This is the applicant's third year of the first faculty appointment at UT Medical School Houston. She is an Assistant Professor of Pathology with subspecialties in renal and pediatric/perinatal pathology and wishes to pursue the laboratory investigation of preeclampsia using clinical collaborations to provide patient material and data. The experiments focus on the placenta and kidney relating the project to the applicant's clinical expertise. Collaborative study of the renin angiotensin system in pregnancy and preeclampsia began two years ago with the applicant's mentor, Dr. Rodney E. Kellems, Ph.D. The applicant has access to a large obstetric service and to a molecular biology laboratory with ongoing investigations in vascular biology, placental development and implantation, and pregnancy in murine models. The applicant's mentor, Dr. Kellems, Professor and Chairman of Biochemistry and Molecular Biology at the medical school, is a primary investigator with a long record of training doctoral candidates and postdoctoral fellows in molecular genetics and biology. The applicant has two clinical co-mentors providing guidance for the clinical collaborations. The training plan includes two years of clinical research training and formal courses in molecular biology, molecular genetics, and immunology. The laboratory experiments will continue for five years, overlapping in the first two years with a clinical curriculum. Preeclampsia complicates 5-10% of pregnancies. The disorder has been extensively studied, but the pathogenesis remains unknown. Initial symptoms, hypertension and proteinuria, may herald seizures or death. Fetal morbidity and mortality are high because treatment, delivery, is often premature. Major target organs are the placenta and kidney. In vitro use of patient serum will provide insight into the effects of circulating factors on these organs. The experiments uniquely focus on trophoblast and kidney glomerular cells. The work specifically investigates the recent claim that agonistic antibodies to the AT1 receptor of angiotensin II (AT1-AA) may have a causal role in the disorder. We will be the first to confirm these antibodies and the first to test the cause and effect relationship between AT1-AA and preeclampsia in a cohort study.
