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Pathology

Houston, Texas

Department of Pathology
Pathology
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Faculty

Martin M. Matzuk , M.D.,Ph. D.The Stuart A. Wallace Chair, Department of Pathology, Department of Molecular and Cellular Biology, Department of Molecular and Human Genetics, Co-Director, Medical Scientist Training

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Education

  • M.D., Ph.D., Washington University School of Medicine

Area of Interest

  • Reproductive and embryonic development are complex processes which require the coordinated interaction of multiple proteins. The overall research goals of my laboratory are directed at elucidating the critical proteins involved in both normal and abnormal reproductive development. These studies are focusing on both extragonadal regulators such as luteinizing hormone and follicle stimulating hormone and intragonadal regulators such as the inhibins, activins, and growth/differentiation factor 9 (GDF-9). These latter proteins are members of the large TGF-b superfamily of secreted growth factors and appear to play important roles in multiple tissues as endocrine, paracrine, and autocrine mediators during both embryonic and adult development

  • To characterize the roles of these proteins in mammalian reproduction and development, we have taken a systematic approach to generate standard transgenic mice as well as "knock-out" mice deficient in a number of these genes using gene targeting and embryonic stem (ES) cell technology. Analysis of the mice generated in these "gain of function" and "loss of function" experiments have revealed the critical roles of several of these proteins in mammalian reproduction, development, and oncogenesis. Initial studies to generate mice deficient in the inhibins have already demonstrated the power of this approach revealing that inhibin is a novel tumor suppressor with specificity for the gonads and the adrenal gland. Similarly, mice deficient in GDF-9 have defined it as the first oocyte-derived growth factor required for somatic cell function in vivo. Current studies using these transgenic mice as in vivo tools will enable us to more fully understand the relationship of these proteins in reproduction, development, and oncogenesis

Honors and Awards

  • Experimental Pathologist-in-Training Award, American Society for Investigative Pathology, 1993

  • The Michael E. DeBakey, M.D., Excellence in Research Award, Baylor College of Medicine, 1995

  • The Richard E. Weitzman Memorial Award, The Endocrine Society, 1996

  • The HypoCCS Award, Eli Lilly, 1999

  • O'Neal/Spjut Award, Baylor College of Medicine, 2001

  • NIH MERIT Award, R01HD33438, May 1, 2001

  • Pfizer Outstanding Investigator Award, American Society for Investigative Pathology, 2002

  • The Society for the Study of Reproduction Research Award, 2002

  • Inaugural Ernst Knobil Lecture, University of Pittsburgh, 1998

  • The Bruce Stewart Memorial Lecture, American Society for Reproductive Medicine, 1998

  • Inaugural Billie Fields Reproductive Biology Lecture, University of Illinois, 2003

Representative Publications

  1. Li, Q., Graff, J.M., O'Connor, A.E., Loveland, K.L., and Matzuk, M.M. SMAD3 regulates gonadal tumorigenesis. Molecular Endocrinology In press (2007)
  2. Lin, Y.N., Roy, A., Yan, W., Burns, K.H., and Matzuk, M.M. Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Molecular and Cellular Biology 27, 6794-6805 (2007)
  3. Greenbaum, M.P., Ma, L., and Matzuk, M.M. Conversation of midbodies into germ cell intercellular bridges. Developmental Biology, 305, 389-396 (2007)
  4. Greenbaum, M., Yan, W., Wu, M-H., Lin, Y.N., Agno, J., Sharma, M., Braun, R.E., Rajkovic, A., and Matzuk, M.M. TEX14 is essential for intercellular bridge development and fertility in male mice. Proc. Natl. Acad. Sci., USA 103, 4982-87 (2006)
  5. Yatsenko, A.N., Roy, A., Chen, R., Ma, L., Murthy, L.J., Yan, W., Lamb, D.J., and Matzuk, M.M. Non-invasive genetic diagnosis of male infertility using spermatozoal RNA: KLHL10 mutations in oligozoospermic patients impair homodimerization. Human Molecular Genetics 15, 3411-3419 (2006)
  6. Rajkovic, A., Pangas, S.A., Ballow, D., Suzumori, N., and Matzuk, M.M. Nobox deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science 305: 115-117 (2004)
  7. Yan, W., Lang, M., Burns, K.H., and Matzuk, M.M. Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice. Proc. Natl. Acad. Sci., USA 101: 7793-7798 (2004)
  8. Burns, K.H., Viveiros, M.M., Ren, Y., Wang, P., DeMayo, F., Eppig, J.J., Frail, D.E., and Matzuk, M.M. Roles of NPM2 in chromatin and nucleolar organization in oocytes and embryos. Science 300:633-636 (2003)
  9. Wu, X., Viveiros, M.M., Eppig, J.J., Bai, Y., Fitzpatrick, S., and Matzuk, M.M. Zygote arrest 1 (Zar1) is a novel maternal effect gene critical for the oocyte-to-embryo transition. Nature Genetics 33:187-191 (2003)
  10. Burns, K.H., Agno, J.E., Sicinski, P., and Matzuk, M.M. Cyclin D2 and p27 are tissue-specific regulators of tumorigenesis in inhibin a knockout mice. Molecular Endocrinology 17:2053-2069 (2003)
  11. Matzuk, M.M., Burns, K.H., Viveiros, M.M., and Eppig, J.J. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296: 2178-2180 (2002)
  12. Matzuk, M.M. and Lamb, D.J. Genetic dissection of mammalian fertility pathways. Nature Medicine 8 (S1):S41-9 (2002)
  13. Brown, C.W., Houston-Hawkins, D.E., Woodruff, T.K., and Matzuk, M.M. Insertion of Inhbb into the Inhba locus rescues the Inhba -null phenotype and reveals new activin functions. Nature Genetics 25: 453-457 (2000)
  14. Kumar, T.R., Wang, Y., Lu, N., and Matzuk, M.M. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nature Genetics 15: 201-204 (1997)
  15. Dong, J., Albertini, D.F., Nishimori, K., Kumar, T.R., Lu, N., and Matzuk, M.M. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383: 531-535 (1996)
  16. Matzuk, M.M., Kumar, T.R., Vassalli, A., Bickenbach, J.R., Roop, D.R., Jaenisch, R., and Bradley, A. Functional analysis of activins in mammalian development. Nature 374: 354-356 (1995)
  17. Matzuk, M.M., Kumar, T.R., and Bradley, A. Different phenotypes for mice deficient in activins and activin receptor type II. Nature 374: 356-360 (1995)
  18. Matzuk, M.M., Lu, H., Vogel, H., Sellheyer, K., Roop, D.R., and Bradley, A. Multiple defects and perinatally death in mice deficient in follistatin. Nature 374: 360-363 (1995)
  19. Matzuk, M.M., Finegold, M.J., Su, J.-G.J., Hsueh, A.J.W., and Bradley, A. a-Inhibin is a tumour supressor gene with gonadal specificity in mice. Nature 360: 313-319 (1992)