 - Pages(10, 35) 3/20/12 5:19 PM Anne M. Deschamps, PhD Mary C. Farach-Carson, PhD on the resources that are funded by Rockefeller’s Science Policy Analyst Associate Vice Provost for Research CTSA. Support for statistical work comes from Federation of American Societies for Experimental Rice University The Human as the Best Biology [email protected] its biostatisticians, and its facilitation offi ce [email protected] has helped shepherd protocols from initial Animal Model Fred Finkelman, MD Paul DiCorleto, PhD McDonald Professor of Medicine conceptualization to fi nal approval. She has had Chair, Lerner Research Institute Professor of Pediatrics to lean heavily on the clinical staffi ng in the “I come from a family of clinical Cleveland Clinic University of Cincinnati College of Medicine ffi [email protected] outpatient clinic, and the Institutional Review physicians, and there has been, [email protected] Board (IRB) has helped improve the quality Michael Fleming, MD, MPH always, a little bit of a mistrust from Loretta Doan, PhD Professor of her protocols. Working with Rockefeller’s Director, Science Policy Northwestern University hospital, she was able to obtain access to the my end [as] the basic scientist. I The Endocrine Society m-fl [email protected] [email protected] darkened space that she needed for her own always felt that clinical research was Susan Foy research by acquiring repurposed rooms that Chhanda Dutta, PhD either not rigorous enough or boring. Graduate Student had been used for sleep studies. Her work would Chief, Clinical Gerontology Branch Cleveland Clinic Lerner College of Medicine of Case And my parents and siblings always Division of Geriatrics and Clinical Gerontology Western Reserve University not have been possible without these resources. National Institute on Aging [email protected] A focus on translational research also felt that basic research was not really National Institutes of Health benefi ts trainees and early career scientists. [email protected] Martin Frank, PhD useful to them when they would see, Executive Director It provides important training opportunities American Physiological Society maybe, the outcome of it in their Steven Dworkin, PhD for graduate students and postdoctorates and Professor and Chair of Psychology [email protected] Western Illinois University may help to attract new talent into biomedical practice 10, 20, or 30 years later—if Maryrose Franko, PhD [email protected] Senior Program Offi cer research. Cindy Farach-Carson, PhD, Vice they’re lucky. Yet their patients need Michael Dyer, PhD Howard Hughes Medical Institute Provost for Translational BioScience, Rice [email protected] an answer now. I have had a clinical Member University, noted that translational research St. Jude Children’s Research Hospital Richard Galbraith, MD, PhD appeals to today’s generation of university fellow in my laboratory. This has [email protected] Professor of Medicine and Associate Dean students—many of whom want to work on University of Vermont provided a little dose of humility David J. Eckstein, PhD [email protected] “big, real world problems.” on both ends and fostered the idea Senior Health Scientist Administrator Farach-Carson also emphasized that Offi ce of Rare Diseases Research Bill Galey, PhD that we can, in fact, both make an National Institutes of Health Director of Graduate and Medical Education Programs establishing the infrastructure to conduct [email protected] Howard Hughes Medical Institute translational research provides opportunities impact quickly while learning from [email protected] for all of an institution’s investigators—not just Joel Ernst, MD clinical studies. From our clinical Professor Nao Gamo, MPhil those working on bench-to-bedside projects. NYU School of Medicine Graduate Student The collaboration necessary for conducting samples, we’ve learned a lot about [email protected] Yale University [email protected] this kind of work involves sharing expensive transcriptome editing that we Sindy Escobar Alvarez, PhD equipment, forming equipment cores, and Howard Garrison, PhD Program Offi cer for Medical Research probably wouldn’t have trusted had Director, Offi ce of Public Affairs developing policies for sharing, which can work Doris Duke Charitable Foundation Federation of American Societies for Experimental to everyone’s advantage. For example, Rice’s $9 it come from mouse studies alone. [email protected] Biology [email protected] million supercomputer from IBM came with Mary Estes, PhD F. Nina Papavasilou, PhD, the condition that it be shared in an affordable Associate Professor and Head of the Professor of Molecular Virology and Co-Director Eric Green, MD, PhD Graduate Program in Translational Biology and Director way with the Texas Medical Center and others Laboratory of Lymphocyte Biology, Molecular Medicine National Human Genome Research Institute outside the center. The Rockefeller University Baylor College of Medicine National Institutes of Health [email protected] [email protected]
36 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 9
FASEB Report Layout.FINAL.indd Spread 15 of 28 - Pages(36, 9) 3/20/12 5:19 PM study smell for many years before turning to results; exposure to new fi elds and methods Lawrence Green Jennifer A. Hobin, PhD people where, she said, “all the interesting action leading to new projects; and rapid publication Communications Specialist Director of Science Policy Federation of American Societies for Experimental Federation of American Societies for Experimental is.” Today, she studies how humans discriminate rate. Indeed, Wagner noted that three papers Biology Biology among smells, how genetic variation in humans were generated from the nanobubble project [email protected] [email protected] alters how they perceive odors, and how in the year preceding the meeting, equal to the Nadja Grobe, PhD Marybeth Howlett, MEM mosquitoes react to our smell. Her laboratory output of all of his other projects combined. Postdoctoral Research Fellow Managing Director is one of the biggest users of the Rockefeller Wright State University The Society of Nuclear Medicine outpatient clinic and has run upwards of 1,500 In sum, participation in translational [email protected] [email protected] volunteers through these olfaction studies. research benefi ts basic scientists by: Lauren Gross, JD Valerie Hu, PhD Director of Public Policy and Government Affairs Professor of Biochemistry and Molecular Biology Pursuing translational research also had • Enabling them to contribute to the benefi ts for Daniel Wagner, PhD, Assistant The American Association of Immunologists The George Washington University Medical Center understanding of human health and disease [email protected] [email protected] Professor, Department of Biochemistry and and to participate in the development of Lisa Guay-Woodford, MD Geoff Hunt, PhD Cell Biology at Rice University. A basic solutions to medical and public health developmental biologist working in zebrafi sh, Professor and Vice Chair Science Policy Fellow problems, which can be a source of University of Alabama at Birmingham American Society for Biochemistry & Molecular Biology Wagner embarked on a collaborative project intellectual inspiration and stimulation. [email protected] [email protected] with a physicist after encountering him • Providing opportunities to develop their Kathi Hanna, PhD Richard Insel, MD reading one of Wagner’s posters in the hallway. Science and Health Policy Consultant Chief Scientifi c Offi cer The physicist was working on a theranostic own science and learn new methods, which [email protected] Juvenile Diabetes Research Foundation (therapeutic–diagnostic) application for can lead to new projects, fresh directions for [email protected] existing projects, and faster publication rates. Rebecca Hartley, PhD plasmonic nanobubbles, in which gold particles Associate Professor Rebecca Jackson, MD are excited by short laser pulses to generate • Promoting collaborations with clinicians, University of New Mexico Health Sciences Center Associate Dean for Clinical Research transient vapor bubbles. The biologist and the clinical researchers, and basic