Upasna Sharma

Assistant Professor of MCD Biology

B.Sc. & M.Sc., University of Delhi, Delhi, India

Ph.D., Wesleyan University, Middletown, CT

Postdoctorate, University of Massachusetts Medical School, Worcester MA

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.

Please follow this link to find the lab's publications in the National Library of Medicine's PubMed database.