DIET, DNA METHYLATION PROCESSES AND HEALTH WORKSHOP

Agenda

Monday, August 6, 2001

Welcome and Opening Remarks Session

8:00 to 8:30 AM

Ruth Kirschstein, M.D., Principle DeputyDirector, National Institutes of Health

Bernard Schwetz, D.V.M., Ph.D., Acting Principal Deputy Commissioner, Food and Drug Administration

Richard Allison, Ph.D., Executive Officer, American Society for Nutritional Sciences

Richard Black, Ph.D., Executive Director, International Life Sciences Institute of North America

Overview Topics
Moderator: Lionel Poirier, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR.

8:30 to 8:55 AM DNA methylation in mammals. Peter A. Jones, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA.

8:55 to 9:20 AM Metabolic aspects of methyl group formation from one-carbon units. Barry Shane, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA.

9:20 to 9:45 AM Diet and methyl donors: interactions between dietary folate, methionine, and choline. Steven Zeisel, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.

9:45 to 10:10 AM Impact of nutrition, genetics, and chemical toxicity on aberrant DNA methylation. Lionel Poirier, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR.

10:10 to 10:30 AM Discussion

10:30 to 10:50 AM Morning Break

Dietary Methyl Donor Insufficiency and Human Disease Risk
Moderator: John Milner, Division of Cancer Prevention, National Cancer Institute, Rockville, MD.

10:50 to 11:15 AM Cellular vitamins, DNA methylation and cancer risk. Gary L. Johanning and Chandrika J. Piyathilake,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL.

11:15 to 11:40 AM Nutritional and genetic inefficiencies in one-carbon metabolism and cervical cancer risk. Regina Ziegler, Division of Cancer Epidemiology and Biostatistics, National Cancer Institute, Rockville, MD.

11:40 to 12:05 PM Interactions between folate-B12-alcohol-methioine and cancer risk. Edward Giovannucci, Channing Laboratory, Department of Medicine, Harvard Medical School, and Department of Nutritional Epidemiology, Harvard School of Public Health, Boston, MA.

12:05 to 12:30 PM Folic acid supplementation and prevention of neural tube defects. Nancy S. Green, March of Dimes, White Plains, NY.

12:30 to 12:50 PM Discussion

12:50 to 1:50 PM Lunch Break (Lunch is on your own)

Methyl Metabolism and Biochemistry
Moderator: S. Jill James, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR.

1:50 to 2:15 PM Elevated homocysteine levels and DNA hypomethylation: an epigenetic mechanism for homocysteine-related pathology. S. Jill James, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR.

2:15 to 2:40 PM Metabolic interaction of alcohol and folate. Charles Halsted, Division of Clinical Nutrition and Metabolism, University of California School of Medicine, Davis, CA.

2:40 to 3:05 PM Vitamin B12, folate, and methylation reactions in the brain. Ralph Green, Department of Medical Pathology, University of California, Davis, CA.

3:05 to 3:25 PM Afternoon Break

3:25 to 3:50 PM Abnormal methyl metabolism in pancreatic toxicity and diabetes. Daniel Longnecker, Department of Pathology, Dartmouth Medical School, Lebanon, NH.

3:50 to 4:15 PM The suppression of methionine adenosyltransferase IA in hepatotoxicity. José M. Mato, Unidad de Hepatologia y Terapia Genica, Departamento de Medicina Interna, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain.

4:15 to 4:40 PM Gene-nutrient interactions and DNA methylation. Jacob Selhub, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA.

4:40 to 5:00 PM Discussion

Tuesday, August 7, 2001

Mechanisms and Consequences of (Aberrant) DNA Methylation in Physiological Processes

Moderator: John Potter, Fred Hutchinson Cancer Research Center, Seattle, WA.

9:00 to 9:25 AM DNA methylation and imprinting in development. Benjamin Tycko, Institute of Cancer Genetics, Columbia University, New York, NY.

9:25 to 9:50 AM Epigenetic variation and human disease. Jean-Pierre Issa, Leukemia Department, University of Texas at M.D. Anderson Cancer Center,Houston, TX.

9:50 to 10:15 AM Maternal dietary methyl supplements increase DNA methylation and methylation-dependent phenotype in mammalian offspring. Craig Cooney, Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR.

10:15 to 10:40 AM Role of DNA methylation in the regulation of cell function: cancer, autoimmunity, and aging. Bruce Richardson, Internal Medicine, University of Michigan at Ann Arbor, Ann Arbor, MI.

10:40 to 11:00 AM Morning Break

11:00 to 11:25 AM DNA methylation and atherosclerosis. Pascal J. Goldschmidt, Division of Cardiology, Duke University Medical Center, Durham, NC.

