Sharma, Upasna - University of California, Santa Cruz - Molecular, Cell & Developmental Biology Faculty

个人简介

B.Sc. & M.Sc., University of Delhi, Delhi, India Ph.D., Wesleyan University, Middletown, CT Postdoctorate, University of Massachusetts Medical School, Worcester MA

研究领域

RNA-mediated intergenerational inheritance Inheritance of phenotypic changes in the absence of changes in DNA sequence is known as epigenetic inheritance, and is essential for cell state maintenance during cell division. During sexual reproduction, not only do we pass genetic information to our progeny, some epigenetic information is also transmitted to the offspring. A major implication of gametic epigenetic inheritance is that, because epigenetic modifications are often regulated by environmental conditions, the environment experienced by parents could potentially influence the phenotype of offspring via alterations to the gamete “epigenome.” Furthermore, the transmission of paternal environmental information to the offspring could in principle be adaptive. Indeed, multiple studies in mammals (human and rodent models) have demonstrated that parental dietary alteration leads to metabolic phenotypes in the progeny. Despite this wealth of information, the mechanism of such intergenerational inheritance remains mostly unknown. There is growing evidence that epigenetic effects of paternal conditions are transmitted via sperm, raising the question of which epigenetic information carrier in sperm is responsible for the transmission of environmental information? Small RNAs play key roles in multiple well-established epigenetic inheritance paradigms in various model organisms. We and others have previously demonstrated that small RNAs in sperm respond to environmental conditions, such as diet, stress, alcohol and chemical treatment. Although these studies provide strong evidence that small RNAs in sperm potentially represent environmentally-responsive epigenetic marks in the germline, we currently lack any mechanistic understanding of the biogenesis and function of small RNAs in sperm. Using a combination of molecular, biochemical, cytological and genomic techniques, our lab is interested in characterizing the molecular machinery responsible for the generation of small RNAs in mature sperm and investigating how exposure of an organism to various environmental conditions alters/reprograms sperm epigenome.

近期论文

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Small RNAs Are Trafficked from the Epididymis to Developing Mammalian Sperm. Sharma U, Sun F, Conine CC, Reichholf B, Kukreja S, Herzog VA, Ameres SL, Rando OJ. Developmental cell. 2018; 46(4):481-494.e6. NIHMSID: NIHMS979038 A synthetic biology approach to probing nucleosome symmetry. Ichikawa Y, Connelly CF, Appleboim A, Miller TC, Jacobi H, Abshiru NA, Chou HJ, Chen Y, Sharma U, Zheng Y, Thomas PM, Chen HV, Bajaj V, Müller CW, Kelleher NL, Friedman N, Bolon DN, Rando OJ, Kaufman PD. Metabolic Inputs into the Epigenome. Sharma U, Rando OJ. Cell metabolism. 2017; 25(3):544-558. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, Belleannee C, Kucukural A, Serra RW, Sun F, Song L, Carone BR, Ricci EP, Li XZ, Fauquier L, Moore MJ, Sullivan R, Mello CC, Garber M, Rando OJ. Science (New York, N.Y.). 2016; 351(6271):391-396. NIHMSID: NIHMS780640 Father-son chats: inheriting stress through sperm RNA. Sharma U, Rando OJ. Cell metabolism. 2014; 19(6):894-5. NIHMSID: NIHMS600702 Histone variant H2A.Z functions in sister chromatid cohesion in Saccharomyces cerevisiae. Sharma U, Stefanova D, Holmes SG. Molecular and cellular biology. 2013; 33(17):3473-81. H2A.Z (Htz1) controls the cell-cycle-dependent establishment of transcriptional silencing at Saccharomyces cerevisiae telomeres. Martins-Taylor K, Sharma U, Rozario T, Holmes SG. Genetics. 2011; 187(1):89-104.