The Hammes laboratory studies how steroidogenesis and steroid signaling in the ovary regulate ovarian development and function.

First, they use frog and mouse models of steroid-triggered oocyte maturation (meiotic resumption) to study transcription-independent, or nongenomic, steroid signaling. The laboratory has made many important discoveries regarding the roles of androgens, androgen receptors, and G proteins in regulating the maturation process. They are interested in studying how this nongenomic androgen signaling might affect ovarian development and function in diseases of androgen excess, such as polycystic ovarian syndrome (PCOS).

Second, the laboratory uses mouse models to characterize the intracellular signaling pathways triggered by gonadotropins during steroidogenesis, focusing on potential signaling molecules that can be specifically targeted to reduce ovarian androgen production in PCOS.

Third, the laboratory is interested in understanding ovarian follicle development, and is studying a novel GATA-like protein that is expressed in granulosa cells, may regulate steroidogenesis, and is essential for normal embryonic follicle development and germ cell survival.

Finally, the laboratory has recently begun to study how transcription-independent androgen signaling can regulate steroid-sensitive tumors, such as prostate cancer. This work involves characterization of the mechanisms regulating steroid-triggered MAPK signaling, focusing on potential therapeutic targets that can be translated into the clinic.

• Sen A, De Castro I, Defranco DB, Deng FM, Melamed J, Kapur P, Raj GV, Rossi R, Hammes SR. Paxillin mediates extranuclear and intranuclear signaling in prostate cancer proliferation. J Clin Invest. 2012 Jul 2; 122(7):2469-81.
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• Grubisha MJ, Cifuentes ME, Hammes SR, Defranco DB. A Local Paracrine and Endocrine Network Involving TGFß, Cox-2, ROS, and Estrogen Receptor ß Influences Reactive Stromal Cell Regulation of Prostate Cancer Cell Motility. Mol Endocrinol. 2012 Jun; 26(6):940-54.
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• Yang L, Ravindranathan P, Ramanan M, Kapur P, Hammes SR, Hsieh JT, Raj GV. Central Role for PELP1 in Nonandrogenic Activation of the Androgen Receptor in Prostate Cancer. Mol Endocrinol. 2012 Apr; 26(4):550-61.
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• Hammes SR, Levin ER. Minireview: recent advances in extranuclear steroid receptor actions. Endocrinology. 2011 Dec; 152(12):4489-95.
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• Hammes SR, Kelly MJ, Slingerland JM. The physiology of integrated nuclear and extranuclear steroid signaling: introductory comments. Steroids. 2011 Aug; 76(9):821.
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• Carbajal L, Biswas A, Niswander LM, Prizant H, Hammes SR. GPCR/EGFR cross talk is conserved in gonadal and adrenal steroidogenesis but is uniquely regulated by matrix metalloproteinases 2 and 9 in the ovary. Mol Endocrinol. 2011 Jun; 25(6):1055-65.
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• Sen A, Prizant H, Hammes SR. Understanding extranuclear (nongenomic) androgen signaling: what a frog oocyte can tell us about human biology. Steroids. 2011 Aug; 76(9):822-8.
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• Strauss TJ, Castrillon DH, Hammes SR. GATA-like protein-1 (GLP-1) is required for normal germ cell development during embryonic oogenesis. Reproduction. 2011 Feb; 141(2):173-81.
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• Sen A, O'Malley K, Wang Z, Raj GV, Defranco DB, Hammes SR. Paxillin regulates androgen- and epidermal growth factor-induced MAPK signaling and cell proliferation in prostate cancer cells. J Biol Chem. 2010 Sep 10; 285(37):28787-95.
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• Sen A, Hammes SR. Just when you thought it was safe to go into the membrane: the growing complexities of extra-nuclear progesterone signaling. Breast Cancer Res. 2010; 12(3):109.
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• Sen A, Hammes SR. Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function. Mol Endocrinol. 2010 Jul; 24(7):1393-403.
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• Grasfeder LL, Gaillard S, Hammes SR, Ilkayeva O, Newgard CB, Hochberg RB, Dwyer MA, Chang CY, McDonnell DP. Fasting-induced hepatic production of DHEA is regulated by PGC-1alpha, ERRalpha, and HNF4alpha. Mol Endocrinol. 2009 Aug; 23(8):1171-82.
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• Ghayee HK, Havekes B, Corssmit EP, Eisenhofer G, Hammes SR, Ahmad Z, Tessnow A, Lazúrová I, Adams KT, Fojo AT, Pacak K, Auchus RJ. Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior. Endocr Relat Cancer. 2009 Mar; 16(1):291-9.