investigators [email protected] The Ohio State University [email protected] physicist joined up to test the concept that in other disciplines, which can ignite shared Philip Haydon, PhD these nanobubbles could be used to identify passion, provide exposure to new areas of Annetta and Gustav Grisard Professor and Joseph Kemnitz, PhD cells based on their expression of specifi c cell Chair Department of Neuroscience Director, Translational Technologies and Resources science, and generate new ideas. Tufts University School of Medicine University of Wisconsin Madison surface molecules and to destroy specifi c cells in [email protected] [email protected] a zebrafi sh. The team used these nanobubbles • Providing opportunities to mentor clinical targeted to the EGF receptor and was able colleagues in basic science methods. Anthony Hayward, MD, PhD Khandan Keyomarsi, PhD Director, Division for Clinical Research Resources Professor to destroy prostate cancer cells within a host National Center for Research Resources University of Texas MD Anderson Cancer Center embryo. This was the fi rst step—proof of Benefi ts to Institutions National Institutes of Health [email protected] principle—that the theranostic method can be Institutions also benefi t from creating an [email protected] Robert Kimberly, MD used in vivo as a potential diagnostic tool and environment conductive to translational science. Joseph (JR) Haywood, PhD Senior Associate Dean for Research ultimately for targeted therapy. Their efforts help their scientists by facilitating Chair, Deparment of Pharmacology University of Alabama at Birmingham “As I saw the group that was being access to resources that they may not have had Michigan State University [email protected] [email protected] assembled around this plasmonic nanobubble before and connecting them to collaborators Stephen Korn, PhD project, I really began to think that there were with whom they share research interests, Terry Hébert, PhD Director of Training and Career Development some serious benefi ts for me, as a basic scientist, but otherwise may not have met. These Associate Professor National Institute of Neurological Disorders and Stroke McGill University National Institutes of Health and the potential to move this technology synergies move research forward, benefi tting [email protected] [email protected] forward and ultimately translate it into the the individual and his or her institution. For clinic,” said Wagner. Among the benefi ts he example, at The Rockefeller University, Vosshall Mary J.C. Hendrix, PhD Sally Kornbluth, PhD President & Scientifi c Director Vice Dean for Research cited were participation in a quickly moving noted that in order to carry out her studies on Children’s Memorial Research Center Duke University School of Medicine multi-investigator project that produced novel the sense of smell, she increasingly has to rely [email protected] [email protected]
8 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 37
FASEB Report Layout.FINAL.indd Spread 14 of 28 - Pages(8, 37) 3/20/12 5:19 PM Henry Krause, PhD Marc Malandro, PhD he learned a great deal about genetic diseases, Professor Associate Vice Chancellor for Technology Management the molecular causes underlying disease, and University of Toronto and Commercialization [email protected] University of Pittsburgh validation of drug targets, and he started to look [email protected] for translational research opportunities that Joel Kupersmith, MD were within reach of his academic laboratory. Chief Research & Development Offi cer Francesco Marincola, MD test chemotherapeutics. Not wanting to rely U.S. Department of Veterans Affairs Tenured Senior Investigator solely on a genetic model, they also developed His commitment to the fi eld increased when [email protected] Clinical Center Department of Transfusion Medicine a “xenographic” mouse model in which human a group of highly motivated Clinical Scholars National Institutes of Health joined his laboratory. These clinicians were Michael Kurilla, MD, PhD [email protected] tumor cells are transplanted to an eye of an Director immunocompromised mouse. This results in attracted to his work primarily because of its National Institute of Allergy and Infectious Diseases Priscilla Markwood, CAE virtually 100 percent engraftment with tumors specialized methods for characterizing small Director of Scientifi c Affairs, Communications National Institutes of Health expressing high levels of MDMX. Collaborations regulatory RNAs and their targets, but their [email protected] & Society Services American Society for Investigative Pathology with his chemical biology colleagues, who projects rapidly expanded and touched on Jennifer Kwan [email protected] were able to synthesize an MDMX inhibitor, and many aspects of gene regulation. He had not Policy Chair Bettie Sue Masters, PhD clinicians, who provided medical information anticipated the strong interest that the clinical American Physician Scientists Association investigators would have in basic science and M.D.-Ph.D. Candidate The Robert A. Welch Distinguished Chair in Chemistry and tumor specimens, enabled Dyer to begin a University of Texas Health Science Center San Antonio Medical Scientist Training Program preclinical trial focused on inhibiting MDMX. new methodologies, and he found that pairing [email protected] University of Illinois at Chicago each clinician with a basic investigator resulted Dyer believes that the process by which basic [email protected] Donald McClain, MD, PhD in a considerable amount of synergy between Program Director investigators can translate their discoveries into Megan Lassig the two. University of Utah clinical applications could be emulated at most Program Assistant Without the expertise that the clinicians [email protected] major medical or academic research centers. The Howard Hughes Medical Institute brought to his laboratory, Tuschl says he might [email protected] building blocks important for driving translation, Dennis McKearin, PhD have never understood how to operate and Senior Scientifi c Offi cer such as strong basic science departments, animal Anh-Chi Le, PhD devise experiments relevant to translational Howard Hughes Medical Institute research facilities, pharmacology and pathology Program Offi cer [email protected] medicine. By working with human tissue Howard Hughes Medical Institute departments, and clinical trial support are already samples, observing the variation among [email protected] Matthew McMahon, PhD in place. He also noted that some translational individuals and in sample collection, following Senior Advisor for Translational Research work can be done with relatively few resources, Stephanie Lederman, EdM National Eye Institute the clinicians’ progress at the bench, and Executive Director if one acts creatively. He received no support from National Institutes of Health accessing their data, he learned how to adapt American Federation for Aging Research [email protected] St. Jude to fund these studies directly. Rather, [email protected] Dyer built on a one-year pilot grant of $50,000 and his methods to study hundreds of patient and Sally McNagny, MD, MPH control samples. In return, the scholars have Grace Lee, PhD cobbled the rest together through other sources. Vice President found it helpful to train with a basic scientist, Pharmacology/Toxicology Reviewer The Medical Foundation, a division of HRiA U.S. Food and Drug Administration [email protected] The challenge, he said, is changing the culture. which offered them a completely new strategy [email protected] Emphasizing the value of translational research for understanding biological phenomena. Elizabeth McNally, MD, PhD to both basic and clinical scientists, encouraging Yung Lie, PhD Professor of Medicine and Human Genetics For basic biologists, engaging in Scientifi c Director Director, Institute for Cardiovascular Research communication between basic and clinical translational research has benefi ts that go Damon Runyon Cancer Research Foundation Director, Cardiovascular Genetics Clinic scientists, mentoring, and understanding the beyond contributing to understanding and [email protected] President Elect clinical reality of disease progression and treating human disease. It helped Leslie Vosshall, American Society for Clinical Investigation therapeutic interventions are all important for Yvonne Maddox, PhD [email protected] PhD, Robin Chemers Neustein Professor and Deputy Director increasing participation in translational research Head of the Laboratory of Neurogenetics and Francis Miller, MD National Institute of Child Health and and ultimately improving human health. Behavior at The Rockefeller University, to Human Development Associate Professor of Medicine National Institutes of Health University of Iowa learn more about her fi eld. Trained as a basic [email protected] [email protected] biomedical researcher, Vosshall used insects to
