Kyle E. Orwig, Ph.D.

Associate Professor of Obstetrics, Gynecology, and Reproductive Sciences, and Molecular Genetics and Biochemistry, University of Pittsburgh
Faculty Member, Pittsburgh Development Center
Assistant Investigator, Magee-Womens Research Institute

Ph.D., Oregon State University, 1994

Postdoctoral Fellowship, University of Kansas Medical Center, 1994-1998

Research Interests

Dr. Orwig's research focuses on the biology of male germline stem cells using mouse and rat experimental models. A spermatogonial transplantation technique, originally developed in mice, provides access to stem cells in the male germline and has been used to investigate stem cell/niche interactions, germline development, male infertility, and transgenesis. Current research is designed to:

Characterize gene expression in mouse and rat spermatogonial stem cells to identify regulatory networks controlling self-renewal and differentiation. Common themes in stem cell biology will be revealed by comparative genetic analysis with stem cells in other tissues and species.

Optimize the spermatogonial stem cell transplantation technique in rats as a first step toward extending the technology to other species. Progress in this objective will enable the generation of transgenic rats by genetic modification and transplantation of spermatogonial stem cells and has implications for fertility restoration in humans and germline modification in other species.

Develop methods to maintain and expand spermatogonial stem cells in culture. An in vitro culture system will complement in vivo efforts to understand stem cell regulatory networks and facilitate germline manipulations.

Selected Publications

Hermann BP, Sukhwani M, Winkler F, Pascarella JN, Peters KA, Sheng Y, Valli H, Rodriguez M, Ezzelarab M, Dargo G, Peterson K, Masterson K, Ramsey C, Ward T, M. Lienesch M, Volk A, Cooper DK, Thomson AW, Kiss JE, Penedo MC, Schatten GP, Mitalipov S, Orwig KE. 2012. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. Cell Stem Cell 11(5):715-26.

Easley 4th CA, Phillips BT, McGuire MM, Barringer JM, Valli H, Hermann BP, Simerly CR, Rajkovic A, Miki T, Orwig KE, Schatten GP. Direct differentiation of human pluripotent stem cells into haploid spermatogenic cells. 2012. Cell Rep. 2(3):440-6.

Suzuki H, Ahn HW, Chu T, Bowden W, Gassei K, Orwig K, Rajkovic A. 2012. SOHLH1 and SOHLH2 coordinate spermatogonial differentiation. Dev Biol. 361(2):301-12.

Clark AT, Phillips BT, Orwig KE. 2011. Fruitful progress to fertility: male fertility in the test tube. Nat Med. 17(12):1564-5.

Hermann BP, Sukhwani M, Salati J, Sheng Y, Chu T, Orwig KE. 2011. Separating spermatogonia from cancer cells in contaminated prepubertal primate testis cell suspensions. Hum Reprod. 26(12):3222-31.

Hermann BP, Phillips BT, Orwig KE. 2011. The elusive spermatogonial stem cell marker? Biol Reprod. Aug;85(2):221-3.

Ochalski ME, Shuttleworth JJ, Chu T, Orwig KE. Thalidomide treatment attenuates chemotherapy-induced gonadal toxicity. 2011; Fertil Steril. 95:819.

Phillips BT, Gassei K, Orwig KE. Spermatogonial stem cell regulation and spermatogenesis. 2010; Phil Trans R Soc B 365: 1663-1678.

Hermann BP, Sukhwani M, Hansel MC, Orwig KE. Spermatogonial stem cells in higher primates: are there differences from those in rodents? 2010; Reproduction 139: 479–493; DOI: 10.1530/REP-09-0255.

Sheng Y, Lin CC, Yue J, Sukhwani M, Shuttleworth JJ, Chu T, Orwig KE. Generation and characterization of a Tet-On (rtTA-M2) transgenic rat. BMC Developmental Biology 2010;10:17.

Hermann BP, Sukhwani M, Simorangkir DR, Chu T, Plant TM, Orwig KE. . Dissection of the Male Germ Cell Lineage Identifies Putative Spermatoganial Stem Cells in Rhesus Macaques. Hum Reprod. 2009; 24(7): 1704-16.

Escamilla-Hernandez R, Little-Ihrig L, Orwig K, Yue J, Chandran U, Zeleznik AJ. Constitutively Active Protein Kinase A Qualitatively Mimics the Effects of Follicle-Stimulating Hormone on Granulosa Cell Differentiation. Mol Endocrinol. 2008; 22(8): 1842-52.

Orwig KE, Ryu BY, Master S, Phillips BT, Mack M, Avarbock MR, Brinster RL. Genes Involved in Post-transcriptional Regulation are Over Represented in Stem/progenitor Spermatogonia of Cryptorchid Mouse Testes. Stem Cells. 2008; 26(4):927-38.

Yue J, Sheng Y, Orwig KE. Identification of novel homologous microRNA genes in the rhesus macaque genome. BMC Genomics. 2008; 9(1): 8.

Hermann BP, Sukhwani M, Lin CC, Sheng Y, Tomko J, Rodriguez M, Shuttleworth JJ, McFarland D, Hobbs RM, Pandolfi PP, Schatten GP, Orwig KE. Characterization, Cryopreservation and Ablation of Spermatogonial Stem Cells In Adult Rhesus Macaques. Stem Cells. 2007; 25(9):2330-2338.

Navara CS, Mich-Basso JD, Redinger CJ, Ben-Yehudah A, Jacoby E, Kovkarova-Naumovski E, Sukhwani M, Orwig K, Kaminski N, Castro CA, Simerly CR, Schatten G. Pedigreed Primate Embryonic Stem Cells, Express Homogeneous Familial Gene Profiles. Stem Cells. 2007; 25(11):2695-704.

Ryu BY, Orwig KE, Oatley, JM, Lin CC, Chang LJ, Avarbock MR, Brinster R. Efficient Generation of Transgenic Rats Through the Male Germline using Lentiviral Transduction and Transplantation of Spermatogonial Stem Cells. J Androl, 2007; 28(2):353-60.

Ryu BY, Orwig KE, Oatley, JM, Avarbock MR, Brinster RL. Effects of Aging and Niche Microenvironment on Spermatogonial Stem Cell Self-Renewal. Stem Cells, 2006; 26(6):1505-1511.

Orwig KE, Schlatt S. Cryopreservation and Transplantation of Spermatogonia and Testicular Tissue for Preservation of Male Fertility. J Natl Cancer Inst Monogr, 2005; 34:51-56.

Buageaw A, Sukhwani M, Ben-Yehudah A, Ehmcke J, Rawe VY, Pholpramool C, Orwig KE, Schlatt S. GDNF Family Receptor alpha1 Phenotype of Spermatogonial Stem Cells in Immature Mouse Testes. Biol. Reprod, 2005; 73(5):1011-1016.

Costoya JA, Hobbs RM, Barna M, Cattoretti G, Manova K, Sukhwani M, Orwig KE, Wolgemuth DJ, Pandolfi PP. Essential role of Plzf in Maintenance of Spermatogonial Stem Cells. Nature Genetics, 2004; 36:653-659.

Ryu BY, Orwig KE, Kubota H, Avarbock MR, Brinster RL. Phenotypic and functional characteristics of spermatogonial stem cells in rats. Developmental Biology, 2004; 274:158-170.

Complete Publication Listing

Professional Affiliations

International Society for Stem Cell Research
Society for the Study of Reproduction
American Society of Andrology
Editorial Board, Journal of Endocrinology
ZRG1 GTIE Study Section, NIH

Related Sites

The Orwig Laboratory

MWRI Fertility Preservation Program