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Gunapala Shetty

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Experimental Radiation Oncology, Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

Cancer treatment using cytotoxic agents often produces prolonged azoospermia (absence of sperm in the semen) and infertility. To minimize the sterilizing effects of cytotoxic agents, we are investigating the use of hormones to enhance recovery of spermatogenesis after cytotoxic therapy.  We have discovered that the cytotoxic agents inactivate the differentiation of the stem cells by damaging the testicular somatic cells. We have made a very exciting discovery that testosterone, the hormone that is usually responsible for the stimulation of production of sperm in the normal male, can inhibit the initial stages of spermatogenesis in these pathological situations.  We are currently elucidating the mechanisms, using different hormone treatments, in vitro culultre, transplantation of specific testis cells between animals, and modeling these effects in mutant mice having a similar inhibition of differentiation of spermatogonia. We also have plans to test the feasibility of restoration of male fertility in cytotoxicant-treated non-human primate models by germ cell transplantation in combination with hormone suppression.Clinical applications of this research include restoration of fertility after radiation or chemotherapy for cancer (possibly with spermatogonial transplantation) and also in men with idiopathic infertility caused due to a block in the early differentiation of testicular stem cells.

Education & Training

Degree-Granting Education

1993 University of Mysore, Mysore, India, PHD, Reproductive Biology
1980 University of Mysore, Mysore, India, MS, Zoology
1978 University of Mysore, Mysore, India, BS, Chemistry/Botany/Zoology

Postgraduate Training

9/1997-10/2002 Postdoctoral Fellowship, The University of Texas MD Anderson Cancer Center, Houston, TX, Marvin L. Meistrich
3/1993-7/1997 Research Associate, Indian Institute of Science, Bangalore, India, Dr. N. R. Moudgal

Experience/Service

Academic Appointments

Instructor, Experimental Radiation Oncology, Division of Radiation Oncology, UT M. D. Anderson Cancer Center, Houston, Houston, TX, 11/2002-9/2006
Post Doc, Department of Radiation Oncology - Research, Division of Radiation Oncology, UT M. D. Anderson Cancer Center, Houston, Houston, TX, 1/1997-1/2002
Research Associate, Center for Reproductive Biology and Molecular Endocrinology, Indian Institute of Science, Bangalore, India, 1/1993-1/1997
Senior Research Assistant, Center for Reproductive Biology and Molecular Endocrinology, Indian Institute of Science, Bangalore, India, 1/1992-1/1993
Lecturer, Department of Zoology, University of Mysore, Mysore, India, 1/1989-1/1992

Honors and Awards

2002 H. Rodney Withers Lecture Award, RADONC, U. T. M. D. Anderson Cancer Center
1984-1987 Senior Research Fellowship, Council of Scientific and Industrial Research
1981-1984 Junior Research Fellowship, University Grants Commission

Selected Publications

Peer-Reviewed Original Research Articles
1. Zhou W, Bolden-Tiller OU, Shetty G, Shao SH, Weng CC, Pakarinen P, Liu Z, Stivers DN, Meistrich ML. Changes in Gene Expression in Somatic Cells of Rat Testes Resulting from Hormonal Modulation and Radiation-Induced Germ Cell Depletion. Biol Reprod 82(1):54-65, 1/2010. e-Pub 8/14/2009. PMCID: PMC2802113.
2. Dakhova O, O'Day D, Kinet N, Yucer N, Wiese M, Shetty G, Ducy P. Dickkopf-like1 regulates postpubertal spermatocyte apoptosis and testosterone production. Endocrinology 150(1):404-12, 2009. PMID: 18818293.
3. Porter KL, Shetty G, Shuttlesworth GA, Weng CC, Huhtaniemi I, Pakarinen P, Meistrich ML. Estrogen enhances recovery from radiation-induced spermatogonial arrest in rat testes. J Androl 30(4):440-51, Jul-Aug, 2009. PMID: 19136390.
4. Zhang Z, Shao S, Shetty G, Meistrich ML. Donor Sertoli cells transplanted into irradiated rat testes stimulate partial recovery of endogenous spermatogenesis. Reproduction 137(3):497-508, 2008. PMID: 19036951.
5. Shetty G, Shao SH, Weng CC. p53-dependent apoptosis in the inhibition of spermatogonial differentiation in juvenile spermatogonial depletion (Utp14bjsd) mice. Endocrinology 149(6):2773-81, 2008. PMID: 18356279.
6. Bolden-Tiller OU, Chiarini-Garcia H, Poirier C, Alves-Freitas D, Weng CC, Shetty G, Meistrich ML. Genetic factors contributing to defective spermatogonial differentiation in juvenile spermatogonial depletion (Utp14bjsd) mice. Biol Reprod 77(2):237-46, 2007. PMID: 17475932.
7. Shetty G, Weng CC, Meachem SJ, Bolden-Tiller OU, Zhang Z, Pakarinen P, Huhtaniemi I, Meistrich ML. Both testosterone and follicle-stimulating hormone independently inhibit spermatogonial differentiation in irradiated rats. Endocrinology 147(1):472-82, 2006. PMID: 16210366.
8. Shetty G, Weng CC, Porter KL, Zhang Z, Pakarinen P, Kumar TR, Meistrich ML. Spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice with androgen receptor or follicle-stimulating hormone mutations. Endocrinology 147(7):3563-70, 2006. PMID: 16627582.
9. Porter KL, Shetty G, Meistrich ML. Testicular edema is associated with spermatogonial arrest in irradiated rats. Endocrinology 147(3):1297-305, 2006. PMID: 16306082.
10. Boekelheide K, Schoenfeld HA, Hall SJ, Weng CC, Shetty G, Leith J, Harper J, Sigman M, Hess DL, Meistrich ML. Gonadotropin-releasing hormone antagonist (Cetrorelix) therapy fails to protect nonhuman primates (Macaca arctoides) from radiation-induced spermatogenic failure. J Androl 26(2):222-34, 2005. PMID: 15713828.
11. Shetty G, Weng CC. Cryptorchidism rescues spermatogonial differentiation in juvenile spermatogonial depletion (jsd) mice. Endocrinology 145(1):126-33, 2004. PMID: 14500567.
12. Shetty G, Weng CC, Bolden-Tiller OU, Huhtaniemi I, Handelsman DJ, Meistrich ML. Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats. Endocrinology 145(10):4461-9, 2004. PMID: 15205377.

Invited Articles
1. Meistrich M, Shetty G. Hormonal Suppression for Fertility Preservation in Males and Females. Reproduction, 2008. PMID: 18515310.
2. Shetty G, Meistrich ML. The missing niche for spermatogonial stem cells: do blood vessels point the way? Cell Stem Cell 1(4):361-3, 2007. PMID: 18371373.

Grant & Contract Support

Title: Optimizing Spermatogonial transplantation for fertility preservation
Funding Source: NIH/NICHD
Role: Principal Investigator
Duration: 9/3/2009 - 8/31/2011
 
Title: Reversal of Spermatogonial Arrest in Mice
Funding Source: NIH/NICHD
Role: Co-Investigator
Principal Investigator: Meistrich
Duration: 12/1/2007 - 11/30/2013
 
Title: Activation of Spermatogenic Recovery after Toxic Insult
Funding Source: NIH/NIEHS
Role: Co-Investigator
Principal Investigator: Meistrich
Duration: 6/1/2007 - 3/31/2012

Last updated: 8/24/2010