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• Carbajal L, Deng J, Dressing GE, Hagan CR, Lange CA, Hammes SR. Meeting review: Extra-nuclear steroid receptors-Integration with multiple signaling pathways. Steroids. 2009 Jul; 74(7):551-4.
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• Deng J, Carbajal L, Evaul K, Rasar M, Jamnongjit M, Hammes SR. Nongenomic steroid-triggered oocyte maturation: of mice and frogs. Steroids. 2009 Jul; 74(7):595-601.
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• Evaul K, Hammes SR. Cross-talk between G protein-coupled and epidermal growth factor receptors regulates gonadotropin-mediated steroidogenesis in Leydig cells. J Biol Chem. 2008 Oct 10; 283(41):27525-33.
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• Deng J, Lang S, Wylie C, Hammes SR. The Xenopus laevis isoform of G protein-coupled receptor 3 (GPR3) is a constitutively active cell surface receptor that participates in maintaining meiotic arrest in X. laevis oocytes. Mol Endocrinol. 2008 Aug; 22(8):1853-65.
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• Hammes SR, Levin ER. Extranuclear steroid receptors: nature and actions. Endocr Rev. 2007 Dec; 28(7):726-41.
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• Lange CA, Gioeli D, Hammes SR, Marker PC. Integration of rapid signaling events with steroid hormone receptor action in breast and prostate cancer. Annu Rev Physiol. 2007; 69:171-99.
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• Gill A, Hammes SR. G beta gamma signaling reduces intracellular cAMP to promote meiotic progression in mouse oocytes. Steroids. 2007 Feb; 72(2):117-23.
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• Rasar M, DeFranco DB, Hammes SR. Paxillin regulates steroid-triggered meiotic resumption in oocytes by enhancing an all-or-none positive feedback kinase loop. J Biol Chem. 2006 Dec 22; 281(51):39455-64.
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• Evaul K, Jamnongjit M, Bhagavath B, Hammes SR. Testosterone and progesterone rapidly attenuate plasma membrane Gbetagamma-mediated signaling in Xenopus laevis oocytes by signaling through classical steroid receptors. Mol Endocrinol. 2007 Jan; 21(1):186-96.
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• VanLandingham JW, Cutler SM, Virmani S, Hoffman SW, Covey DF, Krishnan K, Hammes SR, Jamnongjit M, Stein DG. The enantiomer of progesterone acts as a molecular neuroprotectant after traumatic brain injury. Neuropharmacology. 2006 Nov; 51(6):1078-85.
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• Li S, Lu MM, Zhou D, Hammes SR, Morrisey EE. GLP-1: a novel zinc finger protein required in somatic cells of the gonad for germ cell development. Dev Biol. 2007 Jan 1; 301(1):106-16.
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• Jamnongjit M, Hammes SR. Ovarian steroids: the good, the bad, and the signals that raise them. Cell Cycle. 2006 Jun; 5(11):1178-83.
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• Rasar MA, Hammes SR. The physiology of the Xenopus laevis ovary. Methods Mol Biol. 2006; 322:17-30.
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• Jamnongjit M, Gill A, Hammes SR. Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation. Proc Natl Acad Sci U S A. 2005 Nov 8; 102(45):16257-62.
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• Jamnongjit M, Hammes SR. Oocyte maturation: the coming of age of a germ cell. Semin Reprod Med. 2005 Aug; 23(3):234-41.
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• Haas D, White SN, Lutz LB, Rasar M, Hammes SR. The modulator of nongenomic actions of the estrogen receptor (MNAR) regulates transcription-independent androgen receptor-mediated signaling: evidence that MNAR participates in G protein-regulated meiosis in Xenopus laevis oocytes. Mol Endocrinol. 2005 Aug; 19(8):2035-46.
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• White SN, Jamnongjit M, Gill A, Lutz LB, Hammes SR. Specific modulation of nongenomic androgen signaling in the ovary. Steroids. 2005 May-Jun; 70(5-7):352-60.
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• Yang WH, Hammes SR. Xenopus laevis CYP17 regulates androgen biosynthesis independent of the cofactor cytochrome b5. J Biol Chem. 2005 Mar 18; 280(11):10196-201.
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• Hammes SR. Steroids and oocyte maturation--a new look at an old story. Mol Endocrinol. 2004 Apr; 18(4):769-75.
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• Gill A, Jamnongjit M, Hammes SR. Androgens promote maturation and signaling in mouse oocytes independent of transcription: a release of inhibition model for mammalian oocyte meiosis. Mol Endocrinol. 2004 Jan; 18(1):97-104.
