Accepted Manuscript NIDDK Programs and Emerging Opportunities for Digestive Diseases Research Michael J. Grey, Stephen P. James, Griffin P. Rodgers
PII: DOI: Reference:
S0016-5085(15)00341-8 10.1053/j.gastro.2015.03.009 YGAST 59668
To appear in:
Gastroenterology
Please cite this article as: Grey MJ, James SP, Rodgers GP, NIDDK Programs and Emerging Opportunities for Digestive Diseases Research, Gastroenterology (2015), doi: 10.1053/ j.gastro.2015.03.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Gastroenterology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
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NIDDK Programs and Emerging Opportunities for Digestive Diseases Research Michael J. Grey, Stephen P. James1*, Griffin P. Rodgers2 1
Division of Digestive Diseases and Nutrition Office of the Director National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health 9000 Rockville Pike Bethesda, MD 20892 *Corresponding author, email: [email protected]
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NIDDK Mission The National Institutes of Health (NIH) is the largest source of public funding for biomedical research in the United States. Support for research in digestive diseases at NIH is complicated, and the purpose of the commentary is to provide an overview of programs and opportunities for research supported by one of the NIH institutes, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). We encourage interested individuals to use this commentary and the recently revamped NIDDK website (www.niddk.nih.gov) as a starting point for orientation to NIDDK. Interested individuals are strongly encouraged to contact the NIDDK staff directly for further information about their specific ideas and questions (see Table 1 for Program Staff listing).
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The mission of NIDDK is to conduct and support medical research and research training and to disseminate science-based information on diabetes and other endocrine and metabolic diseases; digestive diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases. The Division of Digestive Diseases and Nutrition (DDDN) supports research related to digestive diseases, including the alimentary tract, liver, pancreas, nutrition, and obesity. The programs include basic, translational, and clinical (including therapeutic interventions and outcomes) and population research, research training, and career development. DDDN also promotes public awareness and education about digestive diseases and related conditions. Although NIDDK is one of the primary supporters of research on digestive diseases, other NIH Institutes share this overarching mission as well. Of the $1.6 billion in digestive disease-related funding supported by NIH in Fiscal Year 2014 (based on NIH Research, Condition, and Disease Categorization, http://report.nih.gov/categorical_spending.aspx), approximately 74% comes from three institutes—NIDDK (26.5%), National Cancer Institute (NCI) (29.8%), and National Institute of Allergy and Infectious Diseases (NIAID) (17.7%)—which have distinct but complementary missions in advancing research on digestive diseases. In this commentary we will specifically highlight ongoing programs and emerging opportunities in digestive diseases research within the NIDDK mission. Overview of NIDDK Digestive Diseases Research Portfolio
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The mission of NIDDK is disease and system oriented, and within DDDN, the systems and disease areas of interest include the alimentary GI tract, liver and biliary system, exocrine pancreas, obesity, and nutrition. There are many basic science disciplines that are supported to achieve the mission, including but not limited to cell and molecular biology, developmental and stem cell biology, physiology, genetics and genomics, immunology, inflammation and host defense, microbiology and microbiome, metabolism, and mechanisms of nutrient transport and biology, including metabolomics.
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Digestive diseases research is supported in NIDDK by many different mechanisms (Table 2). These fall into a number of categories: investigator initiated research projects (primarily R01 and R21); large collaborative grants (P01, R24 and U01); clinical trials (U01); research core centers (P30, P50), training (T32), individual fellowship (F30, F31, F32) and career development grants (K01, K08, K23, K24, K99/R00); small business grants (SBIR/STTR). Figure 1 highlights the relative distribution of NIDDK funding across these different categories from fiscal years 2003-2014.
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Investigator-Initiated R01 Portfolio The NIDDK has outlined several core values that we use in guiding our leadership and decision making across all of our Divisions, Offices, and programs (Box 1). Chief among them is to maintain a vigorous investigator-initiated research portfolio. We realize that the innovation and problem-solving of individual investigators is crucial for research progress. As such, NIDDK has strived to maintain funding of investigatorinitiated research project grants at the highest possible level. In NIDDK, about 2/3 of grant funds awarded for research project grants (RPG) are for R01 grants.
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In FY15 we are continuing our strong commitment to fund research project grants. We will maintain the investigator-initiated R01 payline at 13th percentile. R01 applications requesting $500,000 or more have a nominal payline of 8th percentile. To help foster the success of investigators establishing careers in biomedical research, NIDDK will continue to give special consideration to early stage investigators (ESI, defined as new investigators who are within 10 years of completing their terminal degree). For FY2015 ESI R01 applications will be considered for funding with a payline at 18th percentile. In addition, to encourage the stable integration of early career researchers into the biomedical research workforce, NIDDK will set a payline of 15th percentile for the first competing renewal of R01 applications from former NIDDK ESIs (the original application being renewed has to have been an ESI application). Regardless of investigator status, NIDDK will continue to consider interim and limited support in the form of one- or twoyear R56 awards for both new and competing R01 applications that fall over the payline. For more information on the FY2015 NIDDK funding policy, please visit http://www.niddk.nih.gov/research-funding/process/award-funding-policy/Pages/awardfunding-policy.aspx. Collaborative Research Opportunities With many areas of biomedical research becoming increasingly interdisciplinary, NIDDK offers several ways to encourage collaborative research projects. These approaches include multiple-PI R01 grants, program project grants (P01), and interdisciplinary
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collaborative team science grants (R24, resource). These mechanisms differ in administrative and scientific scope (see http://www.niddk.nih.gov/researchfunding/process/apply/about-funding-mechanisms/R24/niddk-collaborative-grantscomparison/Pages/default.aspx)
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The Multiple-PD/PI approach was adopted by NIH as a way to encourage team science approaches. In the context of a multi-PI R01, a team of investigators assume the overall direction and execution of a focused, hypothesis-driven research project. The PIs need to outline and justify the use of the multi-PI format in the context of the scientific goals of the project, and reviewers are asked to consider the complementary and integrated expertise of the PIs as well as the appropriateness of their leadership and governance plan. In FY2014, approximately 12% of all awarded NIDDK R01s in digestive diseases and nutrition used the multi-PI format.
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The Program Project (P01, PAR-13-266) is distinct from the multi-PI R01 in that it involves multiple (R01-like) projects that are built around a unifying central theme. In addition, the research projects should be supported by core facilities. A key element of the program project is that the interrelationships of research projects and collaborations among investigators will yield synergy and results beyond those achievable if each project were pursued independently as in individual R01 grants. It is important that investigators seek DDDN input prior to submission of a proposal.
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A somewhat similar mechanism to the P01 project, but typically without the inclusion of research core components, the collaborative interdisciplinary team science project (R24, PAR-13-305) is designed to bring together collaborative teams to address a single, complex problem related to the NIDDK mission. The team science approach under the R24 can be used to generate a research resource, which may include discovery-based or hypothesis-generating approaches to advance the relevant area of research.
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We strongly encourage all applicants to early on discuss their plans for collaborative P01 and R24 grant applications with program staff. In addition, all R01 applications requesting more than $500,000 in direct costs require NIDDK approval to be accepted.
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Some cooperative studies in basic and translational research use the cooperative agreement U01 award to support a consortium of investigators, in which staff members of NIDDK and other NIH institutes participate. These latter awards are normally solicited by Requests for Applications (RFAs). Clinical studies and trials For clinical studies and trials, if the studies involve not more than 2 investigator sites, the R01 grant award may be used. Studies that are observational and involve multiple centers and have low risk may also use the R01 mechanism. For investigator initiated multicenter clinical trials, the NIDDK uses a sequential approach that normally requires use of a U34 planning grant followed by a separate
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application for the clinical trial (U01). The U34 planning grant provides funding for an investigative team to carry out the numerous tasks that are necessary for implementation of a multi-center clinical trial (see http://www.niddk.nih.gov/researchfunding/process/apply/about-funding-mechanisms/U34/Pages/U34.aspx). This planning grant is intended to support the final stages of clinical trial development, but not for support of preliminary clinical feasibility studies that may be needed to design a clinical trial. For preliminary clinical studies, NIDDK uses the R21 mechanism (see http://grants.nih.gov/grants/guide/pa-files/PA-12-139.html) or the R01 mechanism. Following the planning phase, a separate application is required to fund the clinical trial, using a U01 grant. (see http://www.niddk.nih.gov/researchfunding/process/apply/about-funding-mechanisms/U01/Pages/U01.aspx).
