Section of Endocrinology
300 Cedar St., TAC S141
New Haven, CT 06520-8020
Tel: 203.737.5071
Fax: 203.737.5558
kathleen.catalano@yale.edu
The Yale School of Medicine has a large number of shared-resource core facilities that are available to support the research activities of DERC members. These core resources serve to amplify the overall research productivity of the DERC and have allowed us to focus the direction of the DERC scientific cores toward those services not readily available to our membership.
The Yale General Clinical Research Center (GCRC), founded in 1960, has a long history of scientific accomplishments relevant to the DERC including: 1) defining the pathophysiology of type 2 diabetes (Shulman); 2) developing "insulin pump" therapy for type 1 diabetes (Sherwin & Tamborlane); 3) identifying multiple genes that contribute to hypertension (Lifton); 4) deciphering the mechanism of malignancy-associated hypercalcemia (Broadus); and 5) exploring the metabolic consequences of childhood obesity (Caprio). In 2000, Yale invested more than $1 million to update the space occupied by the GCRC. It is currently a 14-bed unit with facilities for intensive metabolic studies, and a metabolic kitchen. In 2003, the Children's GCRC merged with the Adult GCRC under Dr. Sherwin's direction, resulting in a remarkable streamlining of the daily operation of the unit which led to an increase in diabetes-related research. In 2004 a site visit team gave the Yale GCRC a score in the outstanding range. At that time, Dean Robert J. Alpern convened a Strategic Planning Committee to evaluate the status of clinical and translational research at Yale School of Medicine. The strategic planning committee recommended that Yale University create a new center, the Yale Center for Clinical Investigation (YCCI) that would significantly expand the functions of the existing GCRC.
The YCCI was established in the fall of 2005 incorporating the GCRC within its structure. YCCI was virtually identical in its vision, design, and scope with that later proposed in the RFA for CTSA applications. Steps were taken prior to the CTSA submission to establish some components of YCCI, including renovation of a new outpatient facility. The funding of the CTSA at Yale in October, 2006 (P.I. R. Sherwin) has greatly accelerated the development of YCCI, and in the process will undoubtedly strengthen clinical and translational research as well as training in diabetes as well as provide new cost savings opportunities for the DERC to partner with YCCI.
The Operations Center will house all YCCI personnel who are needed to assist investigators in the development, implementation and oversight of clinical and translational research studies.
The new Operations Center provides the infrastructure to support YCCI's as well as the DERC's mission to effectively support clinical and translational investigators at Yale in the development, implementation and oversight of their studies. All of the resources that are needed for every aspect of cutting-edge studies will be available at one site. The Operations Center will provide a critical point of contact for industry and the staff in the Operations Center will work to identify new research opportunities that are matched to appropriate investigators. Dr. William V. Tamborlane serves as the Director of the Operations Center. In this role he is ideally placed to facilitate the development and successful implementation of the new DERC Diabetes Translational Core.
The need for YCCI to develop a new outpatient facility for the performance of minimal and low risk outpatient studies was given a high priority, and as a result, it will become fully operational in November, 2006. This facility includes:
The importance of the new Outpatient Center extends beyond simple enhancement of space for clinical studies. Having a central location for outpatient studies will facilitate cost-effective utilization of research staff (e.g., nurse coordinators) that may be engaged in studies with more than one investigator, as well as oversight of ongoing studies. Use of YCCI research staff will free investigators of many of the burdens of administrating the day-to-day management and enhance the quality of supervision and oversight of research staff. Integration of activities of the YCCI Outpatient Clinical and Translational Research Center and the Operations Center will be facilitated by locating both important components of our program in the same location. It should also be noted that the site at 2 Church Street South was selected because it is in close proximity to the academic offices of research faculty in the Yale School of Nursing and EPH, as well as the School of Medicine. The outpatient center will also serve as a training and certification site for new study coordinators and research assistants.
This resource originally served as the core laboratory of the GCRC. Because a major strength of the GCRC was in patient-based diabetes-related research, the primary orientation of this laboratory has been substrate, hormone and cytokine analyses, and thus directly relevant to DERC research programs. As a result, this facility's technical staff and equipment are an important resource for human-based diabetes research and offer a valuable cost savings to the DERC. The DERC Physiology Core is therefore able to exclusively focus its limited resources on the measurement of hormones from rats and mice experiments. The laboratories consist of a 125 sq. ft blood processing laboratory, a 250 sq. ft laboratory for substrate measurements and a 750 sq. ft laboratory equipped for immunoassays, HLPC /ELISA analyses and tissue culture. Recently, the resources of the YCCI Analytical Core have been enhanced by CTSA funding including: new equipment (Luminex) and creation of a freezer farm for sample/DNA storage.
