Alan Chait, MD


  • Edwin L. Bierman Professor of Medicine
  • Division of Metabolism, Endocrinology and Nutrition

Complete list of published work.

Dr. Chait received his MBChB (MD equivalent) and his MD (PhD equivalent) from the University of Cape Town, South Africa. After completing an internship at Groote Schuur Hospital in Cape Town, he finished his residency and a research fellowship at the Hammersmith Hospital, Royal Postgraduate Medical School, in London, UK. He next became a lecturer in Endocrinology at the London Hospital. He came to the UW as a senior research fellow in Metabolism and Endocrinology in 1975, and was appointed to the faculty in 1977. In 1985 he was appointed Professor of Medicine, and became Head of the Division on Metabolism, Endocrinology and Nutrition in 1996. In addition to clinical teaching and patient care responsibilities at the University of Washington Medical Center, since 1977 Dr. Chait has been funded by the NIH and other sources to study mechanisms of atherogenesis, with a particular focus on the role of diabetes in the pathogenesis of macrovascular disease. He has served as Director of the UW’s Clinical Nutrition Research Unit (CNRU) – recently renamed Nutrition Obesity Research Center (NORC) from 1992 till 2012, and until recently has been a PI for a Program Project to study macrovascular disease in diabetes. He also is the PI on a NIH T32 Training Grant from the NHLBI. He is a member of the American Society for Clinical Investigation and the Association of American Physicians, and serves on several editorial boards.

Research Interests

Dr. Chait’s research focuses on lipoprotein-proteoglycan interactions in atherogenesis; the role of diabetes in the pathogenesis of macrovascular disease; and the links amongst obesity, inflammation, insulin resistance and atherosclerosis.

Obesity, inflammation, insulin resistance and atherosclerosis
Inflammation of visceral adipose tissue is associated with insulin resistance, systemic inflammation and atherosclerosis.  Adipose tissue inflammation is characterized by macrophage accumulation.  Our lab is using in vitro approaches to understand mechanisms by which adipocytes become activated to produce chemotactic factors that recruit macrophages.  We are particularly interested in the role of excess nutrients derived from glucose or various fatty acids, and of dietary cholesterol.  We also use mouse models to study how obesity and nutrient excess leads to adipose tissue and systemic inflammation, and how this inflammation in turn can accelerate atherogenesis.  As part of this work, we are studying how inflammation affects HDL composition and function.

Lipoprotein-proteoglycan interactions in atherogenesis
The interaction of atherogenic lipoproteins with vascular proteoglycans is a critical step in the initiation of atherogenesis.  Lipoproteins that are retained by these matrix molecules can undergo various modifications that make then potentially more atherogenic.  The Chait lab is studying molecular determinants that alter the interaction of lipoproteins with proteoglycans.  These include factors that modify proteoglycan structure so as to alter their ability to interact with lipoproteins, and apolipoprotein determinants of proteoglycan binding.  As part of these studies the Chait lab has discovered that serum amyloid A (SAA), an inflammatory protein that is transported mainly on HDL, can bind vascular proteoglycans and lead to retention of SAA-containing lipoproteins in the artery wall.  Studies are being performed to determine whether SAA plays a direct role in mediating atherosclerosis, or is simply a marker of the inflammation that is part of the atherogenic process.

Diabetes in the pathogenesis of macrovascular disease
Diabetes is a major risk factor for the pathogenesis of premature vascular disease.  Our lab is studying potential mechanisms by which diabetes may cause inflammation and stimulate the interaction of lipoproteins with vascular proteoglycans.  In particular, we are interested in the role of SAA in the pathogenesis of diabetic vascular disease.  For these studies we are using mouse models of both type 2 and type 1 diabetes, and will be studying the effect of SAA deficiency, and overexpression of various inducible SAA isoforms by macrophages in the artery wall.  These studies should provide important insights into the link between inflammation and lipoprotein-vascular wall interactions in the pathogenesis of atherosclerosis in diabetes.