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Research Summary
I am interested in the molecular and cellular regulation hypertriglyceridemia, particularly in patients and animal models of insulin resistance and diabetes.
Research Activities
Dr. Ginsberg conducts research related to the regulation of the levels and metabolism of apolipoprotein B-containing lipoproteins, the lipoproteins carrying triglycerides and the bulk of cholesterol in blood. These include the atherogenic very low density and low density lipoproteins. Dr. Ginsberg has a particular emphasis on the pathophysiology of hypertriglyceridemia and the dyslipidemia associated with insulin resistance and diabetes mellitus. Research is conducted at three levels: tissue culture using both human and rat hepatoma cells, transgenic mice, and human clinical studies. In cultured cells, Dr. Ginsberg and his associates have described the role of lipid substrate availability in determining if newly synthesized a of degradation and lipoprotein assembly of apoB. His group has characterized the role of the proteasome in the degradation of apoB.
In transgenic mice, he had developed a model of insulin resistance and dylipidemia with many characteristics of the human disorder. This model, as well as others now in use in the lab, allow the group to dissect the important components of substrate availability and genetic control that lead to hypertriglyceridemia. Dr. Ginsberg’s group makes and studies transgenic mice, conducting whole body, cellular, and molecular experiments.
In clinical studies, Dr. Ginsberg is investigating postprandial hyperlipidemia as a risk factor in patients with diabetes. He is also part of a group at Columbia that will be studying the role of glycemic, lipid and blood pressure control in the prevention of cardiovascular disease in patients with diabetes. The latter, named the ACCORD trial, is a 10-year trial with 10,000 patients at 6 sites across the United States. Dr. Ginsberg also has a long record of research into the effects of diet on lipid and lipoprotein metabolism in humans, and has conducted numerous controlled feeding studies in humans.
Positions & Appointments
| 1996-present |
Irving Professor of Medicine |
Columbia University, College of Physicians & Surgeons |
New York, NY |
| 1992-present |
Attending Physician in Medicine |
Columbia University Medical Center |
New York, NY |
| 1995-present |
Program Director, General Clinical Research Center |
Columbia University, College of Physicians & Surgeons |
New York, NY |
| 1995-present |
Director, Irving Center for Clinical Research |
Columbia University, College of Physicians & Surgeons |
New York, NY |
| 1992-present |
Head, Division of Preventive Medicine and Nutrition |
Columbia University, College of Physicians & Surgeons |
New York, NY |
Honors and Awards
Alpha Omega Alpha
1981-1986 Public Health Service Research Career Development Award
1981-1986 Irma T. Hirschl Career Scientist Award
1984 Irvine H. Page Award: American Heart Association - Honorable Mention
1986 American Society for Clinical Investigation
1992 Mary Rose Swartz Invited Lectureship of the New York Dietetic Association
1996 American Association of Physicians
1996 David Rubenstein Lecture of the Canadian Lipid Club
1997 Albert Hogan Memorial Lecture, University of Missouri
American Heart Association Special Recognition Award
Committees and Society Memberships
American Association of Physicians
American Society for Clinical Investigation
American Federation of Clinical Research
American Heart Association: Arteriosclerosis, Thrombosis, and Vascular Biology Council
Council on Arteriosclerosis (Fellow)
Credentials Committee, 1988-1990
Nutrition Committee, 1989-1992
Program Committee, 1990-Present (Chairperson 1993-1996)
Executive Committee, 1994-Present
Vice Chairman, 1999-Present
American Diabetes Association
Council on Complications: Program Chair, 1996-1998
Professional Services Committee, 1998-Present
Fellow, American Association for the Advancement of Science
American Institute of Nutrition: American Society of Clinical Nutrition
New York Heart Association
Nutrition Committee, 1987-1989
Research Committee, 1987-1990
Board of Directors, 1990-1993
Research Council, 1993-1998
New York Diabetes Association
President Clinical Society, 1978-1988
Head, Professional Education Committee, 1988-1992
Board of Directors, 1987-1992
Vice President, Board of Directors, 1993-1994
President, New York Lipid Club
Selected Publications:
1. Liang, J-s., Kim, T., Fang, S., Weissman, A.M., Fisher, E.A., and Ginsberg, H.N. (2003) Overexpression of the tumor autocrine motility factor receptor-gp78, a ubiquitin protein ligase (E3), results in increased ubiquitinylation and decreased secretion of apolipoprotein B100 in Hep G2 cells. J Biol Chem
278:23984-8
2. Ginsberg, H.N. and Fisher, E.A. (2002) Complexity in the secretory pathway: The assembly and secretion of apolipoprotein B-containing lipoproteins. J. Biol. Chem
277:17377-80
3. Siri P., Candela, N., Ko, C., Zhang Y., Eusufzai, S., Ginsberg, H.N., and Huang Li-Shin. (2001) Post-transcriptional stimulation of the assembly and secretion of triglyceride-rich apolipoproteinB-lipoproteins in a mouse with selective deficiency of brown adipose tissue, obesity and insulin resistance. J Biol Chem
276:46064-72
4. Liang, J-S., Distler, O., Cooper, D, Jamil, H., Deckelbaum, R.J., Ginsberg, H.N. and Sturley, S.J. (2001) HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: A potential mechanism for protease inhibitor-induced hyperlipidemia. Nature Medicine
7:1327-31
5. Mitchell, D.M., Zhou, M., Pariyarath, R. Wang, H., Aitchison, J.D. Ginsberg, H.N. and Fisher, E.A. (1998) Apoprotein B has a prolonged interaction with the translocon during which its lipidation and translocation changes from MTP-dependent to MTP-independent. Proc. Natl. Acad. Sci. USA.
95:14733-8
6. Zhou, M.Y., Fisher, E.A., Ginsberg, H.N. (1998) Regulatable co-translational ubiquitination of apolipoprotein B:100: A new paradigm for proteasomal degradation of a secretory protein. J. Biol. Chem.
38:24649-53
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