Diabetes, either through autoimmune destruction of islets in type 1 diabetes or cellular resistance to insulin in type 2 diabetes, leads to hyperglycemia and other metabolic defects. Over time, these metabolic abnormalities cause cell and tissue injury and eventually diseases such as heart attacks, stroke, renal failure, peripheral and autonomic neuropathy, and blindness. An important, but elusive, goal for diabetes research has been therapeutics that would prevent or reverse the cellular injury induced by hyperglycemia. A major obstacle is the limitation of animal models to mimic the complexity and chronicity of the human disease.
Significant advances have taken place in approaches to obtain, store, and study human tissue. A goal of this workshop is to learn from the successes in other diseases and better translate them to diabetes research. Of particular importance to diabetes complications research is the availability of clinical data to inform the human tissue findings. The foundation for any consideration of obtaining human tissue is the scientific need and questions that could be addressed.
- Review the current use of human post-mortem tissue for research in diabetes complications and other relevant diseases.
- Review the current knowledge on the human pathology of the development of complications from type 1 and type 2 diabetes.
- Review current approaches to the study of human post-mortem tissue. Although tissue quality, collection techniques, and preservation are important, they will not be part of the focus of the meeting.
- Identify specific research questions that could be addressed with human tissue obtained after death from individuals who have pre-consented to donating tissue and who have medical records that fully characterize their diabetes.
- Develop ideas that could be used for future initiatives from NIH and JDRF.
Workshop Organizing Committee
Matthew D. Breyer, MD, Lilly Research Laboratories
Michael Brownlee, MD, Albert Einstein College of Medicine
Alvin Powers, MD, Vanderbilt University
Kristin M. Abraham, PhD, NIDDK
Michael F. Flessner, MD, PhD, NIDDK
Teresa L. Z. Jones, MD, NIDDK
Christian J. Ketchum, PhD, NIDDK
December 12, 2011
- 3:00 p.m.
- Opening Remarks
Gregory Germino, M.D. Deputy Director, NIDDK
Helen Nickerson, Ph.D., JDRF
- 3:15 p.m.
- Keynote Address - Impact of Human Tissue on Diabetes Complications Research
Michael Brownlee, M.D., Albert Einstein College of Medicine
Advances in Understanding Disease Pathogenesis Using Human Post-mortem Tissue
- 3:45 p.m.
- Multiple Sclerosis
Bruce D. Trapp, Ph.D., Cleveland Clinic
- 4:15 p.m.
- Atherosclerotic Plaques
Renu Vermani, M.D., CVPath Institute
- 4:45 p.m.
Joel E. Kleinman, M.D., Ph.D., National Institute of Mental Health
- 5:15 p.m.
Jan H. N. Lindeman, M.D., Ph.D., Leiden University
- 5:45 p.m.
- 6:15 p.m.
Vahram Haroutunian, Ph.D., Mount Sinai School of Medicine
- 6:45 p.m.
- Mitochondria and Neurodegenerative Disease
Douglas C. Wallace, Ph.D., University of Pennsylvania
- 7:15 p.m.
- GTEx Program
Jeff Struewing, M.D., M.S., National Human Genome Research Institute
- 7:45 p.m.
- Adjournment for dinner
December 13, 2011
Diabetes Research Using Human Post-mortem Tissue
- 8:30 a.m.
- Joslin Medalist Program
George King, M.D., Joslin Diabetes Center
- 9:00 a.m.
- JDRF Network for Pancreatic Organ Donors With Diabetes (nPOD)
Mark A. Atkinson, Ph.D., University of Florida
- 9:30 a.m.
- Renal System Biology
Matthias Kretzler, M.D., University of Michigan
- 10:00 a.m.
Innovative Approaches to the Study of Human Post-mortem Tissue
- 10:15 a.m.
- MALDI Imaging Mass Spectrometry
Richard M. Caprioli, Ph.D., Vanderbilt University
- 10:45 a.m.
- Vascular Tissue Microarrays
Marc K. Halushka, M.D., The Johns Hopkins University
- 11:15 a.m.
- Integration of Clinical Data with Biochemical and Genetics Research
Joshua C. Denny M.D., Vanderbilt University
- 11:45 a.m.
Breakout Sessions for Specific Diabetic Complications
Discussion of specific research questions that could be addressed by preconsented post-mortem tissue. The focus should be on the science rather than logistical, procurement, or tissue quality issues. Questions include:
- What is the knowledge base of human pathology studies on the development of complications? Are their gaps in our knowledge?
- What are the similarities and differences between preclinical models and human pathology?
- How do we integrate genomic and epigenomic data?
- How well do the stages of the disease correlate with different pathophysiologic mechanisms?
- What are the best situations for bi-directional investigations between pre-clinical models and human tissue?
- Using human tissue, how can we elucidate factors that retard or advance the development of complications?
- 12:45 p.m.
- Breakout Sessions
- Cardiovascular Disease - Jean Schaffer, M.D. Washington University and Renu Virmani, M.D., CVPath Institute (invited) (Co-chairs)
- Islet Damage - Mark Atkinson, Ph.D., University of Florida, and Alvin Powers, M.D. Vanderbilt University (Co-chairs)
- Nephropathy - Charles Alpers, M.D., Washington University, and Matthew Breyer, M.D., Eli Lilly and Company (Co-chairs)
- Neuropathy - Nigel Calcutt, Ph.D., University of California, San Diego, and Eva Feldman, M.D., Ph.D., University of Michigan (Co-chairs)
- Retinopathy - Timothy Kern, Ph.D., Case Western Reserve University, and Hendrik P. N. Scholl, M.D. Johns Hopkins University (Co-Chairs)
- Tom F Lue, M.D., University of California San Francisco and Aruna V. Sarma, Ph.D. M.H.A, University of Michigan (Co-chairs) (Invited)
- 3:00 p.m.
- Final Discussion
- 4:00 p.m.