Kelle H. Moley, M.D.
Associate Professor in Obstetrics and Gynecology and Cell Biology and Physiology
Director of Research, Division of Reproductive Endocrinology and Infertility
Fellowship Director, Reproductive Endocrinology and Infertility
Dr. Moley is currently working with BIRCWH Scholar Mary Carayannopoulos, Ph.D., on a project titled “Deciphering the Molecular Mechanisms Involved in Diabetes Associated Congential Malformations”
Research Focus
Dr. Moley studies how early preimplantation glucose transport and metabolism affect the fate and outcome of pregnancy at a molecular level. Glucose enters the blastocyst via one of five facilitative glucose transporters, GLUT1, GLUT2, GLUT3, GLUT8, and GLUT9 (the last two were recently cloned by Kelle’s group). Maternal hyperglycemia leads to down regulation of GLUT1-3 at the blastocyst stage in the mouse, which triggers apoptosis via effector pathways involving BAX, p53 and caspases. In the diabetic state, a threshold of appropriate glucose concentration is crossed, apoptosis is triggered, and fetal resorption or malformations ensue. The Moley lab is focusing on how decreased intracellular glucose triggers apoptosis causing pregnancy loss or malformation using GLUT1 antisense expressing mice and genetic models of diabetes. The group is also investigating how diabetes affects oocyte quality, maturation and potential to develop into normal embryos using genetic models as well as zygote and ovarian transplantation techniques. Dr. Moley has also demonstrated that hyperinsulinemia and high IGF-1 levels associated with polycystic ovary syndrome lead to decreased insulin-stimulated glucose transport, a decrease in intracellular glucose levels and increased apoptosis. Studies are ongoing to define the role of GLUT8 and insulin signaling pathways in these processes using trophectoderm stem cell and embryonic stem cell systems. GLUT9 is another embryonically expressed transporter existing as splice variants that are differentially expressed in polarized epithelial cells. The lab is actively studying the motifs responsible for the targeting of the different forms, transcriptional regulation of these isoforms and the function of these transporters in the polarized epithelium of blastocysts and blastocyst-derived cells. Scholars in the Moley lab will have a research experience that includes exposure to glucose transport physiology and apoptotic signaling pathways in preimplantation murine embryos and oocytes, single embryo analysis using enzymatic cycling assays for metabolite and enzyme activity assessment, immunofluorescent and electron microscropy, and a variety of molecular techniques in the pursuit of one of the most critical problems in women’s health, infertility.
