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Ralph Brinster
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Professor of Physiology, School of Veterinary Medicine, University of Pennsylvania.
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Professor of Physiology, Graduate School of Arts & Sciences and Graduate Faculty, University of Pennsylvania
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Richard King Mellon Professor of Reproductive Physiology, School of Veterinary Medicine and Graduate School, University of Pennsylvania
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Contact information
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100E School of Veterinary Medicine, University of Pennsylvania
35 3800 Spruce Street
Philadelphia, PA 19104
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35 3800 Spruce Street
Philadelphia, PA 19104
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Office: (215) 898-8805
34 Fax: (215) 898-0667
34 Lab: (215) 898-8805
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34 Fax: (215) 898-0667
34 Lab: (215) 898-8805
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Email:
brinster@vet.upenn.edu
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brinster@vet.upenn.edu
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Publications
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Links
d7 Search PubMed for articles
aa International Journal of Developmental Biology: Interview with R. L. Brinster
9e School of Veterinary Medicine Faculty Profile
95 Brinster Symposium - 2012
a1 Profile in Penn Vet Research newsletter
d8 National Medal of Science - White House Press Release 2011
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d7 Search PubMed for articles
aa International Journal of Developmental Biology: Interview with R. L. Brinster
9e School of Veterinary Medicine Faculty Profile
95 Brinster Symposium - 2012
a1 Profile in Penn Vet Research newsletter
d8 National Medal of Science - White House Press Release 2011
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Education:
21 9 B.S. 22 (School of Agriculture) c
2c Rutgers University, 1953.
21 b V.M.D. 2a (School of Veterinary Medicine) c
33 University of Pennsylvania, 1960.
21 9 Ph.D 2e (Graduate School of Arts & Science) c
33 University of Pennsylvania, 1964.
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Permanent link21 9 B.S. 22 (School of Agriculture) c
2c Rutgers University, 1953.
21 b V.M.D. 2a (School of Veterinary Medicine) c
33 University of Pennsylvania, 1960.
21 9 Ph.D 2e (Graduate School of Arts & Science) c
33 University of Pennsylvania, 1964.
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745 The research in Dr. Brinster’s laboratory focuses on the biology of the spermatogonial stem cell (SSC), which is responsible for the continuity of spermatogenesis in the adult male. A spermatogonial transplantation technique has been developed that provides a functional assay of stem cell activity, thereby enabling for the first time an analysis of this unique and valuable stem cell population. Using the transplantation assay the surface antigenic profile of the SSC has been established for several species, and this information allows highly enriched populations of stem cells to be obtained. These enriched SSCs from mouse and rat can now be cultured, and their number increased for long periods. Techniques to extend the culture system to farm animals and primates are under investigation. Additionally, genes are being introduced into the SSC as a technique to modify the germline of animals. Development of culture and gene modification methods for rodent SSCs will lay the foundation for similar approaches in larger animals, particularly farm animals. The culture and enrichment strategies also are being used to study gene activity in stem cells and differentiating daughter cells arising from the stem cells. Using similar methods, signaling pathways active in the fate decision determining stem cell self-renewal or differentiation are under investigation. Since the SSC is the only adult stem cell for which there exists a long-term in vitro culture system and a quantitative functional transplantation assay, it provides a powerful model to understand stem cell function in all adult stem cell systems. In addition, the SSC is the only stem cell in the adult that continually replicates and transmits genes to the next generation. Perhaps most important, it is the vehicle for species continuity and evolutionary adaptation.
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Description of Research Expertise
23 Research Interests745 The research in Dr. Brinster’s laboratory focuses on the biology of the spermatogonial stem cell (SSC), which is responsible for the continuity of spermatogenesis in the adult male. A spermatogonial transplantation technique has been developed that provides a functional assay of stem cell activity, thereby enabling for the first time an analysis of this unique and valuable stem cell population. Using the transplantation assay the surface antigenic profile of the SSC has been established for several species, and this information allows highly enriched populations of stem cells to be obtained. These enriched SSCs from mouse and rat can now be cultured, and their number increased for long periods. Techniques to extend the culture system to farm animals and primates are under investigation. Additionally, genes are being introduced into the SSC as a technique to modify the germline of animals. Development of culture and gene modification methods for rodent SSCs will lay the foundation for similar approaches in larger animals, particularly farm animals. The culture and enrichment strategies also are being used to study gene activity in stem cells and differentiating daughter cells arising from the stem cells. Using similar methods, signaling pathways active in the fate decision determining stem cell self-renewal or differentiation are under investigation. Since the SSC is the only adult stem cell for which there exists a long-term in vitro culture system and a quantitative functional transplantation assay, it provides a powerful model to understand stem cell function in all adult stem cell systems. In addition, the SSC is the only stem cell in the adult that continually replicates and transmits genes to the next generation. Perhaps most important, it is the vehicle for species continuity and evolutionary adaptation.