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Many of the current NIDDK supported clinical trial consortia have been solicited by NIDDK through RFAs in which the institute plays a major role in planning the research projects (U01 grants). The current translational and clinical consortia in digestive diseases and nutrition are listed in Table 3. To leverage the Institute’s investments in large research studies, the NIDDK also encourages individuals to submit R01 grant applications that propose collaborative research projects that use resources that are available through collaboration with ongoing large studies (ancillary grant programs). See http://www.niddk.nih.gov/research-funding/process/human-subjects-research/ancillarystudies-major-ongoing-clinical-studies/Pages/examples-parent-studies-ancillarystudies.aspx.
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The NIDDK strongly encourages individuals or groups who are interested in large collaborative studies or clinical trials to contact the NIDDK staff early in their planning process. The different award mechanisms have requirements that are sometimes complicated.
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Emerging Opportunities in Digestive Diseases and Nutrition NIDDK recognizes that different scientific fields may have different needs for support from NIH, reflected in the many different types of ongoing research programs. The institute also is very interested in understanding how new, emerging or underrepresented areas of research might best be harnessed to fulfill the mission of NIDDK. To meet this goal, NIDDK frequently hosts workshops that sometimes result in new program initiatives. The NIDDK also participates in similar workshops and initiatives of other NIH institutes and the NIH Common Fund, which have resulted in important initiatives such as the Human Microbiome Project (http://commonfund.nih.gov/hmp/index) and Metabolomics initiatives (http://commonfund.nih.gov/metabolomics/index). The following are a few examples of recent activities of NIDDK and NIH that are generating new research opportunities. The NIDDK encourages individuals or groups to inform us of their own ideas for important new areas of research that need development. Furthermore, NIDDK staff frequently attend workshops and planning meetings sponsored by other organizations to further
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this aspect of our research mission. Investigators are encouraged to subscribe to updates on NIDDK website for upcoming workshops and forthcoming funding opportunity announcements.
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Chronic Pancreatitis, Diabetes, and Pancreatic Cancer—Following a series of workshops at NIH (1), NIDDK and NCI are partnering to establish a consortium of clinical centers and a data coordinating center to conduct studies on chronic pancreatitis and factors that increase the risk of pancreatic cancer in patients with chronic pancreatitis, pancreatogenic (type 3c) diabetes, or newly diagnosed diabetes. The consortium will undertake comprehensive clinical, epidemiological, and biological characterization of patients with chronic pancreatitis to gain insight into the pathophysiology of chronic pancreatitis and its sequela. The consortium will also establish an annotated repository of biospecimens to allow for the identification and validation of biomarkers for risk stratification and/or early detection. The consortium goals will address key research needs identified by participants of NIDDK- and NCIsponsored workshops. Participants at an NIDDK-sponsored workshop in 2012 stressed the need for further basic and translational research in the area of chronic pancreatitis to identify strategies and therapeutic targets to reduce the burden of disease. In a follow-on workshop sponsored by NIDDK and NCI in 2013, participants highlighted the risk factors that link chronic pancreatitis, diabetes, and pancreatic cancer (2).
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Host-Microbiota Interactions—NIDDK is interested in developing programs to advance research on defining the functional role of the human microbiota in digestive diseases and nutrition. Humans are host to complex microbial communities, and these communities—in particular in the gastrointestinal tract—likely play important roles in many aspects of health and disease. However, in most cases, there is still a lack of understanding of how human-associated microbial communities contribute to disease. In 2014, NIDDK sponsored a workshop to address the key research needs and opportunities for understanding how aspects of host physiology and disease pathophysiology are affected by the microbiota, for interrogating host-microbiota interactions, and for manipulating host-microbiota interactions to modulate disease processes. Workshop participants identified several key themes for areas of future research, including (1) consideration of the bidirectional communication between the host and microbiota and approaches to interrogate the gut microbiota as a critical component of multi-organ physiology; (2) a growing need to move from descriptive studies of composition to identifying and validating the functional components (e.g. secreted bioactive products) of the microbiota and the host pathways they interact with; (3) basic and clinical research to distinguish causative from correlative roles of the human microbiota in disease; and (4) translational research to modulate the functional phenotypes of microbial communities and/or specific host-microbiota interactions as potential therapeutic strategies. Some of these themes can be addressed, at least in part, by R01 applications in response to PAR-13-293 to discover gut microbiota-derived factors in the integrated physiology of NIDDK diseases, as ancillary studies to existing clinical research networks (PAR-12-265), or as pilot clinical studies in digestive diseases and nutrition (R21, PA-12-139). NIDDK is considering additional programs to
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address these key needs for advancing research on host-microbiota interactions in digestive diseases and nutrition.
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Obesity and bariatric surgery research--Emerging evidence suggests that the beneficial effects of bariatric surgery on weight, diabetes and other clinical/metabolic outcomes may extend beyond the physical restrictions of the surgery, malabsorption and the post-operative hypocaloric state. Instead, biological factors and/or molecular targets may be directly altered, influencing food intake, body composition, metabolism of glucose and/or lipids or other unknown factors, ultimately changing the course of metabolic disease. Identifying the mechanisms by which the different surgical procedures (specifically Roux-En-Y gastric bypass and vertical sleeve gastrectomy) and devices exert their beneficial effects is critical in moving forward towards nonsurgical approaches to weight loss, and the treatment of diabetes and other obesityrelated metabolic diseases. Identification of novel targets and pathways within the bariatric surgery model may reveal unrecognized mechanisms that contribute to body adiposity, glucoregulation, lipid metabolism and restoration of b-cell function, all with important therapeutic potential. An initiative to be funded in FY 2015 has been issued to enhance research in this area (http://grants.nih.gov/grants/guide/rfafiles/RFA-DK-14-025.html). The NIDDK also supports a program to identify the long term benefits and risks of bariatric surgery. (http://grants.nih.gov/grants/guide/pafiles/PAR-14-262.html)
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Stimulating Peripheral Activity to Relieve Conditions (SPARC)—The NIH Common Fund-sponsored SPARC program has the central goal of providing a basic understanding of the peripheral nervous system to catalyze development of therapies based on neuromodulation of end-organ system function. Peripheral nerves make connections with and influence the function of every organ in the body. Modulation of peripheral nerve signals to control the functions of the organs they supply has been recognized as a potentially powerful way to treat many diseases and conditions, including gastrointestinal disorders. The SPARC program tentatively plans to support interdisciplinary teams of investigators to deliver neural circuit maps of several organ systems, novel electrode designs, minimally invasive surgical procedures, and stimulation protocols, driven by an end goal to develop new neuromodulation therapies. For more information on the SPARC program, workshops, and funding opportunities, please visit http://commonfund.hin.gov/sparc/. Translational Research for Therapeutic Discovery and Development—As part of our mission to reduce the burden of disease, NIDDK has issued or participates in a series of funding opportunity announcements to encourage the translation of basic discoveries into novel therapeutics for digestive diseases. Figure 2 illustrates a typical pipeline for the discovery and development of small molecules and non-viral biologics that modulate a target or phenotype of interest. As a target or potential therapeutic agent moves through this pipeline the goal is to continue to accumulate evidence that they will modify disease outcomes in clinical populations with acceptable safety profiles. Several FOAs are mapped onto the pipeline to illustrate the specific research challenges they are designed to address at each stage. To help bridge our basic science portfolio with
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goals of therapeutic discovery and development, NIDDK has issued PAR-14-006 to seed collaborations for translational research. The purpose of this announcement is to encourage investigators with active NIDDK R01 research project grants to expand the scope of their current award by submitting a Revision application proposing a new collaboration and specific aim(s) for therapeutic discovery and development (at any stage from target identification in clinical samples through early pre-clinical development). Please visit the NIDDK web site for more information on specific FOAs for therapeutic discovery and development (http://www.niddk.nih.gov/researchfunding/process/translational-research-therapeutic-discoverydevelopment/Pages/default.aspx).
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Research Training and Career Development Programs NIDDK has a robust group of programs that support research training and career development. NIDDK participates in many of the NIH wide programs, which include programs to support training of medical and graduate students, postdoctoral fellows, and physician scientists through institutional and individual grants. (see http://www.niddk.nih.gov/research-funding/training-careerdevelopment/Pages/default.aspx).
