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A Harvard Medical School Affiliate
Welcome to the Joslin Research Website
Joslin Investigator:
Dr. Mark E. Williams
Investigator Specifics:
Professional Details:
Publications
CV not available
Member of Section:
Clinical Research Section
Past Fellows, etc.:
Younes Kitane
Investigators
Adjunct Investigators
Fellows & Team Members
DERC Cores
Research Sections
Joslin Resources
Mark E Williams, MD
Investigator
Joslin Diabetes Center
12/1/1987 -
Dr. Williams' research focuses on clinical studies of the investigational drug Pimagedine. This drug may be capable of protecting remaining kidney function in patients who have diabetes and kidney disease, and may also be helpful in treating patients with end-stage renal disease on hemodialysis.
High blood sugars from diabetes can cause irreversible complications through a variety of biochemical mechanisms. Increasing attention is being given to the excessive interaction of glucose with proteins, leading to the formation of substances called advanced glycated end-products, or AGEs. People with diabetes who have chronically elevated blood glucose levels tend to form excessive amounts of AGEs in various parts of the body. These AGEs accumulate, resulting in cross-linking between involved proteins.
Increased AGE formation has been observed in a variety of animal tissues, including the glomerular basement membranes of the kidney and the coronary arteries. People with diabetes have been shown to have higher levels of AGEs in their blood than non-diabetics, and these levels rise in patients with diabetic kidney disease as the kidney disease worsens. Researchers hypothesize that AGEs also may play an important role in the development of coronary artery disease and peripheral vascular disease in people with diabetes.
Pimagedine appears to prevent AGE formation and AGE-induced protein cross-linking. Pimagedine's ability to prevent complications in diabetes has been demonstrated in animals. It has been shown to reduce diabetic kidney damage, to lessen proteinuria, to prevent the development of diabetic eye disease and improve nerve conduction abnormalities in animals. Dr. Williams is participating in several national clinical trials to see if Pimagedine can have similar effects in humans. It is also being used to see if it can reduce AGE formation in patients already on dialysis and to see if use of the drug is cost-effective and improves the quality Ñ not just the quantity - of life of patients on dialysis.
Selected References:
Williams, M.E., Management of the Diabetic Transplant Recipient, Kidney Int., 1995, 48: 1660-1674.
Williams, M.E., Dam(AGE) in Diabetic ESRD: Role of Advanced Glycosylation; Seminars in Dialysis, 1996, 9 (1): 1-4.
Biographical Sketch:
Dr. Williams is Assistant Professor of Medicine at Harvard Medical School and Senior Physician in the Section on Nephrology at Joslin. He received his medical degree from Indiana University School of Medicine and completed his residency training at Los Angeles County, University of Southern California Medical Center and Boston City Hospital, as well as completing a fellowship in nephrology at Beth Israel Hospital in Boston. Dr. Williams serves on numerous committees related to his areas of research interest and is a Fellow of the American College of Physicians. He is immediate past chairman of the National Kidney Foundation of Massachusetts and Rhode Island, and is chairman of the Council on Diabetic Kidney Disease of the national NKF.