38 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 7
FASEB Report Layout.FINAL.indd Spread 13 of 28 - Pages(38, 7) 3/20/12 5:19 PM Thomas Miller, PhD Margaret Offermann, MD, PhD Box B: Making a Diff erence Program Director Principal Taking the Challenges of the Clinic Back to the Laboratory National Institute of Neurological Disorders and Stroke The Salutramed Group National Institutes of Health [email protected] [email protected] Frederick Ognibene, MD When Michael Dyer, PhD, fi rst arrived at St. Jude as a junior faculty member nine years ago, Daria Mochly-Rosen, PhD Deputy Director Educational Affairs & Strategic he was the head of a basic developmental neurobiology research laboratory. One day, while Senior Associate Dean for Research Partnerships deciding how to set up his laboratory space, there was a knock at his door. Two clinicians Professor Chemical & Systems Biology National Institutes of Health Stanford University [email protected] who treat retinoblastoma patients asked him to spend some time with them in the clinic. He [email protected] realized that after spending fi ve years at a major medical center and studying normal eye Alex Ommaya, DSc development and genetic mutations of the eye, he had never once met a clinician, patient, or Katie Moore, PhD Director Translational Research Manager, Science Policy patient’s family. He eagerly accepted the opportunity. U.S. Department of Veterans Affairs The Endocrine Society [email protected] [email protected] Dyer knew that Rb gene mutations cause retinoblastoma, a rare childhood cancer with only Rebecca Osthus, PhD Mariana Morris, PhD 300 cases per year in the United States. But when he asked the clinicians if the tens of Science Policy Analyst Professor and Chair thousands of papers available on PubMed on the Rb gene and pathway had any impact on American Physiological Society Assistant Vice President for Graduate Studies [email protected] how patients are treated, they replied that they had no impact whatsoever. This surprising Wright State University response led him to change the direction of his career and the research direction of his [email protected] F. Nina Papavasiliou, PhD, laboratory. Cynthia Morton, MD Associate Professor and Head of the Laboratory Professor of Obstetrics/Gynecology and Pathology of Lymphocyte Biology To Dyer, the reason these basic research papers had not been translated into new therapies Brigham and Women’s Hospital The Rockefeller University was obvious: there was a lack of good animal models for this disease. Researchers had Harvard Medical School [email protected] tried to develop a retinoblastoma model by deleting the Rb gene from the mouse genome, [email protected] Todd Peterson, PhD but the manipulation did not cause the mouse to develop retinoblastoma. Unbeknownst to Karen Mowrer, PhD Assistant Professor them at the time, another protein, p107, is able to compensate for Rb in the mouse. When Legislative Affairs Offi cer Vanderbilt University both Rb and p107 are deleted from the mouse genome, retinoblastoma develops in about Federation of American Societies for Experimental [email protected] 50 percent of the animals. Using this model, he was able to test different therapeutics against Biology [email protected] Sharma Prabhakar, MD, MBA, FACP the disease. In doing so, Dyer applied what he learned from his clinical colleagues about Professor and Chief of Nephrology the actual course of treatment in patients (i.e., clinical reality) and tested combinations of James Musser, MD, PhD Vice-Chair, Dept of Medicine broad-spectrum systemic chemotherapeutics in a similar manner in his mice. After going Chair Texas Tech University Health Sciences Center Department of Pathology and Laboratory Medicine [email protected] through eight different combinations of drugs and comparing them to the current standard The Methodist Hospital of care, Dyer and his colleagues found a combination that seemed to be better than what [email protected] M. Renee Prater, PhD, DVM children currently were receiving. St. Jude started a new fi ve-year clinical trial based on those Associate Professor and Chair of Immunology Elizabeth Myers, PhD data. Although going from nothing to a new clinical trial in about 18 months was satisfying, Edward Via College of Osteopathic Medicine Program Director [email protected] Dyer hoped to do better. He wanted to develop a more targeted chemotherapy that could be Doris Duke Charitable Foundation delivered locally to the eye and result in fewer side effects. [email protected] Alice Ra’anan Director of Science Policy Searching for a drug target, Dyer’s team discovered that patients with retinoblastoma Lee Nadler, MD American Physiological Society Dean of Clinical and Translational Research [email protected] have increased levels of MDMX, which sequesters p53, a tumor suppressor, and leads to Harvard Medical School cell proliferation and tumor development. MDMX is amplifi ed in 65 percent of patients and [email protected] J. Usha Raj, MD epigenetically turned on in the rest. Professor and Head Kim Ngo University of Illinois at Chicago Public Affairs Assistant Now having a target to go after, Dyer and colleagues developed a model in which the [email protected] Federation of American Societies for Experimental MDMX gene was conditionally over expressed in the mice that develop retinoblastoma. This Biology resulted in a much more aggressive disease in these animals—providing a new model to [email protected]
6 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 39
FASEB Report Layout.FINAL.indd Spread 12 of 28 - Pages(6, 39) 3/20/12 5:19 PM Marc Reitman, MD, PhD Douglas Sheeley, ScD Branch Chief Senior Scientifi c Offi cer The Benefi ts of Engaging in National Institute of Diabetes and Digestive National Center for Research Resources and Kidney Diseases National Institutes of Health Translational Research National Institutes of Health [email protected] [email protected] Susan Shurin, MD Makeda Richardson Acting Director The ultimate goal of translational biomedical research is to improve human Program Assistant National Heart, Lung, and Blood Institute health—an outcome that benefi ts all of society. But participating in Graduate Science Education National Institutes of Health translational science also has more direct and immediate rewards for Howard Hughes Medical Institute [email protected] individual investigators and the institutions that support their work. [email protected] Hadley Sikes, PhD Three teams of panelists—paired as basic scientists and senior leaders Rose Marie Robertson, MD Assistant Professor from the same university—discussed these benefi ts from their Chief Science Offi cer Massachusetts Institute of Technology respective vantage points. American Heart Association [email protected] [email protected] David Skorton, MD Benefi ts to Scientists Michael Rosenblatt, MD President The opportunity to conduct research that has an impact on human health is Executive Vice President Cornell University a signifi cant factor in many scientists’ decisions to participate in translational Chief Medical Offi cer [email protected] research. Nearly three-quarters of the respondents to FASEB’s survey indicated Merck & Co. Paul Dechow, PhD, Jacqueline Slavik, PhD that they initially embarked on translational work because they wanted to have [email protected] Professor and Vice Executive Director an impact on a particular disease or