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Additional financial assistance for early stage investigators is also available from NIDDK through the NIH loan repayment program for clinical research and pediatric research (http://www.lrp.nih.gov/index.aspx). This is an important mechanism for NIDDK to assure support to trainees considering an academic career in clinically related research by providing a two-year (renewable) loan repayment to offset debt related to medical or other professional school expenses.
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Small Business Product Development and Commercialization The NIDDK Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs support innovative research conducted by small businesses that has the potential for commercialization. The funds for this program are set-aside and therefore do not compete with the regular research, training, or other special programs supported by NIDDK. The amount of funds set aside is likely to increase over the next few years, and applicant success rates are high for this type of funding. NIDDK participates in the NIH-wide omnibus FOAs for SBIR (R43/R44, PA-14071) and STTR mechanisms (R41/R42, PA-14-072). In addition, NIDDK participates in targeted SBIR/STTR announcements related to new tools for the study of lymphatics in the digestive system (PA-12-258), development of new technologies for viral hepatitis (PA-15-076, PA-15-077), and lead optimization and pre-clinical development of therapeutic candidates (PA-14-054, PA-14-055). Please visit the NIDDK Small Business Program website for more information on SBIR/STTR grant mechanisms, eligibility, and topic areas of interest in digestive diseases and nutrition (http://www.niddk.nih.gov/research-funding/process/small-business/Pages/smallbusiness-programs.aspx).
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Research Resources for Digestive Diseases Research Core Centers Center Core Grants (P30) support shared resources and facilities for use by multiple investigators to enhance multidisciplinary approaches and collaborative research efforts focused on a common research problem(s) or goal(s) within an institution or across institutions (see Table 4). The core grant mechanism provides enabling technology and infrastructure that enhance work by independently funded research projects. Digestive Disease Research Core Centers (DDRCCs) provide a mechanism for funding shared resources (core facilities) that serve to integrate, coordinate, and foster interdisciplinary cooperation between groups of established investigators who conduct programs of high quality research that are related to a common theme in digestive diseases research. In addition, these centers provide pilot seed funding for new research initiatives (particularly by early stage investigators) relevant to the themes of the center. An existing base of high quality digestive disease-related research is a prerequisite for the establishment of a center. The research emphases of centers in this program presently focus on liver diseases, gastrointestinal motility, absorption and secretion processes, inflammatory bowel disease, structure/function relationships in the gastrointestinal tract, neuropeptides and gut hormones, and gastrointestinal membrane receptors. (see http://www.niddk.nih.gov/research-funding/research-programs/Pages/digestive-diseasecenters.aspx).
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In collaboration with the NIH Office of Research on Women’s Health, NIDDK co-funds one specialized center of research (SPOR, P50) at the University of California Los Angeles, the Center for Neurovisceral Sciences & Women’s Health (Emeran Meyer, principal investigator), which focuses on understanding sex differences in stress response systems in visceral pain.
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In addition, NIDDK currently supports 12 nutrition obesity research centers which historically used to be distinct as nutrition or obesity centers and now they are merged. These programs are expected to bring together established and new investigators who are actively conducting high-quality research programs related to common nutritional sciences and/or obesity theme(s) and to improve the quality and multidisciplinary nature of research in nutritional sciences and/or obesity by providing shared access to specialized technical resources and expertise (see http://www.niddk.nih.gov/researchfunding/research-programs/Pages/nutrition-obesity-centers.aspx). The goals and organization of these centers are philosophically aligned with those of the DDRCCs described above. NIDDK Central Repository The NIDDK provides access to reagents, data, DNA and biospecimens through the NIDDK Central Repository (see https://www.niddkrepository.org/home/). The data and samples have been collected for over a decade from many of the large studies that have been sponsored by NIDDK. There is a relatively straightforward application process to obtain access to these resources. In addition, the NIDDK web site has a detailed listing of various studies and resources that are available to the NIDDK
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community (http://www.niddk.nih.gov/research-funding/researchresources/Pages/default.aspx).
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In conclusion, NIDDK is committed to advancing the mission of supporting research in digestive and liver disease, to support public awareness and education and ultimately to improve health. We welcome input and suggestions from the academic community, particularly in developing workshops as new or emerging areas of interest arise.
References
Pasca di Magliano M, Forsmark C, Freedman S, Hebrok M, Pasricha PJ, Saluja A, Stanger BZ, Holt J, Serrano J, James SP, Rustgi AK. Gastroenterology. 2013;144:e1-4
2.
Andersen DK1, Andren-Sandberg Å, Duell EJ, Goggins M, Korc M, Petersen GM, Smith JP, Whitcomb DC. Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop. Pancreas. 2013;42:1227-37
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Box 1. NIDDK Mission and Core Values The mission of the NIDDK is to conduct and support medical research and research training and to disseminate science-based information on diabetes and other endocrine and metabolic diseases; digestive diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases, to improve people’s health and quality of life. NIDDK will pursue the most compelling research to combat the many debilitating and costly chronic diseases within our mission. We will remain firmly committed to basic, translational, and clinical research; research training and career development; and dissemination of health information to improve the lives of patients, their families, and those at risk for these diseases. NIDDK leadership uses the following overarching principles to guide decision making to fulfill our mission.
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Maintain a Vigorous Investigator-Initiated Research Portfolio: The innovativeness and problem solving of individual investigators are crucial for research progress. Therefore, the NIDDK will maintain funding of investigator-initiated grants at the highest possible level. We will also maximize our investments by supporting cross-cutting science that is broadly applicable to many disease-specific research issues.
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Supporting Pivotal Clinical Studies and Trials: Clinical studies will continue to be an integral component of research on the broad spectrum of diseases for which NIDDK has research responsibility. Because many of these diseases disproportionately affect minority populations, we will continue to seek insights and answers to health disparities. We are also maximizing our investments by expanding the investigative community's access to very valuable research resources accrued in our major clinical trials. We are doing this by funding ancillary studies to these trials and by supporting a central repository for biologic materials from clinical trials.
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Preserve a Stable Pool of Talented New Investigators: The ideas and fresh perspectives of new investigators invigorate the research community. Thus, we will strive to ensure that new investigators can realize their potential for contributing to biomedical research, and that today's generation of young scientists will view research as a viable career. We will foster mentorship of new investigators, and promote special consideration for funding of talented new investigators.
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Foster Exceptional Research Training and Mentoring Opportunities: Maintaining an NIDDK-focused pipeline of outstanding investigators is critically important to our research progress. We will continue to support significant opportunities at the graduatestudent and postdoctoral levels, as well as through research career development awards, and undergraduate research educational opportunities. Ensure Knowledge Dissemination through Outreach and Communication: We are continuing efforts to ensure that the science-based knowledge gained from NIDDKfunded research is imparted to health care providers and the public for the direct benefit of patients and their families.
