MD, PhD
Kenan Distinguished Professor, Nutrition
Director, Nutrition Research Institute
UNC-Chapel Hill
Cancer Epidemiology
Area of Interest
The research of Steven H. Zeisel, MD, PhD, 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. Mice with the BHMT gene deleted (a gene in choline metabolism) spontaneously develop liver cancers. 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. 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), 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, 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.
Awards and Honors
- Bernard G. Greenberg Alumni Endowment Award, UNC-Chapel Hill, 2013
- Mildred A. Reeves Distinguished Visiting Professor in Nutrition, University of Tennessee, 2011
- W.O. Atwater Lecturer – U.S. Department of Agriculture’s Agricultural Research Service, 2009
- The American Society for Nutrition Osborne and Mendel Award, 2008
- The American College of Nutrition Award for Outstanding Achievements in Nutrition, 2007
- Bristol-Meyers Squibb/Mead Johnson Award for Distinguished Achievement in Nutrition Research, 2006
- IFN/CERH Distinguished Lectureship, Texas A&M, 2005
- Who’s Who in the World, 2004-present