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• Han S, Xie W, Hammes SR, DeJong J. Expression of the germ cell-specific transcription factor ALF in Xenopus oocytes compensates for translational inactivation of the somatic factor TFIIA. J Biol Chem. 2003 Nov 14; 278(46):45586-93.
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• Lutz LB, Jamnongjit M, Yang WH, Jahani D, Gill A, Hammes SR. Selective modulation of genomic and nongenomic androgen responses by androgen receptor ligands. Mol Endocrinol. 2003 Jun; 17(6):1106-16.
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• Hammes SR. The further redefining of steroid-mediated signaling. Proc Natl Acad Sci U S A. 2003 Mar 4; 100(5):2168-70.
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• Yang WH, Lutz LB, Hammes SR. Xenopus laevis ovarian CYP17 is a highly potent enzyme expressed exclusively in oocytes. Evidence that oocytes play a critical role in Xenopus ovarian androgen production. J Biol Chem. 2003 Mar 14; 278(11):9552-9.
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• Thøgersen IB, Hammes SR, Rubenstein DS, Pizzo SV, Valnickova Z, Enghild JJ. New member of the trefoil factor family of proteins is an alpha-macroglobulin protease inhibitor. Biochim Biophys Acta. 2002 Jul 29; 1598(1-2):131-9.
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• Lutz LB, Cole LM, Gupta MK, Kwist KW, Auchus RJ, Hammes SR. Evidence that androgens are the primary steroids produced by Xenopus laevis ovaries and may signal through the classical androgen receptor to promote oocyte maturation. Proc Natl Acad Sci U S A. 2001 Nov 20; 98(24):13728-33.
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• Lutz LB, Kim B, Jahani D, Hammes SR. G protein beta gamma subunits inhibit nongenomic progesterone-induced signaling and maturation in Xenopus laevis oocytes. Evidence for a release of inhibition mechanism for cell cycle progression. J Biol Chem. 2000 Dec 29; 275(52):41512-20.
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• Hammes SR, Shapiro MJ, Coughlin SR. Shutoff and agonist-triggered internalization of protease-activated receptor 1 can be separated by mutation of putative phosphorylation sites in the cytoplasmic tail. Biochemistry. 1999 Jul 20; 38(29):9308-16.
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• Hammes SR, Coughlin SR. Protease-activated receptor-1 can mediate responses to SFLLRN in thrombin-desensitized cells: evidence for a novel mechanism for preventing or terminating signaling by PAR1's tethered ligand. Biochemistry. 1999 Feb 23; 38(8):2486-93.
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• Trejo J, Hammes SR, Coughlin SR. Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting. Proc Natl Acad Sci U S A. 1998 Nov 10; 95(23):13698-702.
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• Kahn ML, Hammes SR, Botka C, Coughlin SR. Gene and locus structure and chromosomal localization of the protease-activated receptor gene family. J Biol Chem. 1998 Sep 4; 273(36):23290-6.
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• Hsu DK, Hammes SR, Kuwabara I, Greene WC, Liu FT. Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the beta-galactoside-binding lectin, galectin-3. Am J Pathol. 1996 May; 148(5):1661-70.
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• Hammes SR, Greene WC. Multiple arginine residues within the basic domain of HTLV-I Rex are required for specific RNA binding and function. Virology. 1993 Mar; 193(1):41-9.
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• Fung MR, Scearce RM, Hoffman JA, Peffer NJ, Hammes SR, Hosking JB, Schmandt R, Kuziel WA, Haynes BF, Mills GB, et al. A tyrosine kinase physically associates with the beta-subunit of the human IL-2 receptor. J Immunol. 1991 Aug 15; 147(4):1253-60.
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• Hammes SR, Dixon EP, Malim MH, Cullen BR, Greene WC. Nef protein of human immunodeficiency virus type 1: evidence against its role as a transcriptional inhibitor. Proc Natl Acad Sci U S A. 1989 Dec; 86(23):9549-53.
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• Hammes S, Holowka D, Baird B. Proteolytic digestion of the beta and gamma subunits of the receptor for immunoglobulin E at the cytoplasmic face of the plasma membrane. J Recept Res. 1989; 9(3):235-58.
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• Estes K, Monfalcone LL, Hammes SR, Holowka D, Baird B. Membrane-bound IgE receptor complexes fused with rat basophilic leukemia cells mediate degranulation. J Cell Biol. 1987 Aug; 105(2):747-53.
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