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Table 1. Program Staff, Division of Digestive Diseases and Nutrition, NIDDK Name
Title
Contact Information
Program Area
Program
Observational and Investigational Clinical Research;
[email protected]
Dana
Director
Biomedical Devices, Surgical Interventions, and Medications
301-594-8879
Program Director
Basic Neurogastroenterology; Gastrointestinal Development, [email protected] Epithelial Biology, Stem Cell Biology, and Inflammation 301-402-0671
Densmore,
Program
Institutional Training; Small Business Technology
Christine
Director
Development
[email protected] 301-402-8714
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Carrington, Jill
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Andersen,
Fatty Liver Disease; Genetic Liver Disease; HIV and Liver; Program Doo, Edward
Cell Injury, Repair, Fibrosis, and Inflammation; Pediatric Liver Director
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Disease; Viral Hepatitis and Infectious Diseases
[email protected] 301-451-4524
Special Projects in Nutrition, Obesity, and Digestive Diseases; Program Evans, Mary
Lifestyle Interventions in Obesity; Nutrition Obesity Research Director
Centers; Diet & Physical Activity Assessment Methodology Clinical
Hall, Sherry trials
[email protected] 301-594-4578
[email protected]
Clinical trials specialist, supporting multi-center clinical trials
specialist
301-435-8150
Program
Frank
Director
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Gastrointestinal and Nutrition AIDS; Gastrointestinal Hamilton,
Endoscopy Research; Gastrointestinal Mucosa and Immunology; Gastrointestinal Motility
Hoofnagle,
Deputy
Jay
Director
James,
Division
Stephen
Director
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Basic and Clinical Research on Liver Diseases
Oversight of DDDN Programs
Director
Kuczmarski,
Program
Robert
Director
Obesity Prevention and Treatment
Maruvada,
Program
Padma
Director
301-594-8877 [email protected] 301-496-1333 [email protected]
301-594-7680
Genetics, Genomics, and Microbiome Studies of the GI Tract, [email protected] Liver, and Pancreatic Diseases, Nutrition, and Obesity 301-451-8875
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Program
Karp, Robert
[email protected]
Nutrient Metabolism; Clinical Obesity and Nutrition
[email protected] 301-451-8354 [email protected] 301-594-8884
Program
Gastrointestinal Host-Microbial Interactions, Basic Mucosal
[email protected]
Director
Immunology and Inflammation
301-451-3759
Perrin, Peter
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Digestive Diseases Research Centers; Digestive Diseases Podskalny,
Program
Judith
Director
and Nutrition Career Development and Fellowships; Loan
[email protected] 301-594-8876
Repayment Program Liver Bioengineering and Biotechnology; Cell and Molecular Program
Biology of the Liver; Developmental Biology and
Director
Regeneration; Drug-induced Liver Disease; Gastrointestinal Neuroendocrinology; Exocrine Pancreas; Pancreatitis
[email protected]
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Serrano, Jose
301-594-8871
Autoimmune Liver Disease; Acute Liver Failure; Bile, Bilirubin Program
and Cholestasis; Complications of Chronic Liver Disease;
[email protected]
Averell
Director
Gallbladder and Biliary Diseases; Liver Cancer; Liver
301-451-6207
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Sherker,
Transplantation
Torrance,
Clinical
Rebecca
Trialist
Unalp-Arida,
Program
Epidemiology, Clinical Trials, Digestive Diseases, and
[email protected]
Aynur
Director
Nutrition
301-594-8879
Clinical
Clinical trials specialist, supporting multi-center clinical trials
[email protected]
Trialist
PLEASE ADD A DESCRPITOR
+1 301 594 0056
Van
Raaphorst, Rebekah
Yanovski,
Program
Susan
Director
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Clinical trials specialist, supporting multi-center clinical trials
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Obesity and Eating Disorders
[email protected]
301-594-7024
[email protected] 301-594-8882
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Table 2: NIDDK supports digestive diseases research through many different types of grants* Investigator initiated projects: R01, R03, R15, R18, R21
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Large research programs (P01, R24, U01, U54) Clinical studies and trials (U34, U01) Research Centers (P30, P50)
Small business (R41, R42, R43, R44)
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Conferences, curriculum, others (R13, R25)
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Fellowship, institutional training, and career development (F, T and K grants)
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*Most common grant types: there are others for special purposes that are typically part of special announcements
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Table 3. Translational and Clinical Research Studies Supported by Division of Digestive Diseases and Nutrition, NIDDK Study Name Study website Gastrointestinal Gastroparesis Research http://jhuccs1.us/gpcrc/ Consortium IBD Genetics Consortium http://ibdgc.uchicago.edu/ Intestinal Stem Cell https://iscconsortium.org/ Consortium* Self-Administered CBT for http://ubbmc.buffalo.edu/research/ibsos.php IBS MERIT UC http://merit.web.unc.edu/ PROTECT UC http://www.cscc.unc.edu/protect/ Probiotics to Reduce the Website is not available Incidence of Diarrhea and Enteropathy in Children in Peru (PRIDEC-Peru) Liver Hepatitis B Clinical http://www.hepbnet.org/ Research Network Acute Liver Failure www.utsouthwestern.edu/labs/acute-liver/about/ Pediatric Acute Liver www.palfstudy.org/ Failure Network Childhood Liver Disease www.childrennetwork.org/ Research and Education Network (ChiLDREN) Drug Induced Liver Injury https://dilin.dcri.duke.edu/ Network (DILIN) Nonalcoholic https://jhuccs1.us/nash Steatohepatitis (NASH) Clinical Research Network Obesity Life Moms https://lifemoms.bsc.gwu.edu/web/lifemoms/home?p_p_id =58&p_p_lifecycle=0&_58_redirect=/ Look AHEAD http://www.lookaheadtrial.org/public/home.cfm Teen-LABS http://www.cincinnatichildrens.org/research/divisions/t/teen -labs/default/ *Basic research network that includes research aims involving human subjects
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Table 4. Digestive Disease Research Core Centers and Nutrition and Obesity Research Centers
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See attached Excel spreadsheet
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Figure 1. NIDDK Extramural Research Funding by Category (Competing and Noncompeting). The relative funding levels of NIDDK extramural research categories are shown for fiscal years 2003-2014. The relative funding levels for each category have remained fairly stable since FY2003. These data support the NIDDK core values to maintain a strong investigator-initiated R01 program, preserve a stable pool of talented new investigators, support key clinical studies and trials, and continue strong support of training and career development programs.
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Figure 2: Funding Opportunity Announcements to Support Translational Research for Therapeutic Discovery and Development. This figure illustrates a “translational pipeline” for the development of novel therapeutics. The different stages of therapeutic discovery and development are labeled across the top of the pipeline. The horizontal bars (in blue) are labeled with funding opportunity announcements that are designed to address key research needs/challenges for the indicated stages covered by the width of the bar. For more information on each stage and specific funding opportunity announcements, please visit: http://www.niddk.nih.gov/researchfunding/process/translational-research-therapeutic-discoverydevelopment/Pages/default.aspx.
NIDDK Division of Digestive Diseases and Nutrition Research Centers (P30)
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Institution
Principal Investigator
Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Diseases
Digestive Diseases Research Centers (P30)
Mayo Center for Cell Signaling in Gastroenterology Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Diseases Center for Gastrointestinal Biology and Disease CURE: Digestive Diseases Research Center Silvio O. Conte Digestive Diseases Research Core Centers Center for GI Infection and Inujury USC Research Center for Liver Disease Regulatory Factors in the GI Tract
Mayo Clinic Rochester Cincinnati Childrens Hospital Medical Center U. of North Carolina Chapel Hill U. of California Los Angeles
Jorge Bezerra Robert Sandler Juan Rozengurt Michael Nathanson Hashem El-Serag Neil Kaplowitz Nicholas Davidson
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Yale University Baylor College of Medicine U. of Southern California Washington University
Nicholas LaRusso
Vanderbilt University U. of Pennsylvania Albert Einstein college of Medicine U. of Chicago U. of Michigan
Richard Peek Anil Rustgi
Centr for the Study of Inflammatory Bowel Disease UCSF Liver Core Center Hopkins Digestive Diseases Basic and Translatoinal Research Core Center Integrated Epithelial and Mucosal Biology Cleveland Digestive Diseases Research Core Center
Ramnik Xavier Jacquelyn Maher
Allan Wolkoff
Eugene Chang Chung Owyang
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Massachusetts General Hospital U. of California San Francisco
Molecular and Cellular Basis for Digestive Diseases Center for Digestive and Liver Diseases Liver Pathobiology and Gene Therapy Research Core Center IBD and Mucosal Inflammation, Immunology and Microbiology of the GI Tract Gastrointestinal Hormone Research Core Center
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Johns Hopkins University Children's Hospital Corporation Boston Case Western Reserve University
Obesity Nutrition Research Centers U. of Alabama at Birmingham U. of North Carolina Chapel Hill
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LSU Pennington Biomedical Research Center Massachusetts General Hospital U. of Minnesota
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Washington University Boston Medical Center U. of Colorado Denver U. of Washington Columbia University U. of Michigan U. of Maryland Baltimore
UAB Nutrition Obesity Research Center UNC-CH Nutrition Obesity Research Center Washington University Nutrition Obesity Research Center Boston Nutrition Obesity Research Center Colorado Nutrition Obesity Research Center Nutrition Obesity Research Center New York Nutrition Obesity Research Center Nutrition and Obesity Research Center Mid-Atlantic Nutritoin Obesity Research Center Nutritional Programming: Environmental and molecular Interactions Nutrition Obesity Research Center at Harvard Minnesota Obesity Center
Mark Donowitz Wayne Lencer Fabio Cominelli
David Allison Steven Zeisel
Samuel Klein Susan Fried James O. Hill Michael Schwartz Xavier Pi-Sunyer Charles F. Burant Alan Shuldiner Eric Ravussin Allan Walker Allen Levine
PII: DOI: Reference:
S0016-5085(15)00341-8 10.1053/j.gastro.2015.03.009 YGAST 59668
To appear in:
Gastroenterology
Please cite this article as: Grey MJ, James SP, Rodgers GP, NIDDK Programs and Emerging Opportunities for Digestive Diseases Research, Gastroenterology (2015), doi: 10.1053/ j.gastro.2015.03.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. All studies published in Gastroenterology are embargoed until 3PM ET of the day they are published as corrected proofs on-line. Studies cannot be publicized as accepted manuscripts or uncorrected proofs.
