Lanlan Shen, M.D., Ph.D.
Associate Professor, Baylor College of Medicine
M.D., Medicine, Zhenjiang Medical School (Currently known as Jiangsu University School of Medicine), Zhenjiang, P. R. China
Ph.D., Gastroenterology and Hepatology, Shanghai Second Medical University, Shanghai, P. R. China
Postdoctoral Fellow, Johns Hopkins University School of Medicine, Baltimore, MD
Postdoctoral Fellow, Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX
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 recently been developing two model systems: embryonic stem cells and a transgenic mouse model. We have established genome-wide methods for DNA methylation analysis using microarray and ‘next generation’ sequencing technology. This research will provide novel insights into the fundamental processes of development and how these processes are influenced by diet, nutrition and other factors.
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. 2009, 28(4): 605-613.
Ware CB, Wang L, Mecham BH, Shen L, Nelson AM, Bar M, Lamba DA, Dauphin DS, Buckingham B, Askari B, Lim R, Tewari M, Gartler SM, Issa JP, Pavlidis P, Duan Z, Blau A. Histone deacetylases inhibition elicits an evolutionarily conserved self renewal program in embryonic stem cells. Cell Stem Cell. 2009, 4 (4): 359-69.
Waterland RA, Kellermayer R, Rached MT, Tatevian N, Gomes MV, Zhang J, Zhang L, Chakravarty A, Zhu W, Laritsky E, Zhang W, Wang X, Shen L. Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development. Human Mol Genet. 2009, 18(16): 3026-38.
Kondo Y, Shen L, Cheng A, Ahmed S, Boumber Y, Charo C, Yamochi T, Urano T, Furukawa K, Kwabi-Addo B, Gold D, Sekido Y, Huang T, Issa JPJ. Gene silencing in cancer by histone H3 lysine 27 tri-methylation independent of promoter DNA methylation. Nat Genet. 2008, 40 (6): 741-50.
Shen L, Kondo Y, Guo Y, Zhang J, Zhang L, Ahmed S, Shu J, Chen X, Waterland RA, Issa JPJ. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet. 2007, 3(10): 2023-2036.