Professor, Baylor College of Medicine
Co-Director, M.D./Ph.D. – Medical Scientist Training Program
Stuart A. Wallace Professor
B.A., University of Chicago, IL, 1982
M.D./Ph.D., Washington University School of Medicine, St. Louis, MO, 1989
Postdoc, Baylor College of Medicine, Houston, 1991-93
Oncogenesis, reproduction, and development in mice
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-β 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.
Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM (2004) NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science 305:1157-1159.
Jorgez CJ, De Mayo FJ, Matzuk MM (2006) Inhibin alpha-iCre mice: Cre deleter lines for the gonads, pituitary, and adrenal. Genesis 44:183-188.
Greenbaum MP, Ma L, Matzuk MM (2007) Conversion of midbodies into germ cell intercellular bridges. Developmental Biology 305:389-396.
Lin YN, Roy A, Yan W, Burns KH, Matzuk MM (2007) Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Molecular and Cellular Biology 27:6794-6805.
Ma L, Buchold GM, Greenbaum MP, Roy A, Burns KH, Zhu H, Han DY, Harris RA, Coarfa C, Gunaratne PH, Yan W, Matzuk MM (2009) GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline. PLoS Genetics 5:e1000635.
Andreu-Vieyra CV, Chen R, Agno JE, Glaser S, Anastassiadis K, Stewart AF, Matzuk MM (2010) MLL2 is required in oocytes for bulk histone 3 lysine 4 trimethylation and transcriptional silencing. PLoS Biology 8:e1000453.
Hawkins SM, Creighton CJ, Han DY, Zariff A, Anderson ML, Gunaratne PH, Matzuk MM (2011) Functional microRNA involved in endometriosis. Molecular Endocrinology 25:821-832.
Hawkins SM, Andreu-Vieyra CV, Kim TH, Jeong JW, Hodgson MC, Chen R, Creighton CJ, Lydon JP, Gunaratne PH, DeMayo FJ, Matzuk MM (2012) Dysregulation of uterine signaling pathways in progesterone receptor-Cre knockout of dicer. Molecular Endocrinology 26:1552-1566.
Kim J, Coffey DM, Creighton CJ, Yu Z, Hawkins SM, Matzuk MM (2012) High-grade serous ovarian cancer arises from fallopian tube in a mouse model. Proceedings of the National Academy of Sciences USA 109:3921-3926.
Matzuk MM, McKeown MR, Filippakopoulos P, Li Q, Ma L, Agno JE, Lemieux ME, Picaud S, Yu RN, Qi J, Knapp S, Bradner JE (2012) Small-molecule inhibition of BRDT for male contraception. Cell 150:673-684.
Martin M. Matzuk, M.D., Ph.D.
Department of Pathology
Baylor College of Medicine
One Baylor Plaza S217
Houston, Texas 77030, U.S.A.
Tel: (713) 798-6451
Fax: (713) 798-5838