Designed to optimize effective use of modern research technologies by clustering them around common themes. There are 6 such clusters: (1) imaging (cellular and human-based research); (2) clinical laboratory methods; (3) physiological and metabolic procedures; (4) cognitive and behavioral methods; (5) methods for drug and device development; and (6) methods for the production of cells and vectors. YCCI developed this type of clustering to overcome the problem often encountered by new investigators, namely the difficulty of having to seek out a patchwork of informal input from a variety of centers and core laboratories. YCCI will now provide an integrated mechanism for this purpose. Within YCCI, a sub-committee devoted to Yale-wide optimal integration of core resources will be established, composed of the directors of core laboratories and representatives from their user groups. This committee will serve as a referral resource, connecting investigators with the appropriate cores and triggering an informal iterative process to help each investigator choose the most appropriate methodologies for his/her project. In parallel, YCCI is in the process of constructing a website to provide on-line descriptions of all cores.
This center was established in 1985 to develop novel magnetic resonance methods for studies in health and disease. A unique component of the MRRC research program is 13C MRS metabolic imaging to follow the metabolism of substrates in brain, liver, and muscle. Yale has also played a pioneering role in development of functional magnetic resonance imaging (fMRI). Over 30 NIH funded investigators from 11 Yale departments make extensive use of the MRRC facilities, about half of whom are DERC members conducting diabetes-related research. The MRRC occupies 27,000 square feet of the new TAC building and has a 30 person research staff with extensive experience in the development of MR technology. Major equipment includes a 4T Bruker whole body system for human MRS, a 3T Siemans Trio for fMRI, a 1.5T Siemans Sonata for MRI, fMRI, and MRS, 11.7T, 9.4T and 4.7T horizontal small animal systems, a 500 and 600 MHz vertical MRS system for protein structure and biochemical analysis. These systems have state-of-the-art electronics and are capable of performing the full range of MRS and MRI sequences, including 13C, 31P, and 1H MRS, spectral editing, short echo acquisition, and 3/4D spectroscopic imaging. A 7 Tesla magnet has recently been purchased and will shortly be available for human research in diabetes.
The MRRC is fully equipped for patient studies, including a waiting area, interview room, changing rooms, showers, and two fully equipped patient research beds. There has been a steady increase patient-based research protocols using either fMRI or MRS and a rapidly growing list of investigators who incorporate MRI or MRS into their protocols. Funding of the CTSA provides DERC investigators with the opportunity to obtain assistance in designing protocols and performing MRI/MRS studies as well as providing pilot support for initiatives in diabetes.
The PET center was built in 2005 to advance molecular imaging research at the University. The Center occupies ca. 20,000nsf of newly constructed space and has two scanners: a CTI HR+ and a HRRT scanner, along with space for a dedicated animal PET scanner. It has a state-of-the-art radiochemistry facility that will permit the development and use of a complete line of PET radiopharmaceuticals labeled with the most common PET isotopes: 11C, 15O, 13N, and 18F. The Center also has a PET physics and data analysis group to provide training and consultation to DERC investigators.
This laboratory, which was founded in 1980, serves as a critical core, providing a wide range of state-of-the-art genomic and proteomic biotechnologies to hundreds of investigators throughout the Yale campus. With 45 full-time staff members, more than 25,000nsf of space, and 75 major instrument systems purchased at a cost of $11 million dollars, the Keck Laboratory is one of the largest academic biotechnology resource laboratories of its kind in the world. It offers a wide range of genomic and proteomic syntheses and analyses that include DNA microarray and Affymetrix gene chip technology, oligo and peptide synthesis, DNA and protein sequencing, biophysical analysis of proteins and other biopolymers (including size exclusion HPLC/laser light scattering and stopped flow fluorescence/absorbance), mass spectrometry (MS), and biostatistical analyses of data. The rapid growth of the DNA Microarray Resource has been aided by support received from of a NIDDK Microarray Biotechnology Center Grant, which is one of 16 centers nationally. The Keck Laboratory also provides a single nucleotide polymorphism (SNP) genotyping service with a maximum throughput of >20,000,000 SNP genotypes/day, based on MS analysis of the products of single base extension reactions. In addition, the Keck lab offers a variety of protein profiling technologies and is closely associated with the Yale/NHLBI Proteomics Center, one of 10 national centers.