11:25 to 11:50 AM Methyl supply and methyl metabolizing enzymes and colon cancer risk. John Potter, Fred Hutchinson Cancer Research Center, Seattle, WA.

11:50 to 12:15 PM Folate deficiency and colon carcinogenesis: hypomethylation of p53, DNA strand breaks and DNA repair. Joel Mason, Vitamin and Carcinogenesis Program, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA.

12:15 to 1:15 PM Lunch Break

Mechanisms and Consequences of (Aberrant) DNA Methylation in Physiological Processes, continued Moderator: John Potter

1:15 to 1:40 PM Effects of phytoestrogens on DNA methylation in mice and in the TRAMP mouse prostate cancer model. Dennis Lubahn, Departments of Biochemistry and Child Health, University of Missouri-Columbia, Columbia, MO.

1:40 to 2:05 PM DNA hypomethylation: the ICF syndrome, immunodeficiency, DNA rearrangements, and cancer. Melanie Ehrlich, Human Genetics Program, Tulane Cancer Center at Tulane Medical School, New Orleans, LA.

2:05 to 2:25 PM Discussion

2:25 to 2:45 PM Afternoon Break

Research Applications in DNA Methylation
Moderator: Peter Laird, Keck School of Medicine, University of Southern California, Los Angeles, CA.

2:45 to 3:10 PM Current methodologies in DNA methylation analysis. Peter Laird, Keck School of Medicine, University of Southern California, Los Angeles, CA.

3:10 to 3:35 PM Dissecting complex epigenetic alterations in cancer using CpG island microarray. Tim Huang, Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri-Columbia, Columbia, MO.

3:35 to 4:00 PM A public DNA methylation database. Christoph Grunau, Institut de Genetique humaine, Montpellier, France.

4:00 to 4:25 PM Efficient detection of DNA methylation patterns. Alexander Olek, Epigenomics AG, Berlin, Germany.

4:25 to 4:45 PM Discussion

Wednesday, August 8, 2001

8:00 to 8:10 AM In Tribute to Dr. Alan Wolffe

Cell and Molecular Biology of DNA Methylation
Moderator: Stephen Baylin, The Johns Hopkins University School of Medicine, Baltimore, MD.

8:10 to 8:35 AM Promoter-region methylation and gene silencing in cancer. Stephen Baylin, Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, MD.

8:35 to 9:00 AM Impact of folate deficiency on DNA stability. Susan J. Duthie, Rowett Research Institute, Aberdeen, Scotland, UK.

9:00 to 9:25 AM DNA methylation, histone deacetylation, and gene expression. Fyodor Urnov, Sangamo BioSciences, Richmond, CA.

9:25 to 9:50 AM Folate transport knockout mice, DNA methylation and congenital defects. Richard Finnell, Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, Houston, TX.

9:50 to 10:10 AM Morning Break

10:10 to 10:35 AM Functions of mammalian DNA methyltransferases: lessons learned from mouse knockout models. Masaki Okano, Cardiovascular Research Center, Massachusetts General Hospital-East, Department of Medicine, Harvard Medical School, Charlestown, MA.

10:35 to 11:00 AM DNA methylation and methyl-binding proteins in development and gene regulation. Laurie Jackson-Grusby, Whitehead Institute for Biomedical Research, Cambridge, MA.

11:00 to 11:20 AM Discussion

Public Health Issues
Moderator: Elizabeth Yetley, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC.

11:20 to 11:45 AM Folic acid fortification, folate status and plasma homocysteine. Jeanne Rader, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC.

11:45 to 12:10 PM Biomarker as a competing technology in health services. Sudhir Srivastava, Division of Cancer Prevention, National Cancer Institute, Rockville, MD.

12:10 to 1:10 PM Lunch Break

Public Health Issues, continued
Moderator: Elizabeth Yetley

1:10 to 1:35 PM Bringing individuality to public health recommendations. Patrick Stover, Division of Nutritional Biochemistry, Cornell University, Ithaca, NY.

1:35 PM to 2:00 PM Communicating public health recommendations for consumers. Sylvia Rowe, International Food Information Council, Washington, DC.

2:00 PM to 2:20 PM Discussion

Panel Discussion
Moderator: Sharon Ross, Division of Cancer Prevention, National Cancer Institute, Rockville, MD.

2:20 to 3:20 PM All Session Moderators. Priorities for Future Research: Moderators will summarize each speaker's recommendation for future research and a discussion with all participants about research priorities will follow.

