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"Models to Study Cancer and Reproduction"
Martin M. Matzuk, MD, PhD
Stuart A. Wallace Chair and Professor
Department of Pathology & Immunology
Department of Molecular & Human Genetics
Baylor College of Medicine
To achieve a healthy pregnancy, the embryo and the uterus must establish a cross talk that will be essential throughout gestation. The implantation of the embryo takes place in a limited window of time when the uterus is receptive and the embryo has reached the proper stage of development. This crucial synchrony is controlled by the sex hormones through the regulation of the expression of many downstream factors; intriguingly, these factors are connected by mutual regulation and feedback loops that make this regulatory network challenging to decipher.
During the last two decades, our group has interrogated the roles of the transforming growth factor-beta (TGF-beta) signaling pathways in the mammalian reproductive tract through the creation of specific mutations of ligand and receptor genes. Our studies indicate that key ligand:receptor interactions are required for female fertility. Moreover, considering the broad involvement of the TGFβ superfamily in many processes, it is crucial to further dissect these pathways in ovarian and uterine biology to identify possible targets for future therapeutic manipulation.
MicroRNAs comprise a major class of small RNAs that have been shown to have roles in mammalian reproduction. miRNAs are 21-23 nucleotide small RNAs and are produced through the actions of the RNase III DICER. To study the global roles of microRNAs in female reproductive tract development, physiology, and disease (e.g., infertility and ovarian cancer), our laboratory has used conditional knockout approaches to ablate DICER and other key genes.
The importance of our findings can be fully appreciated if we consider that ~10 percent of U.S. women (6.1 million) ages 15-44 have difficulty getting pregnant or staying pregnant. In particular, 75% of the lost pregnancies are due to failure at the implantation stage. At the same time, unplanned pregnancy is a major healthcare problem. Our in vivo studies will be addressed in this presentation.
The research in our laboratory is supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Ovarian Cancer Research Fund.