condition, and more than half wanted to Theodora Ross, MD, PhD Biomedical Research Institute Chair, Department of Professor Brigham and Women’s Hospital Biomedical Sciences, have an impact on human health in general. (See survey insert, page 22.) This University of Michigan [email protected] Baylor College of sentiment was echoed by Dirk Schnappinger, PhD, Associate Professor, Weill [email protected] Dentistry, Texas A&M Cornell Medical College, who is working to validate new targets for the discovery Bonnie Sloane, PhD Health Science Center of drugs to treat tuberculosis. He noted that he and his team, which includes Doris Rubio, PhD Distinguished Professor & Chair Professor of Medicine Wayne State University collaborators from 13 institutions around the world, “are motivated by having an University of Pittsburgh [email protected] impact on global health and can attract people who share that desire.” Likewise, [email protected] for Michael Dyer, PhD, an HHMI Early Career Scientist and a basic biologist John Smith, MD, PhD, MMM, DSC (Hon) Alisa Schaefer, PhD Director, Division of Laboratory Medicine studying retinal development at St. Jude Children’s Research Hospital, the Advisor for Global Outreach Professor of Pathology realization that the tens of thousands of papers on the genetics of retinoblastoma National Institutes of Health University of Alabama at Birmingham had not yet affected the way patients with the disease are treated “fundamentally [email protected] [email protected] changed the direction of [his] career and the research direction of [his] lab.” Dirk Schnappinger, PhD Mark Sobel, MD, PhD (See Box B.) Associate Professor of Microbiology and Immunology Executive Offi cer Thomas Tuschl, PhD, Associate Professor and Head of the Laboratory for Weill Cornell Medical College American Society for Investigative Pathology RNA Molecular Biology at The Rockefeller University, also wanted to apply [email protected] [email protected] his science to the study of disease; partnering with clinicians helped him to do Jacob Schumacher Anita Miller Sostek, PhD that. Trained as a basic scientist, he obtained his doctoral degree in chemistry, Legislative Aide Vice President for Scientifi c Review and Operations conducted postdoctoral work in biochemistry, and then became interested in The American Association of Immunologists Autism Speaks the therapeutic applications for gene silencing through the discovery of sRNAs [email protected] [email protected] and microRNAs as regulators of gene expression. His current work is focused on Harry Shamoon, MD Tyrone Spady, PhD defi ning the molecular pathology leading to specifi c diseases and developing Associate Dean Science Policy Analyst targeted approaches suitable for therapeutic interventions. Clinical and Translational Research Federation of American Societies for Experimental Tuschl had developed an appreciation for translational science and its Albert Einstein College of Medicine Biology [email protected] [email protected] challenges while working with the pharmaceutical industry. As a cofounder and scientifi c advisor to Alnylam Pharmaceuticals and Regulus Therapeutics,
40 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles 5
FASEB Report Layout.FINAL.indd Spread 11 of 28 - Pages(40, 5) 3/20/12 5:19 PM pharmaceutical research organizations, and track record of supporting fundamental science Patrick Stover, PhD Matt Walter, MD scientifi c societies; and scientifi c publishers. and an interest in advancing human health Professor and Director Assistant Professor of Medicine Division of Nutritional Sciences Washington University School of Medicine (For the agenda and a full list of registrants, and the treatment of disease. To supplement Cornell University [email protected] see Appendix 1 and Appendix 2.) Meeting information provided in the presentations, [email protected] participants explored the benefi ts of engaging FASEB conducted a survey of meeting Ena Wang, MD Nancy Sung, PhD Staff Scientist basic scientists in translational research, the participants and nearly 2,000 FASEB society Senior Program Offi cer Clinical Center Department of Transfusion Medicine obstacles that stand in their way, and the role scientists. This report describes the major survey Burroughs Wellcome Fund National Institutes of Health that research institutions, funders, professional results (see survey insert, page 22), summarizes [email protected] [email protected] societies, and scientifi c publishers can play to the proceedings of the meeting, and offers a Bernard Talbot, MD, PhD Scott Weir, PharmD, PhD help basic scientists overcome these obstacles. practical set of recommendations for engaging Medical Offi cer Director The meeting was hosted by the Howard basic scientists in translational research. FASEB’s National Center for Research Resources Institute for Advancing Medical Innovation Hughes Medical Institute (HHMI) in Chevy goal is to foster the creation of an environment National Institutes of Health University of Kansas [email protected] [email protected] Chase, Maryland, and was co-sponsored by that encourages basic scientists to consider the the Burroughs Wellcome Fund, the U.S. translational potential of their work and to William Talman, MD Jennifer Westendorf, PhD Department of Veterans Affairs, the Doris Duke pursue opportunities to apply their knowledge Professor of Neurology and Neuroscience Associate Professor University of Iowa Mayo Clinic Charitable Foundation, and Merck Sharp & and expertise to investigations directly relevant [email protected] [email protected] Dohme Corp. All fi ve organizations have a long to improving human health and treating disease. Thomas Tuschl, PhD Andrea Widener, MA Associate Professor and Head of the Laboratory Science Writer for RNA Molecular Biology Howard Hughes Medical Institute The Rockefeller University [email protected]
Mark Tykocinski, MD Heng Xie, MD, MPH, PhD Dean Supervisory Medical Offi cer Jefferson Medical College National Center for Research Resources [email protected] National Institutes of Health [email protected] Rod Ulane, PhD NIH Research Training Offi cer Wen Xie, MD, PhD National Institutes of Health Associate Professor [email protected] University of Pittsburgh [email protected] Leslie Vosshall, PhD Robin Chemers Neustein Professor Liming Yang, PhD Head of the Laboratory of Neurogenetics and Behavior Program Offi cer The Rockefeller University National Center for Research Resources National Institutes of Health Daniel Wagenaar, PhD [email protected] Broad Senior Research Fellow in Brain Circuitry California Institute of Technology Jennifer Zeitzer [email protected] Director of Legislative Relations Federation of American Societies for Daniel Wagner, PhD Experimental Biology Assistant Professor, Department of Biochemistry [email protected] and Cell Biology Rice University [email protected]
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FASEB Report Layout.FINAL.indd Spread 10 of 28 - Pages(4, 41) 3/20/12 5:19 PM Appendix 3: Resources to Facilitate Participation in Translational Research The NIH Clinical Center is the nation’s largest hospital devoted entirely to clinical research. It conducts and supports research into the pathogenesis of disease; fi rst-in-human clinical trials; the development of This appendix supplements the report recommendations by providing examples of policies, programs, state-of-the-art diagnostic, preventive, and therapeutic interventions; and clinical research training. and practices that could facilitate the engagement of basic scientists in translational research. It is not intended to be a comprehensive list. Rather, it aims to give a general “fl avor” of the types of The Clinical and Translational Science Award (CTSA) program creates a defi nable home for clinical and translational approaches institutions, including universities, funding organizations, and professional societies, may research at academic health centers across the nation. CTSA consortium institutions are building capabilities in want to adopt. connecting basic scientists with clinically experienced researchers to support training and to build a fully functional national network.