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NIDDK Programs and Emerging Opportunities for Digestive Diseases Research Michael J. Grey, Stephen P. James1*, Griffin P. Rodgers2 1
Division of Digestive Diseases and Nutrition Office of the Director National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health 9000 Rockville Pike Bethesda, MD 20892 *Corresponding author, email: [email protected]
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NIDDK Mission The National Institutes of Health (NIH) is the largest source of public funding for biomedical research in the United States. Support for research in digestive diseases at NIH is complicated, and the purpose of the commentary is to provide an overview of programs and opportunities for research supported by one of the NIH institutes, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). We encourage interested individuals to use this commentary and the recently revamped NIDDK website (www.niddk.nih.gov) as a starting point for orientation to NIDDK. Interested individuals are strongly encouraged to contact the NIDDK staff directly for further information about their specific ideas and questions (see Table 1 for Program Staff listing).
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The mission of NIDDK is to conduct and support medical research and research training and to disseminate science-based information on diabetes and other endocrine and metabolic diseases; digestive diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases. The Division of Digestive Diseases and Nutrition (DDDN) supports research related to digestive diseases, including the alimentary tract, liver, pancreas, nutrition, and obesity. The programs include basic, translational, and clinical (including therapeutic interventions and outcomes) and population research, research training, and career development. DDDN also promotes public awareness and education about digestive diseases and related conditions. Although NIDDK is one of the primary supporters of research on digestive diseases, other NIH Institutes share this overarching mission as well. Of the $1.6 billion in digestive disease-related funding supported by NIH in Fiscal Year 2014 (based on NIH Research, Condition, and Disease Categorization, http://report.nih.gov/categorical_spending.aspx), approximately 74% comes from three institutes—NIDDK (26.5%), National Cancer Institute (NCI) (29.8%), and National Institute of Allergy and Infectious Diseases (NIAID) (17.7%)—which have distinct but complementary missions in advancing research on digestive diseases. In this commentary we will specifically highlight ongoing programs and emerging opportunities in digestive diseases research within the NIDDK mission. Overview of NIDDK Digestive Diseases Research Portfolio
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The mission of NIDDK is disease and system oriented, and within DDDN, the systems and disease areas of interest include the alimentary GI tract, liver and biliary system, exocrine pancreas, obesity, and nutrition. There are many basic science disciplines that are supported to achieve the mission, including but not limited to cell and molecular biology, developmental and stem cell biology, physiology, genetics and genomics, immunology, inflammation and host defense, microbiology and microbiome, metabolism, and mechanisms of nutrient transport and biology, including metabolomics.
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Digestive diseases research is supported in NIDDK by many different mechanisms (Table 2). These fall into a number of categories: investigator initiated research projects (primarily R01 and R21); large collaborative grants (P01, R24 and U01); clinical trials (U01); research core centers (P30, P50), training (T32), individual fellowship (F30, F31, F32) and career development grants (K01, K08, K23, K24, K99/R00); small business grants (SBIR/STTR). Figure 1 highlights the relative distribution of NIDDK funding across these different categories from fiscal years 2003-2014.
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Investigator-Initiated R01 Portfolio The NIDDK has outlined several core values that we use in guiding our leadership and decision making across all of our Divisions, Offices, and programs (Box 1). Chief among them is to maintain a vigorous investigator-initiated research portfolio. We realize that the innovation and problem-solving of individual investigators is crucial for research progress. As such, NIDDK has strived to maintain funding of investigatorinitiated research project grants at the highest possible level. In NIDDK, about 2/3 of grant funds awarded for research project grants (RPG) are for R01 grants.
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In FY15 we are continuing our strong commitment to fund research project grants. We will maintain the investigator-initiated R01 payline at 13th percentile. R01 applications requesting $500,000 or more have a nominal payline of 8th percentile. To help foster the success of investigators establishing careers in biomedical research, NIDDK will continue to give special consideration to early stage investigators (ESI, defined as new investigators who are within 10 years of completing their terminal degree). For FY2015 ESI R01 applications will be considered for funding with a payline at 18th percentile. In addition, to encourage the stable integration of early career researchers into the biomedical research workforce, NIDDK will set a payline of 15th percentile for the first competing renewal of R01 applications from former NIDDK ESIs (the original application being renewed has to have been an ESI application). Regardless of investigator status, NIDDK will continue to consider interim and limited support in the form of one- or twoyear R56 awards for both new and competing R01 applications that fall over the payline. For more information on the FY2015 NIDDK funding policy, please visit http://www.niddk.nih.gov/research-funding/process/award-funding-policy/Pages/awardfunding-policy.aspx. Collaborative Research Opportunities With many areas of biomedical research becoming increasingly interdisciplinary, NIDDK offers several ways to encourage collaborative research projects. These approaches include multiple-PI R01 grants, program project grants (P01), and interdisciplinary
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collaborative team science grants (R24, resource). These mechanisms differ in administrative and scientific scope (see http://www.niddk.nih.gov/researchfunding/process/apply/about-funding-mechanisms/R24/niddk-collaborative-grantscomparison/Pages/default.aspx)
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The Multiple-PD/PI approach was adopted by NIH as a way to encourage team science approaches. In the context of a multi-PI R01, a team of investigators assume the overall direction and execution of a focused, hypothesis-driven research project. The PIs need to outline and justify the use of the multi-PI format in the context of the scientific goals of the project, and reviewers are asked to consider the complementary and integrated expertise of the PIs as well as the appropriateness of their leadership and governance plan. In FY2014, approximately 12% of all awarded NIDDK R01s in digestive diseases and nutrition used the multi-PI format.
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The Program Project (P01, PAR-13-266) is distinct from the multi-PI R01 in that it involves multiple (R01-like) projects that are built around a unifying central theme. In addition, the research projects should be supported by core facilities. A key element of the program project is that the interrelationships of research projects and collaborations among investigators will yield synergy and results beyond those achievable if each project were pursued independently as in individual R01 grants. It is important that investigators seek DDDN input prior to submission of a proposal.
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A somewhat similar mechanism to the P01 project, but typically without the inclusion of research core components, the collaborative interdisciplinary team science project (R24, PAR-13-305) is designed to bring together collaborative teams to address a single, complex problem related to the NIDDK mission. The team science approach under the R24 can be used to generate a research resource, which may include discovery-based or hypothesis-generating approaches to advance the relevant area of research.
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We strongly encourage all applicants to early on discuss their plans for collaborative P01 and R24 grant applications with program staff. In addition, all R01 applications requesting more than $500,000 in direct costs require NIDDK approval to be accepted.
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Some cooperative studies in basic and translational research use the cooperative agreement U01 award to support a consortium of investigators, in which staff members of NIDDK and other NIH institutes participate. These latter awards are normally solicited by Requests for Applications (RFAs). Clinical studies and trials For clinical studies and trials, if the studies involve not more than 2 investigator sites, the R01 grant award may be used. Studies that are observational and involve multiple centers and have low risk may also use the R01 mechanism. For investigator initiated multicenter clinical trials, the NIDDK uses a sequential approach that normally requires use of a U34 planning grant followed by a separate
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application for the clinical trial (U01). The U34 planning grant provides funding for an investigative team to carry out the numerous tasks that are necessary for implementation of a multi-center clinical trial (see http://www.niddk.nih.gov/researchfunding/process/apply/about-funding-mechanisms/U34/Pages/U34.aspx). This planning grant is intended to support the final stages of clinical trial development, but not for support of preliminary clinical feasibility studies that may be needed to design a clinical trial. For preliminary clinical studies, NIDDK uses the R21 mechanism (see http://grants.nih.gov/grants/guide/pa-files/PA-12-139.html) or the R01 mechanism. Following the planning phase, a separate application is required to fund the clinical trial, using a U01 grant. (see http://www.niddk.nih.gov/researchfunding/process/apply/about-funding-mechanisms/U01/Pages/U01.aspx).
