Martin M. Matzuk
M.D., Ph.D., Washington University School of Medicine
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
Baylor College of Medicine, Building: Smith Medical
Research Bld
Room: BCMS-S217A
Phone: 713.798.6451
e-mail: mmatzuk@bcm.tmc.edu
RESEARCH INTERESTS:
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.
Selected Publications
Matzuk MM, Kumar TR, Vassalli A, Bickenback JR, Roop DR, Jaenisch R, and Bradley A: Functional analysis of activins in mammalian development. Nature 374:354-356, 1995.
Matzuk MM, Kumar TR, and Bradley A: Different phenotypes for mice deficient in either activins or acticin receptor type II. Nature 374:356-360, 1995.
Matzuk MM, Lu H, Vogel H, Sellheyer K, Roop DR, and Bradley A: Multiple defects and perinatally death in mice deficient in follistatin. Nature 374:360-363, 1995.
Nishimori K, Young LJ, Guo Q, Wang Z, Insel TR, and Matzuk MM: Oxytocin is required for nursing but is not essential for parturition or reproductive behavior. Proc. Natl. Acad. Sci. USA 21:11699-11704, 1996.
Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, and Matzuk MM: Growth differentiation factor-9 is required during early folliculogenesis. Nature 383:531-535, 1996.
Kumar TR, Wang Y, Lu N, and Matzuk MM: Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nature Genetics 15, 201-204, 1997.