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melons Spermatogonial Stem Cells
In males, fertility requires the continuous and dynamic action of specialized but rare stem cells known as spermatogonia. We have discovered that a forkhead transcription factor, Foxo1, is specifically expressed in these cells and controls their maintenance and differentiation, and is thus required for male fertility. We are expanding our efforts in this area to understand at the molecular level how Foxo1 is regulated and in turn works with other Foxo family members to regulate gene expression in spermatogonial stem cells. These studies have broader implications for our understanding of stem cell function in adult tissues.
To read more, please follow this link: Goertz et al, Journal of Clinical Investigation 2011. [Goertz, PDF]

eggsOvarian aging, female infertility, and early menopause syndromes
There is a growing appreciation for the importance of the ovary—particularly the number of eggs within the ovary—in regulating overall health. As women age, the number of eggs (primordial follicles) within the ovary decreases dramatically, and their eventual depletion leads to the menopause. We have been studying the biology of primordial follicle maintenance, seeking an understanding of the molecular pathways that maintain and preserve this precious resource throughout life. We discovered that the forkhead transcription factor Foxo3 controls the preservation of eggs in the ovary, a finding with major implications for the menopause and infertility/early menopause syndromes such as primary ovarian insufficiency (POI), also known as premature ovarian failure (POF). We have identified several of the molecular steps by which the PI3K signalling pathway controls Foxo3 to regulate the maintenance of eggs. Current work in our laboratory employs rigorous genetic and cell biological approaches to deepen our understanding of the workings of this pathway. To read more, please follow these links: Tarnawa et al, Biology of Reproduction 2013 [Tarnawa, PDF]; Sullivan and Castrillon, Seminars in Reproductive Medicine 2011 [Sullivan, PDF]; John et al, Developmental Biology 2008. [John, PDF]

mouseThe LKB1 tumor suppressor in women's cancers
Our laboratory has special interests in research relating to women's health, particularly infertility and cancer. The major focus of our cancer studies is the tumor suppressor gene LKB1. We have shown that the LKB1 gene is frequently mutated in cervical (uterine) cancer, the first recurring mutation identified in this common and clinically-important cancer. Our studies suggest that LKB1 inactivation is associated with particularly aggressive clinical behavior, and may thus warrant more vigorous clinical interventions. We have also explored the role of LKB1 in endometrial cancer (cancer of the lining of the uterus) using the Sprr2f-Cre transgene that we developed for conditional gene targeting within endometrial epithelium. This work led to an important LKB1-based model of invasive endometrial cancer. Current studies are aimed at the refinement of these genetic model systems to further study and understand the role of LKB1 in cancers of the reproductive tract, with the ultimate goal of developing therapies effective against tumors deficient for LKB1. More recently, we have shown that LKB1 can be used as an effective biomarker in human tumors, and may someday be useful in predicting outcome or treatment responses. To read more, please follow these links: Wingo et al, PLoS ONE 2009 and Contreras et al, Disease Models and Mechanisms, 2010. [Wingo PDF, Contreras PDF]