Society for the Study of Reproduction New Investigator Award 2017
office: ECHI 4112
B.S., Virginia Polytechnic Institute and State University
Ph.D., The University of Texas Health Science Center at San Antonio
Postdoctoral Fellow, National Institute of Environmental Health Sciences
My laboratory uses mouse spermatogenesis as a model system to investigate mechanisms involved in regulating cellular differentiation. Spermatogenesis begins in the neonatal mouse testis with the segregation of prospermatogonia into distinct undifferentiated and differentiating populations. 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). This initial fate decision is critical, as imbalances cause spermatogenic defects that can lead to human testicular cancer or infertility. 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.
Chappell, V.A., J.T. Busada, B.D. Keiper, and C.B. Geyer. 2013. Translational activation of developmental mRNAs during neonatal testis development. Biol. Reprod. 89: 61.
Busada, J.T., E.P Kaye, R.H. Renegar, and C.B. Geyer. 2014. Retinoic acid induces multiple hallmarks of the prospermatogonia-to-spermatogonia transition in the neonatal mouse. Biol. Reprod. 90: 64.
Niedenberger, B.A., V.A. Chappell, C.A. Otey, and C.B. Geyer. 2014. Actin dynamics regulate subcellular localization of the F-actin binding protein PALLD in mouse Sertoli cells. Reproduction 148: 333-341.
Busada, J.T., V.A. Chappell, B.A. Niedenberger, E.P. Kaye, B.D. Keiper, C.A. Hogarth, and C.B. Geyer. 2014. Retinoic acid regulates Kit translation during spermatogonial differentiation in the mouse. Dev. Biol. 397: 140-149.
Hermann, B.P., K.N. Mutoji, E.K. Velte, D. Ko, J.M. Oatle, C.B. Geyer, and J.R. McCarrey. 2015. Transcriptional and translational heterogeneity among neonatal mouse spermatogonia. Biol. Reprod. 92: 54.
Niedenberger, B.A., J.T. Busada, and C.B. Geyer. 2015. Marker expression reveals heterogeneity of spermatogonia in the neonatal mouse testis. Reproduction 149: 329-338.
Busada, J.T., B.A. Niedenberger, E.K. Velte, B.D. Keiper, and C.B. Geyer. 2015. Mammalian target of rapamycin complex 1 (mTORC1) is required for mouse spermatogonial differentiation in vivo. Dev. Biol. 407: 90-102.
Busada, J.T. and C.B. Geyer. 2015. The role of retinoic acid (RA) in spermatogonial differentiation. Biol. Reprod. 94: 10.
Busada, J.T., E.K. Velte, N.Serra, K. Cook, B.A. Niedenberger, W.D. Willis, E.H. Goulding, E.M. Eddy, and C.B. Geyer. 2016. Rhox13 is required for a quantitatively normal first wave of spermatogenesis in mice. Reproduction 152: 379-88.
Mutoji, K., A. Singh, T. Nguyen, H. Gildersleeve, A.V. Kaucher, M.J. Oatley, J.M. Oatley, E.K. Velte, C.B. Geyer, K. Cheng, J.R. McCarrey, and B.P Hermann. 2016. TSPAN8 expression distinguishes spermatogonial stem cells in the prepubertal mouse testis. Biol. Reprod. 95(6): 117.
"Analysis of a Translation Repression Program during Neonatal Male Germ Cell Development" (NIH R15 2R15HD072552-02A1); Christopher Geyer, Principal Investigator; National Institute of Child Health and Human Development; 11/23/2015-10/31/2018.
"The Role of Retinoid Exposure in Specification of the Foundational SSC Pool" (NIH R01 1R01HD090083-01A1); Christopher Geyer, Principal Investigator; National Institute of Child Health and Human Development; anticipated start date 5/01/2017.
Location ECHI 4400
|Kenneth (Trey) Cook||Undergraduate Studentemail@example.com|
|Oleksandr (Sasha) Kirsanov||Graduate Studentfirstname.lastname@example.org|
|Bryan Niedenberger||Research Technicianemail@example.com|
|Nicholas Serra||Graduate Studentfirstname.lastname@example.org|
|Ellen Velte||Graduate Studentemail@example.com|
|Jonathan Busada, Ph.D.||Postdoctoral Research Fellow||Signal Transduction Laboratory, National Institute of Environmental Health Science, Research Triangle Park, NC|