The Keck Resource Laboratory also offers the following services: 1) amino acid analysis/sequencing; 2) large scale peptide synthesis; 3) HPLC SEC/laser light scattering determination of native protein molecular weights; 4) mass spectroscopy; 5) oligonucleotide syntheses; 6) protein sequencing; 7) small scale peptide synthesis. Since its founding, the Keck facility has been self-supporting with respect to recovering its operating expenses from user fees.
Led by Hongyu Zhao, Ph.D. (Professor of Epidemiology & Public Health), this center assists in the statistical analysis of genomics data, including microarray gene expression data and SNP data. Assistance is provided at three levels: primary analysis, advanced analysis, and experimental design. Dr. Zhao's group has also developed novel statistical methods to map diabetes- and obesity-related genes. Their current focus is on the efficient use of SNPs in both pedigree-based and population-based studies, and the understanding and use of haplotypes in genetic studies. This program is enhanced by collaborations with Computer Science faculty and by the presence of the Center for High Performance Computation (HPC) equipped with a state-of-the-art,128 node Beowulf cluster “supercomputer”.
This YCCI-based core provides the infrastructure and services needed to conduct translational research. The DERC's members benefit from this structure in a number of ways: 1) guidance on the efficient design and analysis of clinical research proposals, including the preparation of grant proposals and questionaires; 2) provision of consultative services regarding the design and analysis of research projects; 3) providing education and training for faculty, students and fellows; 4) development of new approaches and methods for the design and analysis of clinical research studies. The goal of the Biostatistics and Study Design Core is to enhance the design and analytical infrastructure particularly in the following areas: (1) genomics and proteomics; (2) genetics and genetic epidemiology; (3) design and analysis of clinical studies including randomized trials; (4) spatial analysis; (5) clinical epidemiology and (6) cost effectiveness and cost benefit analysis.
The YCMI serves as a focus for training and systems development for a range of research projects. YCMI occupies 8,000 sq ft in the same building as the Keck Lab. It is headed by Perry Miller, M.D.,Ph.D., and has 15 core faculty members. It offers DERC investigators access to a novel data base management system, Trial/DB, a powerful, flexible, web-accessible database designed to support clinical trials and clinical research in a variety of areas, including diabetes.
The School of Medicine through its Division of Animal Care has a centralized, AAALAC accredited resource that provides a full range of clinical veterinary services on a 24-h basis as well as housing and husbandry services for animal research conducted by DERC investigators.
Flow Cytometry/Cell Sorting Core. This core maintains two instruments; a Becton Dickinson dual laser FACS IV and a BDFACS analyzer as well as interfacing computers and technical support. The current configuration of the Yale Cancer Center FACS IV allows simultaneous measurement of four different parameters on each individual cell. The addition of electrostatic sorting to flow cytometry systems allows separation as well as analysis of individual cells at rates exceeding 1000 cells/second. Users are charged an hourly rate.
Mass Spectroscopy Core. This core houses a VG ZAB-SE double focusing high mass range spectrometer (purchased with DRR-BRS Shared Instrument Grant plus Cancer Center funds) with a continuous flow FAB probe and a 35KV cesium ion gun as well as a triple quadrupole mass spectrometer equipped with an electrospray ion source, a liquid chromatograph and three gas chromatographs. It is used for confirmation of the structure of proteins cloned from oligonucleotide probes, molecular structure analyses, to identify peptides produced from enzymatic digests, identify post-translational modifications of proteins, etc. Charges are based on an hourly rate.
vTissue Retrieval Core. Operated by the Department of Pathology to facilitate the acquisition of human tissues to investigators as well as to provide diagnostic services. Supply and technical costs are subsidized.
Transgenic Mouse Core. The Cancer Center operates a transgenic and knockout mouse facility that shares expertise with the DERC Transgenic facility directed by Dr. Flavell.
Numerous other shared facilities exist to support faculty research such: Cesium-137 irradiation for cell cultures and small animals; special laboratories and hood facilities for iodination of proteins and peptides; and graphics workstations that offer molecular modeling including the capability of performing resolution and manipulation of molecular structures in three dimension. Most of the instruments listed above were purchased with funds made available by shared instrumentation awards from NIH.