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Many of the current NIDDK supported clinical trial consortia have been solicited by NIDDK through RFAs in which the institute plays a major role in planning the research projects (U01 grants). The current translational and clinical consortia in digestive diseases and nutrition are listed in Table 3. To leverage the Institute’s investments in large research studies, the NIDDK also encourages individuals to submit R01 grant applications that propose collaborative research projects that use resources that are available through collaboration with ongoing large studies (ancillary grant programs). See http://www.niddk.nih.gov/research-funding/process/human-subjects-research/ancillarystudies-major-ongoing-clinical-studies/Pages/examples-parent-studies-ancillarystudies.aspx.
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The NIDDK strongly encourages individuals or groups who are interested in large collaborative studies or clinical trials to contact the NIDDK staff early in their planning process. The different award mechanisms have requirements that are sometimes complicated.
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Emerging Opportunities in Digestive Diseases and Nutrition NIDDK recognizes that different scientific fields may have different needs for support from NIH, reflected in the many different types of ongoing research programs. The institute also is very interested in understanding how new, emerging or underrepresented areas of research might best be harnessed to fulfill the mission of NIDDK. To meet this goal, NIDDK frequently hosts workshops that sometimes result in new program initiatives. The NIDDK also participates in similar workshops and initiatives of other NIH institutes and the NIH Common Fund, which have resulted in important initiatives such as the Human Microbiome Project (http://commonfund.nih.gov/hmp/index) and Metabolomics initiatives (http://commonfund.nih.gov/metabolomics/index). The following are a few examples of recent activities of NIDDK and NIH that are generating new research opportunities. The NIDDK encourages individuals or groups to inform us of their own ideas for important new areas of research that need development. Furthermore, NIDDK staff frequently attend workshops and planning meetings sponsored by other organizations to further
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this aspect of our research mission. Investigators are encouraged to subscribe to updates on NIDDK website for upcoming workshops and forthcoming funding opportunity announcements.
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Chronic Pancreatitis, Diabetes, and Pancreatic Cancer—Following a series of workshops at NIH (1), NIDDK and NCI are partnering to establish a consortium of clinical centers and a data coordinating center to conduct studies on chronic pancreatitis and factors that increase the risk of pancreatic cancer in patients with chronic pancreatitis, pancreatogenic (type 3c) diabetes, or newly diagnosed diabetes. The consortium will undertake comprehensive clinical, epidemiological, and biological characterization of patients with chronic pancreatitis to gain insight into the pathophysiology of chronic pancreatitis and its sequela. The consortium will also establish an annotated repository of biospecimens to allow for the identification and validation of biomarkers for risk stratification and/or early detection. The consortium goals will address key research needs identified by participants of NIDDK- and NCIsponsored workshops. Participants at an NIDDK-sponsored workshop in 2012 stressed the need for further basic and translational research in the area of chronic pancreatitis to identify strategies and therapeutic targets to reduce the burden of disease. In a follow-on workshop sponsored by NIDDK and NCI in 2013, participants highlighted the risk factors that link chronic pancreatitis, diabetes, and pancreatic cancer (2).
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Host-Microbiota Interactions—NIDDK is interested in developing programs to advance research on defining the functional role of the human microbiota in digestive diseases and nutrition. Humans are host to complex microbial communities, and these communities—in particular in the gastrointestinal tract—likely play important roles in many aspects of health and disease. However, in most cases, there is still a lack of understanding of how human-associated microbial communities contribute to disease. In 2014, NIDDK sponsored a workshop to address the key research needs and opportunities for understanding how aspects of host physiology and disease pathophysiology are affected by the microbiota, for interrogating host-microbiota interactions, and for manipulating host-microbiota interactions to modulate disease processes. Workshop participants identified several key themes for areas of future research, including (1) consideration of the bidirectional communication between the host and microbiota and approaches to interrogate the gut microbiota as a critical component of multi-organ physiology; (2) a growing need to move from descriptive studies of composition to identifying and validating the functional components (e.g. secreted bioactive products) of the microbiota and the host pathways they interact with; (3) basic and clinical research to distinguish causative from correlative roles of the human microbiota in disease; and (4) translational research to modulate the functional phenotypes of microbial communities and/or specific host-microbiota interactions as potential therapeutic strategies. Some of these themes can be addressed, at least in part, by R01 applications in response to PAR-13-293 to discover gut microbiota-derived factors in the integrated physiology of NIDDK diseases, as ancillary studies to existing clinical research networks (PAR-12-265), or as pilot clinical studies in digestive diseases and nutrition (R21, PA-12-139). NIDDK is considering additional programs to
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address these key needs for advancing research on host-microbiota interactions in digestive diseases and nutrition.
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Obesity and bariatric surgery research--Emerging evidence suggests that the beneficial effects of bariatric surgery on weight, diabetes and other clinical/metabolic outcomes may extend beyond the physical restrictions of the surgery, malabsorption and the post-operative hypocaloric state. Instead, biological factors and/or molecular targets may be directly altered, influencing food intake, body composition, metabolism of glucose and/or lipids or other unknown factors, ultimately changing the course of metabolic disease. Identifying the mechanisms by which the different surgical procedures (specifically Roux-En-Y gastric bypass and vertical sleeve gastrectomy) and devices exert their beneficial effects is critical in moving forward towards nonsurgical approaches to weight loss, and the treatment of diabetes and other obesityrelated metabolic diseases. Identification of novel targets and pathways within the bariatric surgery model may reveal unrecognized mechanisms that contribute to body adiposity, glucoregulation, lipid metabolism and restoration of b-cell function, all with important therapeutic potential. An initiative to be funded in FY 2015 has been issued to enhance research in this area (http://grants.nih.gov/grants/guide/rfafiles/RFA-DK-14-025.html). The NIDDK also supports a program to identify the long term benefits and risks of bariatric surgery. (http://grants.nih.gov/grants/guide/pafiles/PAR-14-262.html)
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Stimulating Peripheral Activity to Relieve Conditions (SPARC)—The NIH Common Fund-sponsored SPARC program has the central goal of providing a basic understanding of the peripheral nervous system to catalyze development of therapies based on neuromodulation of end-organ system function. Peripheral nerves make connections with and influence the function of every organ in the body. Modulation of peripheral nerve signals to control the functions of the organs they supply has been recognized as a potentially powerful way to treat many diseases and conditions, including gastrointestinal disorders. The SPARC program tentatively plans to support interdisciplinary teams of investigators to deliver neural circuit maps of several organ systems, novel electrode designs, minimally invasive surgical procedures, and stimulation protocols, driven by an end goal to develop new neuromodulation therapies. For more information on the SPARC program, workshops, and funding opportunities, please visit http://commonfund.hin.gov/sparc/. Translational Research for Therapeutic Discovery and Development—As part of our mission to reduce the burden of disease, NIDDK has issued or participates in a series of funding opportunity announcements to encourage the translation of basic discoveries into novel therapeutics for digestive diseases. Figure 2 illustrates a typical pipeline for the discovery and development of small molecules and non-viral biologics that modulate a target or phenotype of interest. As a target or potential therapeutic agent moves through this pipeline the goal is to continue to accumulate evidence that they will modify disease outcomes in clinical populations with acceptable safety profiles. Several FOAs are mapped onto the pipeline to illustrate the specific research challenges they are designed to address at each stage. To help bridge our basic science portfolio with
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goals of therapeutic discovery and development, NIDDK has issued PAR-14-006 to seed collaborations for translational research. The purpose of this announcement is to encourage investigators with active NIDDK R01 research project grants to expand the scope of their current award by submitting a Revision application proposing a new collaboration and specific aim(s) for therapeutic discovery and development (at any stage from target identification in clinical samples through early pre-clinical development). Please visit the NIDDK web site for more information on specific FOAs for therapeutic discovery and development (http://www.niddk.nih.gov/researchfunding/process/translational-research-therapeutic-discoverydevelopment/Pages/default.aspx).
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Research Training and Career Development Programs NIDDK has a robust group of programs that support research training and career development. NIDDK participates in many of the NIH wide programs, which include programs to support training of medical and graduate students, postdoctoral fellows, and physician scientists through institutional and individual grants. (see http://www.niddk.nih.gov/research-funding/training-careerdevelopment/Pages/default.aspx).