Resource, Policy, Organization The NIH-Food and Drug Administration Partnership spearheads collaborative work on important public health or Program (weblink) Description Purpose issues. The Joint Leadership Council works together to help ensure that regulatory considerations form an integral component of biomedical research planning and that the latest science is integrated into the regulatory review process. ESTABLISHING COLLABORATIONS The Cures Acceleration Network was established to advance the development of high-need cures and reduce BiomedExperts BiomedExperts Enables social networking to help scientists Identify collaborators http://www.biomedexperts.com share data and search for potential and expertise; share barriers to translation by providing new funding mechanisms and fl exibility to help NIH more effectively manage collaborators based on their areas of data projects. expertise and professional networks. The National Center for Advancing Translational Sciences brings together many of the above listed components, Collaboration and National Institutes of Health Provides assistance to investigators who are Provide information Team Science: http://tinyurl.com/75r8foz participating on, leading, or contemplating on collaboration and among others, into one cohesive entity. It will support partnerships to provide resources for investigators at all stages A Field Guide building a research team. Topics include team science along the pipeline and enhance training and disciplines related to translational sciences, such as clinical pharmacology. building a research team, developing a The new Center is not intended to duplicate current activities in the other NIH Institutes and Centers, but rather to shared vision, sharing recognition and credit, facilitate them and catalyze collaborations across the NIH enterprise. and handling confl ict. Collaborative National Institutes of Health Provides a template for developing a Facilitate Agreement http://tinyurl.com/cdohgwm collaborative agreement that explicitly collaborative Template states the team’s expectations, goals, and agreements values. This template is contained in NIH’s “Collaboration and Team Science: A Field Guide” (see above). Global Centers Pfi zer, University of California Network of partnerships with academic Foster collaboration for Therapeutic San Francisco medical centers (AMCs) designed to develop to promote drug Innovation http://tinyurl.com/4mlmdhp biologic therapeutic candidates. Centers are development jointly staffed by Pfi zer employees and basic the current research environment—one challenges can limit professional interest in the and translational scientists and doctoral that encourages specialization and rewards fi eld and hamper the translational enterprise. candidates from AMCs. Pfi zer provides investigators with access to its resources individual achievement and hypothesis-driven To address these issues, the Federation of and incentivizes participation through research. In addition, basic investigators American Societies for Experimental Biology milestone payments, publishing rights, and may face inadequate funding, resources, or (FASEB) held a symposium March 24-25, intellectual property use. infrastructure for developing translational 2011, that brought together basic and clinical research programs. Furthermore, they often lack research trainees and scientists, department suffi cient experience with essential methods and heads, and senior leaders from diverse academic techniques, as well as with complex regulatory research institutions; the leadership of private requirements, to be effective in this realm. These and public research funding organizations,
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FASEB Report Layout.FINAL.indd Spread 9 of 28 - Pages(42, 3) 3/20/12 5:19 PM Box A: Translational Research at NIH Resource, Policy, Organization or Program (weblink) Description Purpose
ESTABLISHING COLLABORATIONS (continued) NIH Director Francis Collins, MD, PhD, opened the symposium with a presentation titled “Catalyzing Opportunities in Translational Research.” He emphasized NIH’s Harvard Harvard University Provides a research networking and Identify expertise, Catalyst Profi les http://tinyurl.com/7lkqyaj expertise mining software tool that connects collaborators continued support for basic science and the important contributions it makes to the people by combining basic directory translational research pipeline. Dr. Collins also provided an overview of NIH efforts to information with expertise keywords. Each promote and facilitate the movement of basic science discoveries into therapeutic person in the network has a profi le page that applications. Those efforts are described below. includes his or her name, titles, affi liations, and contact information. Enables the creation of automatically formed passive networks NIH-Supported Basic Research accounts for approximately 52 percent of its based on shared traits (e.g., publications, research portfolio. A good deal of this work is aimed at understanding the molecular departments) and active networks defi ned by basis of disease and identifying potential therapeutic targets. the user. Research Multiple, including Describes speed networking sessions that Identify expertise, The NIH Molecular Libraries program offers public-sector biomedical researchers access to the large-scale screening “Speed Dating” Cornell and Dalhousie aim to spark collaborations across disciplines collaborators capacity necessary to identify small molecules that can be optimized as chemical probes to study the functions of Universities and institutions. Participants (e.g., academic genes, cells, and biochemical pathways. The goal of this program is to lead to new ways to explore the functions of http://tinyurl.com/7h3b82o; investigators, industry scientists, physicians) are given two to three minutes to exchange genes and signaling pathways in health and disease. http://tinyurl.com/7fouycf cards, biographies, and research interests before moving on to share the same The Therapeutics for Rare and Neglected Diseases program encourages and speeds the development of new information with the next participant. drugs for rare and neglected diseases. This unique program creates a drug development pipeline within NIH and Research Team Northwestern University Offers collaboration enhancement for Provides support for is specifi cally intended to stimulate research collaborations with academic scientists, nonprofi t organizations, and Support and Clinical and Translational team-based, cross-disciplinary translational team science pharmaceutical and biotechnology companies working on rare and neglected illnesses. Development Sciences Institute biomedical research and helps translate http://tinyurl.com/6rxxsqh research fi ndings about team science into The Bridging Interventional Development Gaps program (formerly the Rapid Access to Interventional Development effective practices for teams and funders. [RAID] program) makes available, on a competitive basis, certain critical resources needed for the development of Resources include expert/collaborator identifi cation and referral, collaboration new therapeutic agents. Available services include the production, bulk supply, GMP manufacturing, formulation, and facilitation, team science tools and development of an assay suitable for pharmacokinetic testing and animal toxicology. Assistance also is provided with resources, collaborative research funding the regulatory process. information, collaborative research program development, and team science training. SciVal Experts SciVal Experts Provides a directory of research expertise Identify expertise, http://preview.tinyurl. prepopulated with publication histories from collaborators com/7pn9pd2 Elsevier’s Scopus database. It provides a visual analysis of relevant concepts that compounds in molecular, cellular, and animal opportunities, funding agencies such as NIH instantly exposes a researcher’s distinctive expertise. It also can incorporate institutional models. Recent research breakthroughs provide have instituted an array of translational research data and individual researcher updates. an ever-widening landscape of opportunities for programs (see Box A). VIVO Multiple; available to institutions Provides an open source semantic web Identify research, basic investigators to work in these areas. These However, a number of obstacles—scientifi c, with relevant technology application that enables the discovery of scholarship, and include the completion of the Human Genome institutional, cultural, and policy—have limited http://www.vivoweb.org/ research and scholarship across disciplines collaborators Project and dramatic advances in information the opportunities for basic investigators to and institutions by creating a semantic technology; biocomputing; high-throughput conduct translational science. This work cloud of information that can be searched and browsed. It is populated with detailed technologies for screening, identifying, and is best conducted through multi- and profi les of faculty and researchers including studying compounds of interest; and novel interdisciplinary collaborations, which can information on publications, teaching, imaging capabilities. Recognizing these be diffi cult to establish and maintain in service, and professional affi liations.
