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Bluma Lesch, MD, PhD

Associate Professor of Genetics and of Obstetrics, Gynecology, and Reproductive Sciences

Research Summary

Germ cells (sperm, eggs, and their developmental precursors) carry the genome from one generation to the next. The encoded information will first guide the development of the next generation and then be passed to future generations to ensure species continuity. How germ cells handle the physical genome therefore has significant implications for development of individuals and for evolution of species. Our lab aims to define how packaging of the genome in germ cells influences these processes. We compare chromatin states in germ cells across species to understand how genome regulation has evolved, and we use mouse genetics to model the molecular basis of these processes and their direct effects on embryo development across generations.

We are especially interested in epigenetic poising, a chromatin state characterized by the simultaneous presence of both activating and repressive histone marks and strongly associated with pluripotency in stem cells and germ cells. We previously showed that poising is a fundamental characteristic of mammalian germ cells beginning at early stages of development and specifically marks genes required for embryogenesis in the next generation. Furthermore, poising is conserved in the germ lines of mammals and birds, but diverges at specific locations in individual lineages in conjunction with lineage-specific developmental innovations. These findings imply that poising in the germ line may help to protect or ‘set aside’ regions of the genome that are particularly important for early embryonic development. We are currently pursuing this hypothesis. We are also exploring how other unique aspects of germ cell chromatin regulation impact offspring phenotype transgenerationally, and how these germline-specific mechanisms can become aberrantly activated in diseases such as cancer. (Please see the lab website for more information about current projects.)


Research Interests

Embryonic and Fetal Development; Gene Expression Regulation; Germ Cells; Reproduction; Stem Cells; Evolution, Molecular; Computational Biology; Heredity; Chromatin Assembly and Disassembly; Epigenetic Memory

Selected Publications