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Additional financial assistance for early stage investigators is also available from NIDDK through the NIH loan repayment program for clinical research and pediatric research (http://www.lrp.nih.gov/index.aspx). This is an important mechanism for NIDDK to assure support to trainees considering an academic career in clinically related research by providing a two-year (renewable) loan repayment to offset debt related to medical or other professional school expenses.
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Small Business Product Development and Commercialization The NIDDK Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs support innovative research conducted by small businesses that has the potential for commercialization. The funds for this program are set-aside and therefore do not compete with the regular research, training, or other special programs supported by NIDDK. The amount of funds set aside is likely to increase over the next few years, and applicant success rates are high for this type of funding. NIDDK participates in the NIH-wide omnibus FOAs for SBIR (R43/R44, PA-14071) and STTR mechanisms (R41/R42, PA-14-072). In addition, NIDDK participates in targeted SBIR/STTR announcements related to new tools for the study of lymphatics in the digestive system (PA-12-258), development of new technologies for viral hepatitis (PA-15-076, PA-15-077), and lead optimization and pre-clinical development of therapeutic candidates (PA-14-054, PA-14-055). Please visit the NIDDK Small Business Program website for more information on SBIR/STTR grant mechanisms, eligibility, and topic areas of interest in digestive diseases and nutrition (http://www.niddk.nih.gov/research-funding/process/small-business/Pages/smallbusiness-programs.aspx).
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Research Resources for Digestive Diseases Research Core Centers Center Core Grants (P30) support shared resources and facilities for use by multiple investigators to enhance multidisciplinary approaches and collaborative research efforts focused on a common research problem(s) or goal(s) within an institution or across institutions (see Table 4). The core grant mechanism provides enabling technology and infrastructure that enhance work by independently funded research projects. Digestive Disease Research Core Centers (DDRCCs) provide a mechanism for funding shared resources (core facilities) that serve to integrate, coordinate, and foster interdisciplinary cooperation between groups of established investigators who conduct programs of high quality research that are related to a common theme in digestive diseases research. In addition, these centers provide pilot seed funding for new research initiatives (particularly by early stage investigators) relevant to the themes of the center. An existing base of high quality digestive disease-related research is a prerequisite for the establishment of a center. The research emphases of centers in this program presently focus on liver diseases, gastrointestinal motility, absorption and secretion processes, inflammatory bowel disease, structure/function relationships in the gastrointestinal tract, neuropeptides and gut hormones, and gastrointestinal membrane receptors. (see http://www.niddk.nih.gov/research-funding/research-programs/Pages/digestive-diseasecenters.aspx).
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In collaboration with the NIH Office of Research on Women’s Health, NIDDK co-funds one specialized center of research (SPOR, P50) at the University of California Los Angeles, the Center for Neurovisceral Sciences & Women’s Health (Emeran Meyer, principal investigator), which focuses on understanding sex differences in stress response systems in visceral pain.
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In addition, NIDDK currently supports 12 nutrition obesity research centers which historically used to be distinct as nutrition or obesity centers and now they are merged. These programs are expected to bring together established and new investigators who are actively conducting high-quality research programs related to common nutritional sciences and/or obesity theme(s) and to improve the quality and multidisciplinary nature of research in nutritional sciences and/or obesity by providing shared access to specialized technical resources and expertise (see http://www.niddk.nih.gov/researchfunding/research-programs/Pages/nutrition-obesity-centers.aspx). The goals and organization of these centers are philosophically aligned with those of the DDRCCs described above. NIDDK Central Repository The NIDDK provides access to reagents, data, DNA and biospecimens through the NIDDK Central Repository (see https://www.niddkrepository.org/home/). The data and samples have been collected for over a decade from many of the large studies that have been sponsored by NIDDK. There is a relatively straightforward application process to obtain access to these resources. In addition, the NIDDK web site has a detailed listing of various studies and resources that are available to the NIDDK
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community (http://www.niddk.nih.gov/research-funding/researchresources/Pages/default.aspx).
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In conclusion, NIDDK is committed to advancing the mission of supporting research in digestive and liver disease, to support public awareness and education and ultimately to improve health. We welcome input and suggestions from the academic community, particularly in developing workshops as new or emerging areas of interest arise.
References
Pasca di Magliano M, Forsmark C, Freedman S, Hebrok M, Pasricha PJ, Saluja A, Stanger BZ, Holt J, Serrano J, James SP, Rustgi AK. Gastroenterology. 2013;144:e1-4
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Andersen DK1, Andren-Sandberg Å, Duell EJ, Goggins M, Korc M, Petersen GM, Smith JP, Whitcomb DC. Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop. Pancreas. 2013;42:1227-37
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Box 1. NIDDK Mission and Core Values The mission of the NIDDK is to conduct and support medical research and research training and to disseminate science-based information on diabetes and other endocrine and metabolic diseases; digestive diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases, to improve people’s health and quality of life. NIDDK will pursue the most compelling research to combat the many debilitating and costly chronic diseases within our mission. We will remain firmly committed to basic, translational, and clinical research; research training and career development; and dissemination of health information to improve the lives of patients, their families, and those at risk for these diseases. NIDDK leadership uses the following overarching principles to guide decision making to fulfill our mission.
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Maintain a Vigorous Investigator-Initiated Research Portfolio: The innovativeness and problem solving of individual investigators are crucial for research progress. Therefore, the NIDDK will maintain funding of investigator-initiated grants at the highest possible level. We will also maximize our investments by supporting cross-cutting science that is broadly applicable to many disease-specific research issues.
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Supporting Pivotal Clinical Studies and Trials: Clinical studies will continue to be an integral component of research on the broad spectrum of diseases for which NIDDK has research responsibility. Because many of these diseases disproportionately affect minority populations, we will continue to seek insights and answers to health disparities. We are also maximizing our investments by expanding the investigative community's access to very valuable research resources accrued in our major clinical trials. We are doing this by funding ancillary studies to these trials and by supporting a central repository for biologic materials from clinical trials.
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Preserve a Stable Pool of Talented New Investigators: The ideas and fresh perspectives of new investigators invigorate the research community. Thus, we will strive to ensure that new investigators can realize their potential for contributing to biomedical research, and that today's generation of young scientists will view research as a viable career. We will foster mentorship of new investigators, and promote special consideration for funding of talented new investigators.
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Foster Exceptional Research Training and Mentoring Opportunities: Maintaining an NIDDK-focused pipeline of outstanding investigators is critically important to our research progress. We will continue to support significant opportunities at the graduatestudent and postdoctoral levels, as well as through research career development awards, and undergraduate research educational opportunities. Ensure Knowledge Dissemination through Outreach and Communication: We are continuing efforts to ensure that the science-based knowledge gained from NIDDKfunded research is imparted to health care providers and the public for the direct benefit of patients and their families.
