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. In the mouse, prospermatogonia proliferate for a short period following sex determination in the fetal testis, and then become quiescent from approximately embryonic day (E)14.5 until postnatal day (P)1-2. Then, in response to an undefined signal(s), they move from a central position to the periphery of the testis cords and resume mitosis as spermatogonia. Completion of both tasks is required for their continued survival. Spermatogonia are then flanked by Sertoli cells within the cord and myoid cells outside the cord, and respond to paracrine signals from these somatic cells to either become spermatogonial stem cells (SSCs) or proliferate and differentiate in response to retinoic acid (RA) to ultimately enter meiosis. This self-renewal vs. differentiation spermatogonial fate decision is 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 minimal 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 – defining the requisite molecular signaling pathways downstream of RA, 2 – determining the role of RA in translational regulation during spermatogonial differentiation, and 3 – using a knockout approach to clarify the role of the reproductive homeobox gene 13 (RHOX13) in spermatogonial development and male fertility.
Geyer, C.B., R. Saba, Y. Kato, A.J. Anderson, V.K. Chappell, Y. Saga, and E.M. Eddy. 2012. Rhox13 is translated in premeiotic germ cells in male and female mice and translation is regulated by NANOS2 in the male. Biol. Reprod. 86: 127.
Overcash, R.F., V.A. Chappell, T. Green, C.B. Geyer, A.S. Asch, and M.J. Ruiz-Echevarria. 2013. Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α). PLoS One 8: e55257.
Niedenberger, B.A., V.K. Chappell, E.P. Kaye, R.H. Renegar, and C.B. Geyer. 2013. Nuclear localization of the actin binding protein Palladin in Sertoli cells. Mol. Reprod. Dev. 80: 403-413.
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.
"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.
Location ECHI 4400
|Kenneth (Trey) Cook||Undergraduate Studentfirstname.lastname@example.org|
|Oleksandr (Sasha) Kirsanov||Graduate Studentemail@example.com|
|Bryan Niedenberger||Research Technicianfirstname.lastname@example.org|
|Nicholas Serra||Graduate Studentemail@example.com|
|Ellen Velte||Graduate Studentfirstname.lastname@example.org|
|Jonathan Busada, Ph.D.||Postdoctoral Research Fellow||Signal Transduction Laboratory, National Institute of Environmental Health Science, Research Triangle Park, NC|