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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

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

Post-doctoral Training

  1. Resident, Clinical Pathology, Hospital of the University of Pennsylvania, 1990-1991

  2. Resident and Postdoctoral Fellow, Baylor College of Medicine, 1991-1993

Board Certification

  1. American Board of Pathology, Clinical Pathology, 2006

Area of Interest

  1. The Matzuk laboratory focuses on defining fertility and cancer pathways in the mammalian reproductive tract. To study these processes, our group has created an extensive assortment of invaluable mouse models that have helped to decipher TGF b superfamily and hormonal signaling pathways that effect reproductive development, physiology, and cancer. These studies have led to the identification of the endocrine hormone, inhibin, as a secreted tumor suppressor with specificity for the gonads and adrenals. Whereas mammalian oocytes were initially thought to be merely passengers rather than drivers in ovarian development, our group demonstrated that the oocyte-secreted TGF b family member, growth differentiation factor 9 (GDF9), was essential for ovarian folliculogenesis at the primary follicle stage. These initial insights with GDF9 and bone morphogenetic protein 15 (BMP15), the other oocyte-specific TGF b superfamily member that our group discovered, have helped us to define the key factors involved in germ cell-somatic cell dialog orchestrating the many steps in ovarian folliculogenesis.

  2. The Matzuk laboratory was also the first to show that activins signal specifically through activin receptor type 2 to regulate FSH synthesis and that FSH was required for female but not male fertility. Our group has also discovered key spermatogenic genes ( e.g. , TEX14, the first essential mammalian germ cell intercellular bridge protein). These studies have allowed us to develop novel screening strategies for infertile men and to identify potential targets for male-specific contraception. Furthermore, our research is also directed at defining the roles of small RNAs in the female and male reproductive tracts and in ovarian cancer, and we have shown that absence of the precursor miRNA-processing enzyme DICER is required for fertility in females.

Current Positions

  1. Professor, Department of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics, Baylor College of Medicine, 1998-Present

  2. Stuart A. Wallace Chair in Pathology, Baylor College of Medicine, 1999-Present

  3. Associate Chair for Research, Department of Pathology, Baylor College of Medicine, 2007-Present

  4. Director of Clinical Chemistry and Associate Director of Diagnostic Immunology, Ben Taub General Hospital, 1993-Present

  5. Co-Director of the Medical Scientist Training Program, Baylor College of Medicine, 1994-Present

Honors and Awards

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

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

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

  4. The HypoCCS Award, Eli Lilly, 1999

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

  6. NIH MERIT Award, R01HD33438, May 1, 2001

  7. Pfizer Outstanding Investigator Award, American Society for Investigative Pathology, 2002

  8. The Society for the Study of Reproduction Research Award, 2002

  9. Inaugural Ernst Knobil Lecture, University of Pittsburgh, 1998

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

  11. Inaugural Billie Fields Reproductive Biology Lecture, University of Illinois, 2003

Representative Publications

  1. Matzuk, M.M. and Lamb, D.J. The biology of infertility: research advances and clinical challenges. Nature Medicine 14, 1197-1213 (2008).

  2. Nagaraja, A.K., Andreu-Vieyra, C., Franco, H.L., Ma, L., Chen, R., Han, D.Y., Zhu, H., Agno, J.E., Gunaratne, P.H., DeMayo, F.J., and Matzuk, M.M. Deletion of Dicer in somatic cells of the female reproductive tract causes sterility. Molecular Endocrinology 22, 2336-2352 (2008).

  3. Li, Q., Pangas, S.A., Jorgez, C.J., Graff, J.M., Weinstein, M., and Matzuk, M.M. Redundant roles of SMAD2 and SMAD3 in ovarian granulosa cells in vivo. Mol Cell Biol 28, 7001-7011 (2008).

  4. Aitken, J.R., Baker, M.A., Doncel, G.F., Matzuk, M.M., Mauck, C.K., Harper, M.J.K. As the world grows: contraception in the 21 st century. Journal of Clinical Investigation 118, 1330-1343 (2008).

  5. Creighton, C.J., Nagaraja, A.K., Hanash, S.M., Matzuk, M.M., and Gunaratne, P.H. A bioinformatics tool for linking gene expression profiling results with public databases of microRNA target predictions. RNA 14, 2290-6 (2008).

  6. Pangas, S.A., Li, X., Umans, L., Zwijsen, A., Huylebroeck, D., Gutierrez, C., Wang, D., Martin, J.F., Jamin, S.P., Behringer, R.R., Robertson, E.J., and Matzuk, M.M. Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol 28, 248-257 (2008).

  7. Pangas, S.A., Jorgez, C.J., Tran, M., Agno, J.E., Li, X., Brown, C.W., Kumar, T.R., and Matzuk, M.M. Intraovarian activins are required for female fertility. Molecular Endocrinology 10, 2458-71 (2007).

  8. Li, Q., Graff, J.M., O'Connor, A.E., Loveland, K.L., and Matzuk, M.M. SMAD3 regulates gonadal tumorigenesis. Molecular Endocrinology 21, 2472-86 (2007)

  9. 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)

  10. Greenbaum, M.P., Ma, L., and Matzuk, M.M. Conversation of midbodies into germ cell intercellular bridges. Developmental Biology, 305, 389-396 (2007)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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)

  17. 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)

  18. 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)

  19. Matzuk, M.M. and Lamb, D.J. Genetic dissection of mammalian fertility pathways. Nature Medicine 8 (S1):S41-9 (2002)

  20. 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)

  21. 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)

  22. 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)

  23. 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)

  24. 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)

  25. 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)

  26. 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)