Robert Waterland, Ph.D.

Assistant Professor of Pediatrics
Baylor College of Medicine
waterland@bcm.tmc.edu

Research Interests
Representative Publications

Early Nutritional Influences on Mammalian Epigenetic Gene Regulation

There is accumulating evidence that the pathogenesis of many adult-onset chronic diseases, including type 2 diabetes, cardiovascular disease, and cancer, can be influenced by nutrition in early life. One probable underlying mechanism is through early nutritional effects on epigenetics, i.e. self-perpetuating gene regulatory systems that are not dependent on DNA sequence alterations. A particularly relevant epigenetic mechanism involves the methylation of cytosine residues on both strands of palindromic CpG dinucleotides. Mammalian one-carbon metabolism, which provides the methyl groups for biological methylation reactions, is highly dependent on dietary substrates and cofactors. Thus, the establishment and maintenance of genomic methylation patterns during early development may make it more critical to maintain appropriate levels of these diet-derived components at that time than during later life. My laboratory is investigating the overall hypothesis that maternal methyl donor nutrition before conception and during pregnancy alters DNA methylation of specific genomic regions in the early embryo, and that these induced epigenetic alterations persist to adulthood. We are testing this hypothesis in mouse models, focusing on two gene classes: genes adjacent to transposon elements, and genomically imprinted genes. Understanding the specific biologic mechanisms linking early nutrition to adult gene expression and metabolism may ultimately enable early-life nutritional interventions aimed at ameliorating adult-onset chronic disease in humans.

Robert Waterland's lab

Dr. Waterland's's lab

From left to right. Marcus Gomes, Wei Zhu, Rob Waterland, Sherin Mirza, Richard Kellermayer

Representative Publications:

Dion V, Lin Y, Hubert L Jr, Waterland RA, Wilson JH. Dnmt1 deficiency promotes CAG repeat expansion in the mouse germline. Hum Mol Genet. 2008 May 1;17(9):1306-17. Epub 2008 Feb 5. PMID: 18252747 [PubMed - in process] 17967063

Waterland RA, Travisano M, Tahiliani KG. Diet-induced hypermethylation at agouti viable yellow is not inherited transgenerationally through the female. FASEB J. 2007 Oct;21(12):3380-5

Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, Shu J, Chen X, Waterland RA, Issa JP. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet. 2007 Oct;3(10):2023-36. Epub 2007 Sep 10. PMID: 17967063 [PubMed - indexed for MEDLINE]

Waterland RA, Michels KB. Epigenetic Epidemiology of the Developmental Origins Hypothesis. Annu Rev Nutr. 2007 Apr 27; [Epub ahead of print]

Waterland RA. Epigenetic mechanisms and gastrointestinal development. J Pediatr. 2006 Nov;149(5 Suppl):S137-42. Review.

Waterland RA, Dolinoy DC, Lin JR, Smith CA, Shi X, Tahiliani KG. Maternal methyl supplements increase offspring DNA methylation at Axin Fused. Genesis. 2006 Sep;44(9):401-6.

Waterland RA. Does Nutrition during Infancy and Early Childhood Contribute to Later Obesity via Metabolic Imprinting of Epigenetic Gene Regulatory Mechanisms? Nestle Nutr Workshop Ser Pediatr Program. 2005;56:157-74. No abstract available. PMID: 16632951 [PubMed - in process]

Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect. 2006 Apr;114(4):567-72. PMID: 16581547 [PubMed - indexed for MEDLINE]

Waterland RA, Lin JR, Smith CA, Jirtle RL. Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet. 2006 Mar 1;15(5):705-16. Epub 2006 Jan 18. PMID: 16421170 [PubMed - indexed for MEDLINE]

Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 2004 Jan;20(1):63-8. Review. No abstract available. PMID: 14698016 [PubMed - indexed for MEDLINE]

Waterland RA, Jirtle RL. Transposable elements: Targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003 Aug;23(15):5293-300. PMID: 12861015 [PubMed - indexed for MEDLINE]

Waterland RA, Garza C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr. 1999 Feb;69(2):179-97. Review. PMID: 9989679 [PubMed - indexed for MEDLINE]