The overall objective of the Yale Diabetes Research Center (DRC) is to promote novel and cutting edge research in diabetes and related metabolic disorders by facilitating the interactions of basic and clinical scientists, and in turn the development of interdisciplinary, interdepartmental scientific initiatives that may be translated from the bench to the bedside and ultimately into new strategies for the prevention, treatment and cure of patients with or who are at risk for diabetes. The design of the DRC is aimed at developing the appropriate infrastructure within our institution that would: a) serve as a catalyst to enhance existing programs in diabetes-related research; b) encourage established investigators not presently working in diabetes-related areas, to bring their expertise to bear on problems relevant to diabetes in the broad sense; c) efficiently organize time-consuming and/or costly techniques through Core facilities to leverage funding and enhance the productivity of investigators conducting diabetes research; d) promote the training and development of young clinicians and scientists engaged in diabetes related research; and e) create a stimulating environment that promotes the interchange of information and ideas among scientists at the local and national level.
In 1993, Yale University received funding from NIDDK to establish a DRC. Because of the need to phase-out a center that was closing, initial support was limited. Nevertheless, most of the projected Core resources were immediately operational, the Pilot and Feasibility (P&F) Program was fully funded, the administrative structure and Enrichment Program were developed. The Program Directors, the Executive Committee and Core Directors have for the most part remained in place since the start of the grant, thereby allowing us to gain valuable experience in how to best promote diabetes research locally and to be responsive to the needs of members. In the process, we have restructured and consolidated some Cores, expanded the operation of others and established new Cores. At the outset, to encourage use of the Cores, we decided to minimize "payback" charges for Core services since funding of individual grants antedated the DRC. However, we soon instituted fees to minimize frivolous use of Core Resources and extend the limited funds available to the DRC. A major effort was made to increase the visibility of the DRC within the University through a "high profile" Enrichment Program (in part supported by private and University funds), including DRC sponsored diabetes symposia, an annual retreat and visiting lectureships in diabetes-related research, including some in basic science departments to stimulate their interest in diabetes. The Executive Committee decided from the outset to invest much its resources in the P&F Program, believing it was the most productive way of making a rapid impact on diabetes research locally. Overall, the P&F program more than fulfilled this mission. In most cases P&F applications were the stepping-stone for peer-reviewed grant support and were judged by extramural reviewers Excellent or Outstanding, reflecting the high quality of the research proposed. Finally, the training environment at Yale was substantially enhanced by the creation in 2001 of the Investigative Medicine Program, a unique PhD program exclusively for physicians in clinical departments. Two of the first 4 doctoral candidates enrolled worked with DRC members on diabetes projects and both remain in diabetes research. The success of our efforts in the DRC's first decade is best demonstrated by a 3-4-fold increase in DRC-related funding by members from 1992 to 2002, reaching $45 million per year.
The DRC is directed by clinical investigators actively engaged in diabetes and/or endocrine research. Gerald I. Shulman, MD, PhD and Kevan Herold, MD servce as co-Program Directors. They are advised by an Executive Committee composed of faculty from basic and clinical departments in the School of Medicine. An External Advisory Board oversees the performance of the DRC and provides counsel to the Program Directors as well as Dean Nancy Brown, MD. The DRC consists of an Administrative Core and six Scientific Cores (Clinical Metabolism, Molecular, Transgenic Mice, Physiology, Cell Biology, and Diabetes Translation). The Administrative Core's functions include: program management; promotion of research in diabetes; and provision of support for the P&F and Enrichment programs. The Clinical Metabolism Core (directed by Dr. Shulman) offers access to state-of-the-art metabolic substrate analyses. The Molecular Genetics Core consists of two sub-cores: Molecular (directed by Dr. Philbrick) offers expertise for the generation of constructs to create transgenic and knockout mice and training in molecular techniques. The Gene Targeting sub-core (directed by Dr. Flavell) has unique resources to create novel transgenic and knockout mice models and maintains colonies of NOD and humanized mice for diabetes research. The Physiology Core (directed by Dr. Herzog) assists in measurements of rodent in vivo metabolism and hormone secretion. The Cell Biology Core (directed by Dr. Bogan) offers a state-of-the-art imaging facility and expertise in in vivo cell imaging, confocal microscopy, and electron microscopy. The newer Clinical Translational Core (directed by Dr. Tamborlane) provides an infrastructure to facilitate patient-based diabetes research, a major historical and current scientific strength of Yale DRC membership.
The guiding principle in the design of the DRC has been to avoid duplicating existing Core resources available to faculty, such as protein sequencing, oligonucleotide, DNA analysis, microarray, flow cytometry, tissue retrieval cores, as well as the CTSA supported analytical laboratory for hormone and cytokine analyses in humans. DRC members are generally charged a service fee for most core services amounting to the total supply costs, and in some cases for personnel costs. To maximize our ability to provide a wide range of services to DRC members we have expanded existing limited-access laboratory facilities as much as possible. This allows us to minimize costs by taking advantage of existing personnel and equipment. For example, we have utilized the existing Cellular Imaging Core supported by the University in the design of the Cell Biology Core. The Clinical Metabolism and Physiology Cores benefit from the instrumentation provided by the Yale NMR Center, the Mouse Metabolic Phenotyping Center (which provides resources for mice studies only) and the YCCI Analytical Core Laboratory. The Molecular sub-core takes advantage of the extensive resources of the Keck Center and the Gene Targeting sub-core expands the fully operational facility supervised by Dr. Flavell. Finally, the Diabetes Translational Core leverages the infusion of new resources provided by a NCATS CTSA to establish the Yale Center for Clinical Investigation (YCCI) directed by Drs. Brian Smith and John Krystal.