3:20 PM Adjournment

	DIET, DNA METHYLATION PROCESSES AND HEALTH WORKSHOP Agenda Monday, August 6, 2001 Welcome and Opening Remarks Session 8:00 to 8:30 AM Ruth Kirschstein, M.D., Principle DeputyDirector, National Institutes of Health Bernard Schwetz, D.V.M., Ph.D., Acting Principal Deputy Commissioner, Food and Drug Administration Richard Allison, Ph.D., Executive Officer, American Society for Nutritional Sciences Richard Black, Ph.D., Executive Director, International Life Sciences Institute of North America Overview Topics Moderator: Lionel Poirier, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR. 8:30 to 8:55 AM DNA methylation in mammals. Peter A. Jones, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA. 8:55 to 9:20 AM Metabolic aspects of methyl group formation from one-carbon units. Barry Shane, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA. 9:20 to 9:45 AM Diet and methyl donors: interactions between dietary folate, methionine, and choline. Steven Zeisel, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. 9:45 to 10:10 AM Impact of nutrition, genetics, and chemical toxicity on aberrant DNA methylation. Lionel Poirier, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR. 10:10 to 10:30 AM Discussion 10:30 to 10:50 AM Morning Break Dietary Methyl Donor Insufficiency and Human Disease Risk Moderator: John Milner, Division of Cancer Prevention, National Cancer Institute, Rockville, MD. 10:50 to 11:15 AM Cellular vitamins, DNA methylation and cancer risk. Gary L. Johanning and Chandrika J. Piyathilake,Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL. 11:15 to 11:40 AM Nutritional and genetic inefficiencies in one-carbon metabolism and cervical cancer risk. Regina Ziegler, Division of Cancer Epidemiology and Biostatistics, National Cancer Institute, Rockville, MD. 11:40 to 12:05 PM Interactions between folate-B12-alcohol-methioine and cancer risk. Edward Giovannucci, Channing Laboratory, Department of Medicine, Harvard Medical School, and Department of Nutritional Epidemiology, Harvard School of Public Health, Boston, MA. 12:05 to 12:30 PM Folic acid supplementation and prevention of neural tube defects. Nancy S. Green, March of Dimes, White Plains, NY. 12:30 to 12:50 PM Discussion 12:50 to 1:50 PM Lunch Break (Lunch is on your own) Methyl Metabolism and Biochemistry Moderator: S. Jill James, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR. 1:50 to 2:15 PM Elevated homocysteine levels and DNA hypomethylation: an epigenetic mechanism for homocysteine-related pathology. S. Jill James, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR. 2:15 to 2:40 PM Metabolic interaction of alcohol and folate. Charles Halsted, Division of Clinical Nutrition and Metabolism, University of California School of Medicine, Davis, CA. 2:40 to 3:05 PM Vitamin B12, folate, and methylation reactions in the brain. Ralph Green, Department of Medical Pathology, University of California, Davis, CA. 3:05 to 3:25 PM Afternoon Break 3:25 to 3:50 PM Abnormal methyl metabolism in pancreatic toxicity and diabetes. Daniel Longnecker, Department of Pathology, Dartmouth Medical School, Lebanon, NH. 3:50 to 4:15 PM The suppression of methionine adenosyltransferase IA in hepatotoxicity. José M. Mato, Unidad de Hepatologia y Terapia Genica, Departamento de Medicina Interna, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain. 4:15 to 4:40 PM Gene-nutrient interactions and DNA methylation. Jacob Selhub, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA. 4:40 to 5:00 PM Discussion Tuesday, August 7, 2001 Mechanisms and Consequences of (Aberrant) DNA Methylation in Physiological Processes Moderator: John Potter, Fred Hutchinson Cancer Research Center, Seattle, WA. 9:00 to 9:25 AM DNA methylation and imprinting in development. Benjamin Tycko, Institute of Cancer Genetics, Columbia University, New York, NY. 9:25 to 9:50 AM Epigenetic variation and human disease. Jean-Pierre Issa, Leukemia Department, University of Texas at M.D. Anderson Cancer Center,Houston, TX. 9:50 to 10:15 AM Maternal dietary methyl supplements increase DNA methylation and methylation-dependent phenotype in mammalian offspring. Craig Cooney, Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR. 10:15 to 10:40 AM Role of DNA methylation in the regulation of cell function: cancer, autoimmunity, and aging. Bruce Richardson, Internal Medicine, University of Michigan at Ann Arbor, Ann Arbor, MI. 10:40 to 11:00 AM Morning Break 11:00 to 