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Last Updated: 3/30/2009
| Steven H Zeisel, MD, PhD
Kenan Distinguished University Professor |  |
Research Interests
Dr. Zeisel's research focuses on the human nutrient requirements for choline and the role of one carbon metabolism in stem cell proliferation and cell suicide (apoptosis). When rodents are deprived of choline they spontaneously develop cancer. Dr. Zeisel's research team has been characterizing the human dietary requirement for choline. When humans are deprived of choline most people develop fatty liver with increased rates of cell suicide in liver and other tissues. Choline can be derived from the diet as well as from endogenous production in the liver (catalyzed by the enzyme PEMT). The gene for PEMT has a series of estrogen response elements in its promoter, and the gene is induced by estrogen. Thus most young women need little dietary choline while men and post menopausal must eat this nutrient or become sick. Dr. Zeisel's research team discovered that 45% of women have a genetic variation (snp) in the PEMT gene that makes them unresponsive to estrogen and therefore they require dietary choline. The team also found that the current recommended intake of 550 mg/day was too low for 10% of men, who need 850 mg/day He is continuing these investigations identifying snps in humans that occur commonly and change the dietary requirements for choline. This has relevance for cancer research as individuals with increased requirements for choline may be more susceptible to cancer. Working with the Long Island Breast Cancer study (more than 18000 women followed for breast cancer), Dr. Zeisel found that women with a snp in PEMT have a 30% increased risk of breast cancer. His research team currently is using mice in which the genes of choline metabolism have been altered to determine if variation in these genes increases cancer risk. In a separate line of investigation, Dr. Zeisel's team discovered that choline availability during a 5 day period in gestation alters DNA (CpG) methylation and histone methylation in the promoter of a number of genes that regulate cell proliferation and that choline availability directly modifies the rate at which hippocampal stem cells proliferate. These epigenetic effects of choline may explain it effect on carcinogenesis.
Recent Accomplishments and Honors
Director, Nutrition Research Institute, University of North Carolina, 2006 - present
Associate Dean for Research, School of Public Health, UNC, 1999-2007.
Professor, Department of Pediatrics, University of North Carolina, 1990 - present.
Member, Editorial Board, FASEB Journal, 2005-present
Member, Editorial Committee, Annual Review of Nutrition, 2005-2008
FDA Food Advisory Committee, Center for Food Safety & Applied Nutrition, Dietary Supplements, 2001 - 2005
Chairman NIH Integrative Nutrition and Metabolic Processes study section, 2000 - 2009
Member, Board of Scientific and Policy Advisors, American Council on Science and Health, 2000 - present
International Society for Research for Human Milk and Lactation, 1998 - present
International Society for Neurochemistry, 1998 - present
Panel on Recommended Dietary Intake of Folate and B-vitamins, National Academy of Sciences, 1996 - 1998
American Society for Clinical Nutrition, Councilor, 1991 - 1994
1990-present American Society for Parenteral and Enteral Nutrition, 1990 - present
American College of Nutrition, 1988 - present
Society for Pediatric Research, 1987 - present
American Society for Nutritional Sciences, (President 2002) and Long Range Planning Chair, 2003-2005, 1987 - 2005.
Honors
2009 - W.O. Atwater Lecturer - U.S. Department of Agriculture's Agricultural Research Service
2008 - The American Society for Nutrition Osborne and Mendel Award
2007 - The American College of Nutrition Award for Outstanding Achievements in Nutrition
2006 - Bristol-Meyers Squibb/Mead Johnson Award for Distinguished Achievement in Nutrition
Research
2005- IFN/CERH Distinguished Lectureship, Texas A&M
2004-present Who's Who in the World
Publications
1. Zeisel, S.H. (2009) Epigenetic mechanisms for nutrition determinants of later health outcome. American Journal of Clinical Nutrition [IN PRESS].
2. Zeisel, S.H. (2008) Genetic polymorphisms in methyl-group metabolism and epigenetics: Lessons from humans and mouse models. Brain Research 1237:5-11.
3. Pop, E., Fischer, L. Gitzinger, M., Coan, A. and Zeisel, S.H. (2008) Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis and estrogenic outcomes in healthy postmenopausal women-a Phase I clinical trial. Menopause 15(4 Pt 1):684-92.
4. Xu, X., Gammon, M.D., Zeisel, S.H., Lee, Y.L., Wetmur, J.G., Teitelbaum, S.L., Bradshaw, P., Neugut, A.I., Santella, R.M., and Chen, J. (2008) Choline Metabolism and Risk of Breast Cancer in population-based study. FASEB Journal 22(6):2045-52.
5. Cho, E., Willett, W., Colditz, G., Fuchs, C., Wu, K., Chan, A., Zeisel, S.H., and Giovannucci, E. (2007) Dietary Choline and Betaine and the Risk of Distal Colorectal Adenoma in Women. Journal of the National Cancer Institute 99:1224-1231.
6. da Costa, K-A., Kozyrez, O.G., Song, J., Galanko, J.A., Fischer, L.M., and Zeisel, S.H. (2006) Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB Journal 20:1336-1344.
7. Kohlmeier, M., da Costa, K-A., Fischer, L., and Zeisel, S.H. (2005) Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proceedings of the National Academy of Sciences 102(44): 16025-16030.
E-mail: steven_zeisel@unc.edu
Telephone: (919) 843-4731
FAX: 919-843-8555
Address: 2115A Michael Hooker Research Center, CB# 7461 Chapel Hill, NC 27599-7461