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IDENTIFYING RESEARCH TOOLS AND RESOURCES Basic scientists are the foundation of the biomedical research enterprise. CTSA Multiple Facilitates matches between CTSA-affi liated Identify research Their work is key to understanding fundamental biological processes and Pharmaceutical http://www.ctsapharmaportal. investigators and the pharmaceutical compounds, Assets Portal org/aboutus.html industry to develop research partnerships expertise, and mechanisms of disease pathogenesis, and it has been critical to preventing, based on potentially valuable compounds collaborators diagnosing, and treating diseases and conditions that affl ict millions of that did not make it to the market. Academic people. Yet despite major advances in fundamental biology, there is researchers can submit proposals to pharma partners requesting a specifi c drugs or a widespread concern about the slow pace at which these discoveries are drug category with a desired effect. Pharma translated into safe and effective clinical interventions. The National partners can contact target experts identifi ed Institutes of Health (NIH) estimates that 80 percent to 90 percent of from clusters of researchers organized potential therapeutics in preclinical testing run into problems that preclude around areas of expertise. them from advancing to the clinical trial phase.1 Numerous initiatives to eagle-i Multiple; consortium of nine Prototype of a national research resource Identify research member institutions discovery network to help biomedical resources speed translation are under way at the national and institutional levels, many of https://www.eagle-i.net/ scientists search for and fi nd previously John A. Smith, MD, which have been aimed at providing clinical scientists with the knowledge and unknown, but highly valuable, resources. PhD, MMM, DSc tools needed to translate research discoveries into improved patient care. Less Resources accessible through the site (Hon), University attention, however, has been given to the contributions that basic scientists make include animal models, reagents, cell and tissue banks, core facilities, and training of Alabama at to the process of translational research. opportunities. Birmingham A somewhat fl uid and amorphous concept, translational research is the term used to describe a spectrum of scientifi c investigation aimed at: 1) transferring TRANSLATIONAL RESEARCH TRAINING laboratory discoveries about disease mechanisms into new methods for diagnosing, COALESCE Northwestern University Aims to create, evaluate, and disseminate Educate and preventing, and treating disease and testing these methods in humans; 2) taking online learning resources to enhance Clinical and Translational train researchers results from clinical studies into clinical practice and understanding the effi cacy Science Center skills needed to perform transdisciplinary, and institutional http://teamscience.net team-based translational research. Learning development offi cers and dissemination of health care interventions; and 3) using the knowledge modules help users acquire and apply in team research gained to improve health care policy. Scientists from many disciplines often knowledge of team science and provide an are involved in this work, ranging from the most basic investigators in the life, experiential learning environment where they can engage virtually in the challenges of chemical, physical, mathematical, engineering, and computer sciences to those team research. in the clinic. Research across the continuum does not always proceed linearly. Clinical and Northwestern University Provides a two-day program to educate Educate Often it is an iterative, bidirectional process in which insights into biological Translational http://tinyurl.com/bpwxaag medical students and undergraduates in undergraduate and mechanisms and disease processes inform and spur new clinical interventions Research Summer the skills required for biomedical research. medical students and, conversely, observations about the nature and progression of disease made in Seminar Series It covers topics including, biostatistics, epidemiology, responsible conduct of the course of patient care and clinical research stimulate new basic investigations. research, human subjects research, the This paper focuses on the former pathway. research enterprise, clinical trial conduct, Although individuals trained in basic science can contribute to research drug and device development, and career opportunities. at any point along this spectrum, their expertise is especially valuable during the fi rst, or “T1,” stage. This is where an understanding of human biology, Core Competencies CTSA Consortium A set of competencies within 14 thematic Educate graduate for Clinical and http://tinyurl.com/cyoxukh areas that defi ne the skills, attributes, and students, pathogenesis, and basic science methods converge to bear on the identifi cation Translational knowledge needed to conduct clinical and postdoctoral and characterization of disease targets, assay development, lead identifi cation and Research translational research. The competencies researchers, and high-throughput screening, and preclinical evaluation of potentially therapeutic can serve as a guide for anyone considering independent developing a translational curriculum at investigators 1 multiple graduate levels. National Institutes of Health. 2009. “NIH Announces New Program to Develop Therapeutics for Rare and Neglected Diseases.” Accessed May 30, 2011, at www.nih.gov/news/health/may2009/nhgri-20.htm.
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FASEB Report Layout.FINAL.indd Spread 7 of 28 - Pages(44, 1) 3/20/12 5:19 PM 3. Use their convening power to facilitate It is recommended that individual scientists Resource, Policy, Organization interaction and collaboration among basic who are open to the translational implications or Program (weblink) Description Purpose and clinical scientists in academe and of their work: industry. 1. Learn to defi ne a health need with the same TRANSLATIONAL RESEARCH TRAINING (continued) 4. Fund high school, college, graduate, and precision as a basic science hypothesis. Demystifying National Institutes of Health A weekly, one-hour course for PhDs that Educate graduate postdoctoral translational educational Medicine http://demystifyingmedicine. includes presentation of patients, pathology, students, 2. Seek mentors and collaborators from od.nih.gov/ diagnosis, and therapy in the context postdoctoral research programs and mentorship by basic, different disciplines. of major disease problems and current researchers, and translational, and clinical scientists. 3. Seek funding to work in the translational research. The course is designed to help independent bridge the gap between advances in biology investigators 5. Work together to evaluate the outcomes of space. and their application to major human efforts to promote translational research. 4. Be aware of promotion and tenure diseases. Each session includes clinical and basic science components presented by staff It is recommended that professional expectations and take responsibility for and outside invitees. societies: defi ning the intellectual areas for which Lucille P. Markey Washington University in St. Two-year course of study for graduate Educate and train 1. Spark interest in translational research by they will be recognized as leaders. Special Emphasis Louis students and postdoctorates that PhD students raising its profi le in featured symposia, It should be emphasized that it is not the Pathway in Human http://dbbs.wustl.edu/ supplements biomedical PhD education. It and postdoctoral workshops, and sessions at professional Pathobiology markeypathway includes a course in Pathobiology of Human researchers goal of FASEB or this initiative to convert basic Program Disease States, individualized clinical meetings. scientists into clinical researchers. Rather, the mentorship, and an annual retreat enabling 2. Provide resources and opportunities to goal is to foster the creation of an environment personal and scientifi c interactions between trainees and faculty. facilitate interactions among basic and that encourages basic biomedical researchers to clinical researchers. consider the translational potential of their work Masters of Science Stanford University Provides PhD students with exposure to Provide masters in Medicine Degree http://msm.stanford.edu/ medicine to foster translational research. level medical 3. Recognize the contributions basic scientists and ensure that there are opportunities to apply Program Students are required to complete PhD concept training for make in translation by providing awards or modern biological knowledge and expertise to course requirements and lab rotations. PhD students improving human health and treating disease. During the fi rst two years of the master’s other forms of recognition for translational, program, they participate in basic biomedical team, or interdisciplinary science. science courses alongside the university’s 4. Advocate for policy and programmatic medical students and take a seminar dedicated to issues in translational medicine. changes that would facilitate the In the second year, they choose thesis labs participation of basic investigators in and clinical mentors. translational research. MD-PhD Resources Association of American Medical Provides links to resources related to MD/ Provide information It is recommended that publishers: Colleges PhD training, including MD-PhD training about MD-PhD http://tinyurl.com/6wwa9eh programs in the United States and Canada training 1. Ensure that the role of individual authors is and workshops and research programs for clearly articulated in publications. students interested in pursuing combined MD-PhD training. 2. Encourage editors to identify and highlight Med into Grad Howard Hughes Medical Supports and encourages graduate schools Integrate medical the contributions that basic research Initiative Institute to integrate medical knowledge into their knowledge into PhD fi ndings could make to medicine and/or http://tinyurl.com/7n7szu3 PhD training. The program’s goal is to training public health. produce researchers who will recognize which biological problems are of the greatest 3. Prioritize the publication of papers that clinical relevance, have the knowledge and combine the study of clinical outcomes with skills necessary to facilitate the translation mechanistic considerations. of new biological knowledge into tools to improve human health, and be able to create fruitful research partnerships with physicians.
