- Associate Professor
- Baylor College of Medicine
- Houston, TX, US
- Advanced Training from M.D. Anderson Cancer Center
- Advanced Training from Johns Hopkins Hospital
- Ph.D. from Shanghai Second Medical College
- MD from Zhenjiang Medical School
- Epigenetics, Development and Human Disease
My research is focused on understanding the developmental origins of cancer from an epigenetic perspective. The developmental origins paradigm has been investigated intensively with regards to cardiovascular disease, type 2 diabetes, and obesity. This area of research, however, has been much less emphasized in cancer, despite the fact that early environmental influences on epigenetics is now viewed as one of the mechanisms most likely to underlie the developmental origins of chronic disease, and cancer is the chronic disease in which epigenetic dysregulation is most clearly implicated. Although the importance of DNA methylation in cancer is widely accepted, important outstanding questions remain: How is genome-wide DNA methylation established and maintained during various developmental stages? How are developmental epigenetic mechanisms of gene regulation influenced by “nutritional programming”? How do epigenetic aberrations induced by environmental exposures lead to carcinogenesis?
To understand fundamental mechanisms regulating DNA methylation during development, our research team has been using stem cells and/or mice as model systems. We have established genome-wide methods for DNA methylation analysis using ‘next generation’ sequencing technology. We have recently developed and validated an ‘epigenetic engineering’ approach for targeted DNA methylation in mice. This research will provide novel insights into the fundamental processes of development and how these processes are influenced by diet, nutrition and other factors.
- Yu DH, Gadkari M, Zhou Q, Yu S, Gao N, Guan Y, Schady D, Roshan TN, Chen MH, Laritsky E, Ge Z, Wang H, Chen R, Westwater C, Bry L, Waterland RA, Moriarty C, Hwang C, Swennes AG, Moore SR, Shen L.. "Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome.." Genome Biol.. 2015 September 30;16:211. Pubmed PMID: 26420038
- Yu DH, Waterland RA, Zhang P, Schady D, Chen MH, Guan Y, Gadkari M, Shen L.. "Targeted p16Ink4a epimutation causes tumorigenesis and reduces survival in mice.." J Clin Invest.. 2014;124(9):3708-12. Pubmed PMID: 25061879
- Yu DH, Ware C, Waterland RA, Zhang J, Chen MH, Gadkari M, Kunde-Ramamoorthy G, Nosavanh LM, Shen L. "Developmentally programmed 3' CpG island methylation confers tissue- and cell-type-specific transcriptional activation.." Mol. Cell. Biol.. 2013 May;33(9):1845-58. Pubmed PMID: 23459939
- Shen L, Kantarjian H, Guo Y, Lin E, Shan J, Huang X, Berry D, Ahmed S, Zhu W, Pierce S, Kondo Y, Oki Y, Jelinek J, Saba H, Estey E, Issa JP. "DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes.." J. Clin. Oncol.. 2010 February 1;28(4):605-13. Pubmed PMID: 20038729
- 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 October;3(10):2023-36. Pubmed PMID: 17967063