11:25 AM DNA methylation and atherosclerosis. Pascal J. Goldschmidt, Division of Cardiology, Duke University Medical Center, Durham, NC. 11:25 to 11:50 AM Methyl supply and methyl metabolizing enzymes and colon cancer risk. John Potter, Fred Hutchinson Cancer Research Center, Seattle, WA. 11:50 to 12:15 PM Folate deficiency and colon carcinogenesis: hypomethylation of p53, DNA strand breaks and DNA repair. Joel Mason, Vitamin and Carcinogenesis Program, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA. 12:15 to 1:15 PM Lunch Break Mechanisms and Consequences of (Aberrant) DNA Methylation in Physiological Processes, continued Moderator: John Potter 1:15 to 1:40 PM Effects of phytoestrogens on DNA methylation in mice and in the TRAMP mouse prostate cancer model. Dennis Lubahn, Departments of Biochemistry and Child Health, University of Missouri-Columbia, Columbia, MO. 1:40 to 2:05 PM DNA hypomethylation: the ICF syndrome, immunodeficiency, DNA rearrangements, and cancer. Melanie Ehrlich, Human Genetics Program, Tulane Cancer Center at Tulane Medical School, New Orleans, LA. 2:05 to 2:25 PM Discussion 2:25 to 2:45 PM Afternoon Break Research Applications in DNA Methylation Moderator: Peter Laird, Keck School of Medicine, University of Southern California, Los Angeles, CA. 2:45 to 3:10 PM Current methodologies in DNA methylation analysis. Peter Laird, Keck School of Medicine, University of Southern California, Los Angeles, CA. 3:10 to 3:35 PM Dissecting complex epigenetic alterations in cancer using CpG island microarray. Tim Huang, Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri-Columbia, Columbia, MO. 3:35 to 4:00 PM A public DNA methylation database. Christoph Grunau, Institut de Genetique humaine, Montpellier, France. 4:00 to 4:25 PM Efficient detection of DNA methylation patterns. Alexander Olek, Epigenomics AG, Berlin, Germany. 4:25 to 4:45 PM Discussion Wednesday, August 8, 2001 8:00 to 8:10 AM In Tribute to Dr. Alan Wolffe Cell and Molecular Biology of DNA Methylation Moderator: Stephen Baylin, The Johns Hopkins University School of Medicine, Baltimore, MD. 8:10 to 8:35 AM Promoter-region methylation and gene silencing in cancer. Stephen Baylin, Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, MD. 8:35 to 9:00 AM Impact of folate deficiency on DNA stability. Susan J. Duthie, Rowett Research Institute, Aberdeen, Scotland, UK. 9:00 to 9:25 AM DNA methylation, histone deacetylation, and gene expression. Fyodor Urnov, Sangamo BioSciences, Richmond, CA. 9:25 to 9:50 AM Folate transport knockout mice, DNA methylation and congenital defects. Richard Finnell, Institute of Biosciences and Technology, The Texas A&M University System Health Science Center, Houston, TX. 9:50 to 10:10 AM Morning Break 10:10 to 10:35 AM Functions of mammalian DNA methyltransferases: lessons learned from mouse knockout models. Masaki Okano, Cardiovascular Research Center, Massachusetts General Hospital-East, Department of Medicine, Harvard Medical School, Charlestown, MA. 10:35 to 11:00 AM DNA methylation and methyl-binding proteins in development and gene regulation. Laurie Jackson-Grusby, Whitehead Institute for Biomedical Research, Cambridge, MA. 11:00 to 11:20 AM Discussion Public Health Issues Moderator: Elizabeth Yetley, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC. 11:20 to 11:45 AM Folic acid fortification, folate status and plasma homocysteine. Jeanne Rader, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC. 11:45 to 12:10 PM Biomarker as a competing technology in health services. Sudhir Srivastava, Division of Cancer Prevention, National Cancer Institute, Rockville, MD. 12:10 to 1:10 PM Lunch Break Public Health Issues, continued Moderator: Elizabeth Yetley 1:10 to 1:35 PM Bringing individuality to public health recommendations. Patrick Stover, Division of Nutritional Biochemistry, Cornell University, Ithaca, NY. 1:35 PM to 2:00 PM Communicating public health recommendations for consumers. Sylvia Rowe, International Food Information Council, Washington, DC. 2:00 PM to 2:20 PM Discussion Panel Discussion Moderator: Sharon Ross, Division of Cancer Prevention, National Cancer Institute, Rockville, MD. 2:20 to 3:20 PM All Session Moderators. Priorities for Future Research: Moderators will summarize each speaker's recommendation for future research and a discussion with all participants about research priorities will follow. 3:20 PM Adjournment



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