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Vincent Center for Reproductive Biology
A major effort in the laboratory of Bo Rueda, PhD, has been in the identification and functional characterization of gynecological cancer cells.
Director, Vincent Center for Reproductive Biology, Massachusetts General HospitalDirector, Clinical Fellows Research Program, Department of Obstetrics and Gynecology, Massachusetts General HospitalDirector, Deborah Kelly Center for Outcomes Research, Massachusetts General HospitalAssociate Professor, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical SchoolAffiliated Faculty, Harvard Stem Cell InstituteAffiliated Faculty, Massachusetts General Hospital Cancer Center
A major effort in Dr. Rueda’s laboratory has been in the identification and functional characterization of gynecologic cancer stem cells. Recent experiments conducted in collaboration with Dr. Rosemary Foster provide evidence to support the concept that both human endometrial and ovarian cancers contain a rare subpopulation of tumor-initiating cells, which have stem/progenitor like properties (Cell Cycle 2008; 7:242-249; 2009; 27:2875-83; Cancer Research 2009; 69:8241-8.). Drs. Rueda and Foster are actively optimizing strategies to better isolate these rare cells, define their stem like properties, determine how they are regulated, how their local environment may influence them, whether they are resistant to current radiation or chemotherapy and ultimately how we may target them.
Another component of Dr. Rueda’s research is the molecular interrogation of human gynecologic tumors to test novel anti-cancer drugs in a pre clinical setting. This research is part of an active consortium with Dr. Darrell Borger of the Translational Research Laboratory (MGH Cancer Center) and Dr. Whitfield Growdon (VCRB MGH Obstetrics and Gynecology Department). Together they have been actively developing strategies for real-time identification of novel cell signaling pathways that contribute to malignant transformation (Gyn Onc 2008; 111:289-297), the pathology of the disease and/or chemoresistance and recurrence in gynecologic cancers. Once identified, they are testing new biologics and determining their efficacy in primary ovarian and/or endometrial tumor explant and short-term cell culture models. The results of this research will hopefully contribute to development of strategies designed to provide patients personalized therapy.
A long standing basic science theme of Dr. Rueda’s research has been defining the functional significance of mediators of cell proliferation and/or differentiation in ovarian and uterine biology. This is a critical step in the dynamic cellular changes associated with the hormone mediated menstrual cycle. Inactivation of specific cell cycle regulators can promote cellular hyperplasia and malignant transformation. Dr. Rueda’s team has been working to identify novel hormone mediated cell cycle regulators and their interacting proteins to determine their functional significance in the regulation of the cell cycle, cell proliferation, differentiation and/or apoptosis (Cancer Res 2004;202-8; Can Biol Ther 2005;103-107; Can Biol Ther 2007;15:7).
It is well recognized that endometriosis is a polygenic disease with complex multifactorial etiologies affecting reproductive-aged women. Although this disorder is commonly treated in clinical practice, the mechanisms by which ectopic endometrium is disseminated and proliferates, is not completely understood. There are a number of different factors, which have been implicated in either the genesis or the propagation of endometriosis. They include but are not limited to prostaglandins, cytokines, growth factors, chemokines, cell adhesion molecules and steroid hormones. It is, however, difficult to investigate the functional role of these factors without adequate in vivo model systems. Dr. Styer and Dr. Rueda continue to develop and exploit existing mouse models which have been manipulated to ‘mimic’ the human disease in order that they may study the effect of specific factors on the growth of ectopic endometrium (Endocrinology 2008; 149:506-514). The mouse model was chosen to incorporate the power of mouse genetics. Using mutant mouse strains that are devoid or over express one or more of the factors described above they should be able to delineate their cause an effect relationships with the pathogenesis of the disease. Using this strategy in tandem with gene and protein analysis Dr. Styer and Dr. Rueda hope to gain a better understanding of the underlying mechanisms of endometriosis. This information will also serve to develop more effective alternative treatment modalities.
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