Bluma Lesch, MD, PhD

Assistant Professor of Genetics

Research Departments & Organizations

Yale Cancer Center: Genomics, Genetics, and Epigenetics

Research Interests

Cellular Reprogramming; Chromatin Assembly and Disassembly; DNA Packaging; Embryonic and Fetal Development; Evolution, Molecular; Fertility; Gene Expression Regulation; Germ Cells; Heredity; Infertility; Mice; Paternal Age; Reproduction

Research Summary

Germ cells (sperm, eggs, and their developmental precursors) carry the genome from one generation to the next. The germ cell nucleus therefore carries all the information that will guide the development of the next generation, and that will subsequently be passed to future generations to ensure the survival of the species. How the physical genome is handled within the germ cells thus 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.

We have previously shown that epigenetic poising, a chromatin state characterized by the simultaneous presence of both activating and repressive histone marks and strongly associated with pluripotent stem cells, 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 amniote germ line, but evolves at specific locations in individual lineages in conjunction with 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, as well as examining additional aspects of germ cell genome regulation. See the lab website for more information about current projects.

Selected Publications

See list of PubMed publications

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Coauthors

Matthew Simon

Contact Info

Bluma Lesch, MD, PhD
Mailing Address
333 Cedar Street
SHM I-141A

New Haven, CT 06510

Lab website