Lab Interests
Molecular Mechanisms and Pathways Required for Proper Germ Cell and Embryo Development
Germ Cell Comparative Biology
The mammalian testis is a complex tissue made up of many diverse cell types, including mitotic, meiotic, and morphologically maturing germ cells, as well as somatic cells involved in support, immune regulation, and steroidogenesis. By conducting comparative analyses of testicular cell populations, their regulation, and interaction in different species, we hope to better understand the evolution of sperm differentiation and entry into meiosis.
Dissecting Germ Cell-Soma Communication
The process of spermatogenesis relies on an intricate dialogue between germ cells and their adjoining somatic neighbors for proper differentiation. Through the use of single cell genomics and spatial mapping we hope to uncover molecular genetics pathways and cross-talk between germ cells and their supporting somatic cells in order to drive this process in vitro or in a surrogate system.
Making Somatic Cells of the Testis
The multiple somatic cell types in the mammalian testis influence neighboring somatic cells and are essential for normal germ cell development, but details about somatic cell origin, specification regulatory programs, sub-types, and inter-cellular communications remain poorly understood. By using genetic lineage tracing approaches and single cell technologies we hope to define molecular genetic programs and recapitulate these processes in vitro.
Chromatin Regulation of Meiotic DSB Repair
Meiotic recombination is a highly conserved process characterized by the induction and subsequent repair of 200-300 DNA double-strand breaks (DSBs) in embryonic oocytes. A select subset of these DSBs are repaired as crossovers: a genetic tethering of homologous chromosomes that form the structural foundation of heredity. This physical linkage is essential for fertility and can remain intact for months in mice and decades in humans. While many factors important for crossover formation, and therefore fertility, have been identified, many questions remain about the distinct molecular events that allow their formation.
Sex Specific Centromere Maintenance
Contribution of the Male Germline Chromatin to Development and Disease
Epigenetic Inheritance
Unlike somatic cells, the sperm genome is packaged in histones and protamines. Whether this unique chromatin landscape is a remnant of gametogenesis or instructive for development is unknown. We have developed novel genetic strategies to explore the role and significance of histones in spermatogenesis and early embryonic development.
Protamine Protein Structure-Function
Protamines are small basic nuclear proteins essential for tight compaction of paternal chromatin into the hydrodynamic sperm nucleus. Proper deposition and removal of protamines is critical to normal fertility. The evolutionary significance of protamine protein incorporation remains elusive. To revisit the role of protamine proteins, we are utilizing novel biochemical and genomic techniques to explore the structure and function of these proteins across species.