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FASEB Report Layout.FINAL.indd Spread 6 of 28 - Pages(vi, 45) 3/20/12 5:19 PM research funding programs and policies. Those Resource, Policy, Organization Challenges to Engaging Basic or Program (weblink) Description Purpose Scientists in Translational Research proposals were shaped by the symposium steering committee into a set of practical TRANSLATIONAL RESEARCH TRAINING (continued) Despite its benefi ts, initiating and sustaining recommendations aimed at the major a translational research program can be stakeholders and are summarized below. National CTSA University of Rochester Makes available a variety of clinical and Educate and train challenging. Speakers noted that basic Educational http://tinyurl.com/cqkgyhc translational educational modules from students and scientists tend to lack training in human It is recommended that research institutions Resource Program the CTSA consortium training programs investigators at all encourage and engineer a cultural shift and the NIH Institutes and Centers. The levels disease processes and translational research toward greater collaboration, cooperation, modules are specialized educational courses approaches. Furthermore, the physical and intended for audiences from K-12 students communication, and respect among basic and cultural separation of basic and clinical to experienced faculty and include a mix of clinical scientists by: departments at research universities often limits materials for web- and classroom-based 1. Providing didactic and experiential learning learning. opportunities for basic scientists to interact opportunities that place basic research with patients and to network with and learn Physiology The American Physiological Highlights translational research Educate graduate in the context of pathophysiology and InFocus: Society programming at the society’s annual meeting students, from clinicians and clinical researchers who pathobiology and by providing opportunities Physiology in http://tinyurl.com/7xopj9x; through designated sessions and meeting postdoctoral have skills that complement their own. Basic Medicine/ http://tinyurl.com/6wx2opr tracks. researchers, and to acquire training in the wide range of skills Translational independent scientists also may fi nd it diffi cult to obtain needed to conduct translational research. funding for translational work and to navigate Physiology Track investigators 2. Using multiple approaches to increase The Seminars University of Texas at Seminar series that brings together Promote education the maze of administrative and regulatory issues the interdisciplinary interactions among in Translational San Antonio investigators from basic, clinical, and social and collaboration involved. Those who do succeed may fi nd it academic and industry scientists and Research (STRECH) http://translationalseminars. sciences from multiple university campuses. diffi cult to publish their work in journals that trainees. utsa.edu/ Seminars highlight the translation of tend to favor hypothesis-driven research over research discoveries from bench to bedside 3. Revising tenure and promotion policies to community and promote the formation of goal-directed or applied science. Likewise, basic to recognize—not punish—creative and multidisciplinary clinical and translational science departments and tenure and promotion nontraditional risk-taking to advance research teams. committees may not attribute the same value translational science. Translational American Association for Provided an intensive week-long introduction Educate graduate to translational research as they would to basic 4. Connecting basic investigators to the Cancer Research Cancer Research to translational cancer research for basic students, research in the tenure and promotions processes. for Basic Scientists http://tinyurl.com/4xhtcsy scientists transitioning to translational postdoctoral infrastructure, equipment, and technical research. The goals were to provide researchers, and and administrative support necessary to participants a better understanding of independent Facilitating the Participation of Basic move their discoveries from the bench to translational research, teach them how to investigators Scientists in Translational Research the bedside. adapt their research for maximum clinical Translational research opportunities can be impact, and help them transition into a new It is recommended that funding agencies career in translational cancer medicine. facilitated through coordinated action by continue to support basic research to ensure Translational American Federation for Annual researcher-initiated and peer- Educate graduate research institutions, funders, professional a deep and broad reservoir of new knowledge Medical Research Medical Research reviewed seminar series showcasing bench- students, societies, scientifi c publishers, and basic upon which translational and clinical science Symposia Series http://www.afmr.org/eb2011.cgi to-bedside research addressing cutting postdoctoral investigators themselves. Conference participants can grow, and: and Workshop edge, clinically important topics. AFMR also researchers, and were asked to propose recommendations in four conducts a workshop to provide investigators independent 1. Provide specifi c funding for investigator- with perspectives and practical tools for investigators key areas: 1) helping basic scientists to acquire initiated translational research grants developing successful clinical-translational translational research training; 2) providing in addition to support for translational medical research programs. Workshops appropriate recognition and rewards for infrastructure and resources. topics have included drug development, the contributions basic scientists make to intellectual property, connecting research 2. Ensure that grant application review panels cultures, and managing confl ict of interest. translational research; 3) forging collaborations have the appropriate expertise to review among basic and clinical scientists in academe translational research projects rigorously and industry; and 4) optimizing translational and fairly.
