melons Germ cells, pediatric and adult germ cell tumors, and infertility
We have long-standing interests in the biology of germ cells, the cells that give rise to gametes. These cells are required for male and female fertility but also give rise to diverse malignancies of the testis and ovary. 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 spermatogonial stem cells and the primordial germ cells from which they are ultimately derived are maintained and regulated in the testis and early embryo. These studies have broad implications for our understanding of infertility and germ cell malignancies, which are common in children, adolescents, and young adults. To read more, please follow this link: Goertz et al, Journal of Clinical Investigation 2011. [Goertz, PDF]

mouseMolecular basis of uterine cancer (a.k.a. endometrial cancer)
Our laboratory also has special interests in research relating to women's health, particularly cancer of the uterus. One focus of our studies on cancer of the endometrium (the lining of the uterus) has been 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 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 and other recently-discovered uterine cancer genes, with the ultimate goal of developing targeted therapies effective against tumors harboring these specific genetic alterations. 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; and Akbay et al, Oncogene, 2013. [Wingo PDF, Contreras PDF, Akbay PDF]