Research & Funding
Research Projects
“Discovery consists of seeing what everybody has seen, and thinking what nobody has thought.”
Our laboratory uses mouse spermatogenesis as a model system to investigate mechanisms that regulate cellular differentiation. Spermatogenesis begins in the neonatal mouse testis with the segregation of precursor prospermatogonia into distinct undifferentiated and differentiating populations of spermatogonia. A proportion of undifferentiated spermatogonia retain stem cell potential (as foundational spermatogonial stem cells, or SSCs), and the remainder becomes progenitor spermatogonia that proliferate and differentiate in response to retinoic acid (RA). It is currently unknown how mammalian spermatogonial fate decisions are regulated; however, they are critical for maintaining tissue homeostasis, as imbalances cause spermatogenesis defects that can lead to human testicular cancer or infertility. A great deal of effort has been exerted to understand how the SSC population is maintained. In contrast, little is known about the essential program of differentiation initiated by RA that precedes meiosis, and the pathways and proteins involved are poorly defined. A primary reason for this gap in knowledge is there are few reported changes in steady state mRNA levels during differentiation, preventing identification of the full complement of involved gene products to inform focused studies.
To better understand neonatal germ cell differentiation at the onset of spermatogenesis, we are currently: 1 – using transgenic and knockout mice to define the requisite molecular signaling pathways downstream of RA, 2 – determining the role of RA in translational regulation during spermatogonial differentiation, and 3 – defining how RA responsiveness regulates spermatogonial fate and the formation of the foundational SSC pool at the beginning of spermatogenesis.
Current funding
R61 grant from the NICHD (with Drs. Brian Hermann and Yaxia Yuan as co-PIs) from 2024-2026 entitled “Development of small molecule inhibitors of RBM46 as novel male contraceptives” (R61HD114223).
R01 grant from the NICHD (with Dr. Darrell Neufer as co-PI) from 2023-2027 entitled “Selecting sperm with distinct metabolic phenotypes to increase ART efficiency” (R01HD110170).
R21 grant from the NICHD (with Dr. Karen Schindler as co-Investigator) from 2022-2025 (in NCE) entitled “Challenging the role of retinoic acid in meiotic initiation” (R21HD105963).