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TRANSLATIONAL RESEARCH TRAINING (continued) Basic scientists play a key role in generating the research discoveries that TRIUMPH University of Texas (UT) Provides training in clinical and translational Educate and are translated into applications that improve human health. A number (Translational Graduate School of Biomedical research to postdoctoral researchers through train postdoctoral of obstacles—scientifi c, institutional, cultural, and policy—limit Research in Sciences, MD Anderson Cancer didactic course work, clinical rotations, researchers opportunities for basic scientists to conduct translational science and Multi-Disciplinary Center, UT Medical School and mentorship. The long-term goal is to produce translational scientists who can be may slow the pace at which discoveries are translated into clinical Program) http://tinyurl.com/3fprqhk Postdoctoral teamed with suitable physician scientists in applications. Researchers trained in basic science may face inadequate Fellowship translational research laboratories. funding, resources, or infrastructure for developing translational research programs; insuffi cient experience with essential methods and techniques; RECOGNIZING AND REWARDING TRANSLATIONAL RESEARCH complex regulatory requirements; or suboptimal recognition or reward for Team Science American Association for Cancer Recognizes an outstanding interdisciplinary Recognize team pursuing applied research that may stretch beyond the boundaries of their Award Research research team for innovative and meritorious scientists http://tinyurl.com/38ha78b science that has or will likely advance department and discipline. These challenges can limit professional interest fundamental knowledge of cancer or that in translating research discoveries and hamper the enterprise at a time when it has applied existing knowledge to advance the detection, diagnosis, prevention, or should be expanding to capitalize on the explosion of basic science knowledge. treatment of cancer. Teams are composed In March 2011, the Federation of American Societies for Experimental of independent faculty researchers with Biology (FASEB) organized a symposium to address issues important to basic complementary interdisciplinary expertise, each of whom has made separate scientists choosing to conduct translational research. Attendees examined substantive and quantifi able contributions to the contributions that basic scientists have made and can make in this area, the research. the benefi ts that investigators and institutions derive from participating in Tenure Track Offer National Institutes of Health Provides guidelines for writing letters of Provide guidance translational science, and the unique challenges that basic investigators face in Letter Template: http://tinyurl.com/c38kmu9 offer to, and reviewing and rewarding, on appointing Team and interdisciplinary scientists. It includes interdisciplinary, developing translational research programs. Participants also addressed strategies Interdisciplinary a set of questions to help identify the collaborative to facilitate the involvement of basic scientists in translational research. Science roles, responsibilities, and expectations of researchers scientists and their departments. Benefi ts to Engaging Basic Scientists in Translational Research University of University of California Provides a model for how academic Provide guidance departments and committees can weigh A number of speakers described how basic scientists can benefi t personally Southern California http://tinyurl.com/c2gehxb on rewarding Tenure and interdisciplinary research and collaborative interdisciplinary, and professionally by participating in translational research. They detailed the Promotion Manual scholarship when making tenure and collaborative satisfaction and inspiration that come from working to translate discoveries into promotion decisions. research
treatments and diagnostics for human diseases. Importantly, their involvement GENERAL RESOURCES in clinical applications led to deeper insights into the biological mechanisms they were investigating, led to novel research ideas, enabled them to bring new CTSA Consortium’s CTSA Consortium Provides links to information for basic, Identify research Resources for http://tinyurl.com/6peeoab clinical, and translational research resources research methods into their laboratories, and improved the opportunity to Researchers communities, including research networks, publish. Senior research leaders attending the meeting suggested that biomedical research tools, and funding opportunities available through public and private research institutions also benefi t, because translational research advances their institutions. core mission to enhance human health and well-being, enhances research Team Science National Cancer Institute (NIH) Provides a user-generated collection of Identify research collaboration among their faculty, and helps forge partnerships with industry, Toolkit https://www.teamsciencetoolkit. information and resources that support resources garner additional research funding, and attract trainees. cancer.gov the practice and study of team science. It connects professionals from many disciplines and provides a forum for sharing knowledge and tools.
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FASEB Report Layout.FINAL.indd Spread 4 of 28 - Pages(iv, 47) 3/20/12 5:19 PM Organization Weblink Description Preface TRANSLATIONAL RESEARCH FUNDING National Institute http://nih.gov/ Provides translational research support for basic investigators Basic scientists play a key role in improving human health and treating disease. of Health through investigator-initiated and targeted grants programs for individuals and institutions, as well as opportunities to access Yet despite widespread national interest in accelerating the pace at which resources, instrumentation, and core facilities. Specifi c programs new and improved medical interventions are developed, few initiatives aimed at facilitating translational science are described in the main have focused specifi cally on engaging basic investigators in this process text (Box A). of translation. The Federation of American Societies for Experimental U.S. Department of http://www.research.va.gov/ Provides translational research support for basic and clinical Biology (FASEB), an organization of more than 100,000 researchers— Veterans Affairs VA investigators through investigator-initiated merit review most of whom are basic scientists—seemed to be an excellent place awards and targeted announcements. Investigators can also access translational research resources such as the Clinical to start to address translational research from the vantage point of basic Research Pharmacy and Pharmacogenomics Analysis Laboratory. investigators trained to conduct fundamental biological research. To further Additionally, the VA supports several relevant career development this goal, FASEB held a symposium in March 2011 titled “Engaging Basic programs, including the Career Development Enhancement Award, which provides support for educational leave to learn new research Scientists in Translational Research: Identifying Opportunities, Overcoming skills. Richard Galbraith, Obstacles” to discuss and formulate a set of recommendations for increasing the MD, PhD, Department of http://www.defense.gov/ Provides translational research support to intramural and participation of these investigators in translational science. Defense http://www.darpa.mil/ extramural basic investigators. Extramural programs include the The University of The symposium was sponsored by the Burroughs Wellcome Fund, the U.S. Vermont College of http://cdmrp.army.mil/ Congressionally Directed Medical Research Programs, Defense Department of Veterans Affairs, the Doris Duke Charitable Foundation, the http://dmrdp.fhpr.osd.mil Advanced Research Projects Agency, and the Defense Medical Medicine Research and Development Program. Howard Hughes Medical Institute, and Merck Sharp & Dohme Corp. It attracted approximately 150 people, including representatives from the fi ve sponsoring Nongovernmental, http://www.healthra.org/ Provides grant funding for translational researchers and research Not-for-profi t teams. Many, but not all, of these programs are targeted at specifi c organizations; National Institutes of Health leadership; scientifi c publishers; and organizations diseases, conditions, or biological systems. The Health Research research trainees, junior and senior faculty, department chairs, deans, chancellors, Alliance (see link) is a consortium of 50 such organizations, some and presidents from numerous, diverse academic research institutions. In a mix of which have translational research funding opportunities for basic of lectures, panel presentations, and facilitated group discussions, participants scientists. examined the benefi ts of engaging basic scientists in translational research, the unique challenges these investigators face in carrying out translational research projects, and the ways that the research community could collectively help them to overcome these challenges. In these proceedings, we have attempted to distill the major points emerging from those conversations and to offer a realistic set of recommendations aimed at individual scientists, funding agencies, professional societies, scientifi c publishers, and academic institutions. We hope that this report will inspire and accelerate the critical involvement of basic scientists in translating the fruits of their labor to benefiefi t society.sos cietyy.
Richardhard GaGalbraith,lbraitth MMD,D PPhDhDD Chair, FASEB Translational Research Steering Committee Associate Dean, Patient Oriented Research The University of Vermont College of Medicine
48 Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles Engaging Basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles iii
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