BBS Faculty Member - Yujiang Geno Shi

Yujiang Geno Shi

Department of Biological Chemistry and Molecular Pharmacology

Brigham and Women's Hospital, Division of Endocrinology
Hypertension and Diabetes
221 Longwood Avenue EBRC 222A
Boston, MA 02115
Tel: 617-525-8097
Fax: 617-732-5764
Email: yujiang_shi@hms.harvard.edu



The long-term goal of Y. Geno Shi’s research is to understand how processing of human genomic information is controlled epigenetically through chromatin modifications and how dysregulation of these epigenetic events contributes to complex human diseases. It is becoming clear that epigenetic changes including alterations of chromatin modifications provide a key mechanism for regulating the diverse structural and functional features of chromatin, including control of gene regulation and maintenance of genomic integrity. These play critical roles in cell growth and survival, differentiation, embryonic development, and their related pathologies, including oncogenic transformation. In particular, we are interested in exploring novel mechanisms involved in regulation of eukaryotic gene expression. Mainly we try to understand how dynamic and coordinated changes of chromatin modifications including histone modification and DNA methylation (“epigenetic codes”) regulate gene expression in eukaryotic cells. We seek to identify novel epigenetic regulators and characterize their roles in controlling the patterns of epigenetic codes during normal cell differentiation and tissue development. We also try to understand how perturbation of these epigenetic processes could lead to complex human diseases.

Increasing evidence suggests that histone methylation, the most abundant and important histone modification, plays a critical role in human cancer and other complex diseases, such as neurological disorders. Our finding of the first histone demethylase, LSD1, and the subsequent identification of other histone demethylases have brought a conclusion to the long held debate that histone methylation is dynamically regulated by both histone methylases and demethylases. It is not surprising that many key questions pertaining to the biology of histone demethylases and their roles in epigenetics remain. Our current research program is centered on these questions and is primarily based on histone demethylases discovered either by myself, while a postdoc (LSD1) or within my laboratory (LSD2 and SMCX/Jarid1C). Specifically, we are exploring the biological functions and clinical implications of the histone demethylases, understanding how histone demethylases are regulated by cellular factors and metabolic signals, and developing translational research on the newly discovered demethylases. We hope that the output from our research will not only make significant contributions but also further our understanding of the biology of newly discovered histone demethylases, their relevance, and impact in the advancement of human health.



Last Update: 8/22/2013



Publications

Tahiliani M, Mei P, Fang R, Leonor T, Rutenberg M, Shimizu F, Li J, Rao A & Yujiang Shi*. The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature. 2007 May 31; 447(7144): 601-5

Yujiang Shi, Lan F, Matson CA, Peter Mulligan, Whetstine JR, Cole PA, Casero RA and Shi Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell Dec. 29, 2004.

Yujiang Shi and Yang Shi. Metabolic enzymes and coenzymes in transcription—a direct link between metabolism and transcription? Trends Genet. 2004 20(9):445-52.

Yujiang Shi, Sawada J, Sui G, Affar el B, Whetstine JR, Lan F, Ogawa H, Luke MP, Nakatani Y, Shi Y. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature 2003 Apr 17;422(6933):735-8.



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