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147 Ginsberg, J. P., Brinster, R. L.: Transplantation of cryopreserved spermatogonia. Principles & Practice of Fertility Preservation. Jacques Donnez and S. Samuel Kim (eds.). Cambridge University Press, Cambridge, UK, Chapter 15, Section IV : 199-208, 2011.
146 Oatley, J. M., Oatley, M. J., Avarbock, M. R., Tobias, J. W., Brinster, R. L.: Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 136(7): 1191-1199, Apr 2009 Notes: DOI: 10.1242/dev.032243.
1cb Wu, X, Schmidt, J.A., Avarbock, M.R., Tobias, J. W., Carlson, C. A., Kolon, T. F., Ginsberg, J. P., Brinster, R. L.: Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proceedings of the National Academy of Sciences of the United States of America 106: 21672-21677, 2009 Notes: DOI: 10.1073/pnas.0913432106.
16a Oatley, J. M., Brinster, R. L.: Regulation of spermatogonial stem cell self-renewal in mammals. Annu. Rev. Cell Dev. Biol. Randy Schekman, Larry Goldstein and Janet Rossant. (eds.). Annual Reviews, Palo Alto, CA, 24: 263-286, 2008 Notes: DOI: 110.1146/annurev.cellbio.24. 110707.175355.
ac Brinster, R.L.: Male germline stem cells: from mice to men. Science 316(5823): 404-5, Apr 20 2007.
10b Kubota, H. Avarbock, M.R. Brinster, R.L.: Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc. Natl. Acad. Sci. USA 101(47): 16489-94, Nov 23 2004.
b6 Brinster, R.L.: Germline stem cell transplantation and transgenesis. Science 296(5576): 2174-6, Jun 21 2002.
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Selected Publications
c7 Oatley, J.M. Brinster, R.L.: The germline stem cell niche unit in mammalian testes. Physiol. Rev. 92(2): 577-95, April 2012.147 Ginsberg, J. P., Brinster, R. L.: Transplantation of cryopreserved spermatogonia. Principles & Practice of Fertility Preservation. Jacques Donnez and S. Samuel Kim (eds.). Cambridge University Press, Cambridge, UK, Chapter 15, Section IV : 199-208, 2011.
146 Oatley, J. M., Oatley, M. J., Avarbock, M. R., Tobias, J. W., Brinster, R. L.: Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 136(7): 1191-1199, Apr 2009 Notes: DOI: 10.1242/dev.032243.
1cb Wu, X, Schmidt, J.A., Avarbock, M.R., Tobias, J. W., Carlson, C. A., Kolon, T. F., Ginsberg, J. P., Brinster, R. L.: Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proceedings of the National Academy of Sciences of the United States of America 106: 21672-21677, 2009 Notes: DOI: 10.1073/pnas.0913432106.
16a Oatley, J. M., Brinster, R. L.: Regulation of spermatogonial stem cell self-renewal in mammals. Annu. Rev. Cell Dev. Biol. Randy Schekman, Larry Goldstein and Janet Rossant. (eds.). Annual Reviews, Palo Alto, CA, 24: 263-286, 2008 Notes: DOI: 110.1146/annurev.cellbio.24. 110707.175355.
ac Brinster, R.L.: Male germline stem cells: from mice to men. Science 316(5823): 404-5, Apr 20 2007.
10b Kubota, H. Avarbock, M.R. Brinster, R.L.: Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc. Natl. Acad. Sci. USA 101(47): 16489-94, Nov 23 2004.
b6 Brinster, R.L.: Germline stem cell transplantation and transgenesis. Science 296(5576): 2174-6, Jun 21 2002.
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