Lanlan Shen, M.D.
Lanlan Shen, M.D.
- Associate Professor
Baylor College of Medicine
Houston, TX US
Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
- Advanced Training from MD Anderson Cancer Center
- 01/2003 - Houston, TX United States
- Advanced Training from Johns Hopkins Hospital
- 01/1999 - Baltimore, MD United States
- Ph.D. from Shanghai Second Medical College
- 01/1997 - Shanghai, China, People's Rep
- MD from Zhenjiang Medical School
- 01/1992 - Zhengjiang, China, People's Rep
- Epigenetics, Development and Human Disease
Professional StatementMy laboratory is interested in the epigenetic mechanisms in health and disease with a focus on transcriptional regulation by DNA methylation across development and during tumorigenesis. We use a combination of genomics, epigenomics, and next-generation gene editing approaches and a variety of model systems including cell culture, ex vivo organoids, germ-free and gnotobiotic mice.
p16 Epimutation: Function in Tumorigenesis and As A Target for Cancer Therapy. p16 (or p16INK4a) is a tumor suppressor gene that regulates cell cycle. p16 epimutation - inactivation of p16 by promoter DNA methylation - is one of the most common epigenetic events in human colorectal cancer. We published the first mouse model of targeted p16 promoter methylation (J Clin Invest. 2014; 124:3708). Using these mice, we demonstrate that engineered p16 epimutation drives spontaneous tumor development. Recently, our studies have revealed that p16 epimutation operates synergistically with mutant K-ras and Apc(Min) to promote lung and colon tumor progression. Our overall goals are to understand epigenetic causality of human cancers and to identify epigenetic vulnerabilities that can be targeted for therapeutic intervention.
Gut Microbiota and Developmental Epigenetic Regulation of Intestinal Stem Cells. We are interested in understanding how DNA methylation processes interplay with environmental cues (nutrition and microbiota) to guide the emergence and behavior of intestinal stem cells (ISCs). Using mouse models, we demonstrate that the suckling period is critical for epigenetic changes in the development of ISCs, potentially affecting intestinal health for life (Genome Biol. 2015; 16:211). We show that postnatal intestinal epigenetic regulation is significantly altered by germ-free conditions. Interestingly, the successful restoration of DNA methylation depends on the timing of microbial colonization (i.e. pre-weaning vs. after-weaning), supporting a critical window phenomenon. Currently, we are applying state-of-the-art sequencing-based techniques to achieve the ultimate genome-wide, unbiased assessment of microbial effects on ISC epigenome. We are using cutting-edge genome editing to dissect the epigenetic mechanisms that regulate ISC function in response to the gut microbiota. Our ultimate goal is to develop epigenetically targeted probiotic therapies to provide lifelong protection against intestinal disease.
- Parikh N, Shuck RL, Gagea M, Shen L, Donehower LA. "Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice.." 2018 : Pubmed PMID: 29047229
- Schraw JM, Yiu TT, Lupo PJ, Tsavachidis S, Rau R, Bondy ML, Rabin KR, Shen L, Scheurer ME. "Maternal folate genes and aberrant DNA hypermethylation in pediatric acute lymphoblastic leukemia." : Pubmed PMID: 29763473
- Iqbal NT, Syed S, Sadiq K, Khan MN, Iqbal J, Ma JZ, Umrani F, Ahmed S, Maier EA, Denson LA, Haberman Y, McNeal MM, Setchell KDR, Zhao X, Qureshi S, Shen L, Moskaluk CA, Liu TC, Yilmaz O, Brown DE, Barratt MJ, Kung VL, Gordon JI, Moore SR, Ali SA. "Study of Environmental Enteropathy and Malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation.." 2019 : Pubmed PMID: 31331393
- Deng F, Zhou H, Lin Y, Heim JA, Shen L, Li Y, Zhang L. "Predict multicategory causes of death in lung cancer patients using clinicopathologic factors.." 2021 : Pubmed PMID: 33307409
- Deng F, Shen L, Wang H, Zhang L. "Classify multicategory outcome in patients with lung adenocarcinoma using clinical, transcriptomic and clinico-transcriptomic data: machine learning versus multinomial models.." 2021 : Pubmed PMID: 33415023
- Alves da Silva, A. V., de Castro Oliveira, S. B., Di Rienzi, S. C., Brown-Steinke, K., Dehan, L. M., Rood, J. K., Carreira, V. S., Le, H., Maier, E. A., Betz, K. J., Aihara, E., Ley, R. E., Preidis, G. A., Shen, L., and Moore, S. R. "Murine Methyl Donor Deficiency Impairs Early Growth in Association with Dysmorphic Small Intestinal Crypts and Reduced Gut Microbial Community Diversity." 2018 :
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