This NIDDK funded center is under the direction of Dr. Gerald Shulman, the Associate Director of the DERC. This Center serves to complement DERC resources by providing the resources to study, from a metabolic perspective, novel transgenic and knockout mice. It includes the following cores: Animal Care, In Vivo Metabolism, In Vitro Metabolism, Analytic, and MRS/MRI Cores. The goal is to offer a resource to perform metabolic phenotyping of diabetic and insulin resistant mice in collaboration with investigators around the world. The facility is housed in the TAC building one floor above the DERC offices.
Under the direction of Dr. Sherwin, this center brings together 16 clinical investigators in such areas as insulin delivery systems, clinical physiology, glucose sensor technology, behavioral research and imaging technology. There are two major components to Center activities, namely a clinical trial involving children with diabetes and a basic science component that utilizes novel technologies to study brain function and metabolism and how they are affected by hypoglycemia. The clinical trial, led by Dr. Tamborlane tests whether the introduction of glucose sensor technology can be used in the clinical setting to reduce the risk of severe hypoglycemia in children receiving intensive insulin therapy. These studies led the NIH to initiate Direct Net, which has provided critical information on the utility and the limitations of glucose sensor technology. The long-term goal of the project is to develop a closed loop artificial pancreas, which would be an enormous benefit for patients with diabetes. The basic science component tests from multiple perspectives (microdialysis, MR Spectroscopy, and fMRI) the hypothesis that a key role of brain glucose metabolism is to provide the energy needed to maintain glutamate-glutamine cycling and neurotransmission and that hypoglycemia prevents these processes, and this in turn diminishes regional brain activation in response to a cognitive task. On the other hand, diabetic patients with a history frequent hypoglycemia and reduced recognition of hypoglycemia have developed metabolic brain adaptations which allow them more effectively use alternative fuels for the brain's basic energy needs, in particular short and medium chain fatty acids. The long-term goals of the Center are to develop a mechanical (artificial) pancreas to prevent hypoglycemia, to discover drugs that could reverse defects in hypoglycemia defense systems in diabetes, or to identify alternative fuels that could be effectively used by the brain to protect it from injury. All the participants are DERC members.
Established in 2001 by the Nursing School, this center focuses on the development, understanding, and testing of interventions to enhance self and family management of chronic conditions, including diabetes. It is one of nine Core Research Centers in the country funded by the National Institute of Nursing Research promote interdisciplinary collaborations through use of shared resources, collective data and application management systems, and community-based participation in development and dissemination of the work. The Center mentors young scholars and trains investigators to conduct research in self and family management, directed at vulnerable populations.
The POA has ~40 research projects funded by the NIA-sponsored Claude D. Pepper Center and by investigator-initiated NIH and foundation grants. The common thread of the research conducted at the POA is the development and testing of effective strategies for enhancing function and quality of life of older persons experiencing multiple impairments and chronic diseases, including diabetes through epidemiological studies, intervention trials and outcome studies. A major focus is the application of lessons learned from clinical trials to community health. The POA, DERC and YCCI plan to partner in the funding of pilot projects and symposia to foster collaborations and more effective program integration.
This program provides expertise in evaluating and improving quality of care, determining cost-effective strategies, tracking trends in patterns of care, developing and evaluating disease management and decision support tools, profiling hospital performance, and evaluating the effectiveness of health care strategies. The focus is on improving health care (e.g. cardiovascular disease in diabetes) by examining the balance of safety, effectiveness, and costs of health care delivery. A key goal of the program is to analyze large, complex observational data and translate findings to improve the quality of health care to guide decisions about the allocation of health care resources. The Core, led by Harlan Krumholz (a DERC member), consists of clinical investigators, statisticians, computer scientists, economists, epidemiologists, management experts, and administrative staff. They create and manage large national databases as well as coordinate research efforts with collaborative partners, including CMS, the Department of Defense, NHLBI, the Agency for Healthcare Research and Quality (AHRQ), and the CDC.
This center is an interdisciplinary program that aims to improve the world's diet, prevent obesity, and reduce weight stigma by establishing creative connections between science and public policy, developing targeted research, encouraging frank dialogue among key constituents. A key objective is to work with, through, and when needed, against the key institutions that affect national and global nutrition. These include governments, food and agriculture industries, the media, the scientific community, and communities. The Rudd Center's membership includes diverse faculty from the College, EPH, Law, Nursing, and the Medical School. An example of a DERC program that interfaces with the Rudd Center is the school-based clinical research in obesity conducted by the team headed by Drs. Margaret Grey and Sonia Caprio, both DERC members.
©
Yale School of Medicine
Last updated
10/15/08
Privacy policy Site editor