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Table 1. Program Staff, Division of Digestive Diseases and Nutrition, NIDDK Name
Title
Contact Information
Program Area
Program
Observational and Investigational Clinical Research;
[email protected]
Dana
Director
Biomedical Devices, Surgical Interventions, and Medications
301-594-8879
Program Director
Basic Neurogastroenterology; Gastrointestinal Development, [email protected] Epithelial Biology, Stem Cell Biology, and Inflammation 301-402-0671
Densmore,
Program
Institutional Training; Small Business Technology
Christine
Director
Development
[email protected] 301-402-8714
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Carrington, Jill
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Andersen,
Fatty Liver Disease; Genetic Liver Disease; HIV and Liver; Program Doo, Edward
Cell Injury, Repair, Fibrosis, and Inflammation; Pediatric Liver Director
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Disease; Viral Hepatitis and Infectious Diseases
[email protected] 301-451-4524
Special Projects in Nutrition, Obesity, and Digestive Diseases; Program Evans, Mary
Lifestyle Interventions in Obesity; Nutrition Obesity Research Director
Centers; Diet & Physical Activity Assessment Methodology Clinical
Hall, Sherry trials
[email protected] 301-594-4578
[email protected]
Clinical trials specialist, supporting multi-center clinical trials
specialist
301-435-8150
Program
Frank
Director
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Gastrointestinal and Nutrition AIDS; Gastrointestinal Hamilton,
Endoscopy Research; Gastrointestinal Mucosa and Immunology; Gastrointestinal Motility
Hoofnagle,
Deputy
Jay
Director
James,
Division
Stephen
Director
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Basic and Clinical Research on Liver Diseases
Oversight of DDDN Programs
Director
Kuczmarski,
Program
Robert
Director
Obesity Prevention and Treatment
Maruvada,
Program
Padma
Director
301-594-8877 [email protected] 301-496-1333 [email protected]
301-594-7680
Genetics, Genomics, and Microbiome Studies of the GI Tract, [email protected] Liver, and Pancreatic Diseases, Nutrition, and Obesity 301-451-8875
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Karp, Robert
[email protected]
Nutrient Metabolism; Clinical Obesity and Nutrition
[email protected] 301-451-8354 [email protected] 301-594-8884
Program
Gastrointestinal Host-Microbial Interactions, Basic Mucosal
[email protected]
Director
Immunology and Inflammation
301-451-3759
Perrin, Peter
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Digestive Diseases Research Centers; Digestive Diseases Podskalny,
Program
Judith
Director
and Nutrition Career Development and Fellowships; Loan
[email protected] 301-594-8876
Repayment Program Liver Bioengineering and Biotechnology; Cell and Molecular Program
Biology of the Liver; Developmental Biology and
Director
Regeneration; Drug-induced Liver Disease; Gastrointestinal Neuroendocrinology; Exocrine Pancreas; Pancreatitis
[email protected]
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Serrano, Jose
301-594-8871
Autoimmune Liver Disease; Acute Liver Failure; Bile, Bilirubin Program
and Cholestasis; Complications of Chronic Liver Disease;
[email protected]
Averell
Director
Gallbladder and Biliary Diseases; Liver Cancer; Liver
301-451-6207
SC
Sherker,
Transplantation
Torrance,
Clinical
Rebecca
Trialist
Unalp-Arida,
Program
Epidemiology, Clinical Trials, Digestive Diseases, and
[email protected]
Aynur
Director
Nutrition
301-594-8879
Clinical
Clinical trials specialist, supporting multi-center clinical trials
[email protected]
Trialist
PLEASE ADD A DESCRPITOR
+1 301 594 0056
Van
Raaphorst, Rebekah
Yanovski,
Program
Susan
Director
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Obesity and Eating Disorders
[email protected]
301-594-7024
[email protected] 301-594-8882
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Table 2: NIDDK supports digestive diseases research through many different types of grants* Investigator initiated projects: R01, R03, R15, R18, R21
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Large research programs (P01, R24, U01, U54) Clinical studies and trials (U34, U01) Research Centers (P30, P50)
Small business (R41, R42, R43, R44)
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Conferences, curriculum, others (R13, R25)
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Fellowship, institutional training, and career development (F, T and K grants)
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*Most common grant types: there are others for special purposes that are typically part of special announcements
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Table 3. Translational and Clinical Research Studies Supported by Division of Digestive Diseases and Nutrition, NIDDK Study Name Study website Gastrointestinal Gastroparesis Research http://jhuccs1.us/gpcrc/ Consortium IBD Genetics Consortium http://ibdgc.uchicago.edu/ Intestinal Stem Cell https://iscconsortium.org/ Consortium* Self-Administered CBT for http://ubbmc.buffalo.edu/research/ibsos.php IBS MERIT UC http://merit.web.unc.edu/ PROTECT UC http://www.cscc.unc.edu/protect/ Probiotics to Reduce the Website is not available Incidence of Diarrhea and Enteropathy in Children in Peru (PRIDEC-Peru) Liver Hepatitis B Clinical http://www.hepbnet.org/ Research Network Acute Liver Failure www.utsouthwestern.edu/labs/acute-liver/about/ Pediatric Acute Liver www.palfstudy.org/ Failure Network Childhood Liver Disease www.childrennetwork.org/ Research and Education Network (ChiLDREN) Drug Induced Liver Injury https://dilin.dcri.duke.edu/ Network (DILIN) Nonalcoholic https://jhuccs1.us/nash Steatohepatitis (NASH) Clinical Research Network Obesity Life Moms https://lifemoms.bsc.gwu.edu/web/lifemoms/home?p_p_id =58&p_p_lifecycle=0&_58_redirect=/ Look AHEAD http://www.lookaheadtrial.org/public/home.cfm Teen-LABS http://www.cincinnatichildrens.org/research/divisions/t/teen -labs/default/ *Basic research network that includes research aims involving human subjects
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Table 4. Digestive Disease Research Core Centers and Nutrition and Obesity Research Centers
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See attached Excel spreadsheet
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Figure 1. NIDDK Extramural Research Funding by Category (Competing and Noncompeting). The relative funding levels of NIDDK extramural research categories are shown for fiscal years 2003-2014. The relative funding levels for each category have remained fairly stable since FY2003. These data support the NIDDK core values to maintain a strong investigator-initiated R01 program, preserve a stable pool of talented new investigators, support key clinical studies and trials, and continue strong support of training and career development programs.
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Figure 2: Funding Opportunity Announcements to Support Translational Research for Therapeutic Discovery and Development. This figure illustrates a “translational pipeline” for the development of novel therapeutics. The different stages of therapeutic discovery and development are labeled across the top of the pipeline. The horizontal bars (in blue) are labeled with funding opportunity announcements that are designed to address key research needs/challenges for the indicated stages covered by the width of the bar. For more information on each stage and specific funding opportunity announcements, please visit: http://www.niddk.nih.gov/researchfunding/process/translational-research-therapeutic-discoverydevelopment/Pages/default.aspx.
NIDDK Division of Digestive Diseases and Nutrition Research Centers (P30)
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Institution
Principal Investigator
Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Diseases
Digestive Diseases Research Centers (P30)
Mayo Center for Cell Signaling in Gastroenterology Digestive Health Center: Bench to Bedside Research in Pediatric Digestive Diseases Center for Gastrointestinal Biology and Disease CURE: Digestive Diseases Research Center Silvio O. Conte Digestive Diseases Research Core Centers Center for GI Infection and Inujury USC Research Center for Liver Disease Regulatory Factors in the GI Tract
Mayo Clinic Rochester Cincinnati Childrens Hospital Medical Center U. of North Carolina Chapel Hill U. of California Los Angeles
Jorge Bezerra Robert Sandler Juan Rozengurt Michael Nathanson Hashem El-Serag Neil Kaplowitz Nicholas Davidson
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Yale University Baylor College of Medicine U. of Southern California Washington University
Nicholas LaRusso
Vanderbilt University U. of Pennsylvania Albert Einstein college of Medicine U. of Chicago U. of Michigan
Richard Peek Anil Rustgi
Centr for the Study of Inflammatory Bowel Disease UCSF Liver Core Center Hopkins Digestive Diseases Basic and Translatoinal Research Core Center Integrated Epithelial and Mucosal Biology Cleveland Digestive Diseases Research Core Center
Ramnik Xavier Jacquelyn Maher
Allan Wolkoff
Eugene Chang Chung Owyang
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Massachusetts General Hospital U. of California San Francisco
Molecular and Cellular Basis for Digestive Diseases Center for Digestive and Liver Diseases Liver Pathobiology and Gene Therapy Research Core Center IBD and Mucosal Inflammation, Immunology and Microbiology of the GI Tract Gastrointestinal Hormone Research Core Center
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Johns Hopkins University Children's Hospital Corporation Boston Case Western Reserve University
Obesity Nutrition Research Centers U. of Alabama at Birmingham U. of North Carolina Chapel Hill
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LSU Pennington Biomedical Research Center Massachusetts General Hospital U. of Minnesota
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Washington University Boston Medical Center U. of Colorado Denver U. of Washington Columbia University U. of Michigan U. of Maryland Baltimore
UAB Nutrition Obesity Research Center UNC-CH Nutrition Obesity Research Center Washington University Nutrition Obesity Research Center Boston Nutrition Obesity Research Center Colorado Nutrition Obesity Research Center Nutrition Obesity Research Center New York Nutrition Obesity Research Center Nutrition and Obesity Research Center Mid-Atlantic Nutritoin Obesity Research Center Nutritional Programming: Environmental and molecular Interactions Nutrition Obesity Research Center at Harvard Minnesota Obesity Center
Mark Donowitz Wayne Lencer Fabio Cominelli
David Allison Steven Zeisel
Samuel Klein Susan Fried James O. Hill Michael Schwartz Xavier Pi-Sunyer Charles F. Burant Alan Shuldiner Eric Ravussin Allan Walker Allen Levine
