My research centers on the physiological mechanisms underlying the normal maternal physiological responses to pregnancy and the pregnancy complications of fetal growth restriction and preeclampsia. I use the chronic hypoxia of residence at high altitude (>2500 m or 8000 ft) as a natural laboratory for studying these mechanisms since high altitude exerts one of the strongest influences on fetal growth (being second in magnitude only to gestational age) and triples the frequency of preeclampsia. With students, fellows and faculty colleagues from obstetrics & gynecology and other disciplines (anesthesiology, anthropology, cancer biology, genetics, medicine, pediatrics, physiology, and public health) and the aid of NIH, NSF or other federal funding, we have published more than 200 articles documenting the effects of chronic hypoxia on maternal and fetal well being. In particular our human studies have shown that altitude lowers birth weight an average of 102 g/1000 m and is associated with less pregnancy-associated rise in uterine artery blood flow, due in turn to smaller uterine artery diameters. Experimental animal studies have shown that chronic hypoxia vs. normoxia reduces uterine artery nitric oxide production, vasodilator response to flow, growth and remodeling, suggesting that chronic hypoxia interferes with the normal maternal uterine vascular responses to pregnancy. Multigenerational populations (Andeans, Tibetans) are largely protected from hypoxia-associated fetal growth restriction, due in part to being able to attain greater uterine artery diameter and blood flow than shorter-term residents (Europeans, Chinese). Our recent whole-genome scan and gene-expression studies have identified several genes likely involved. Current work is aimed at identifying the specific gene variants and physiological mechanisms by which they exert their effects with hopes that such studies will aid not only in understanding processes of evolutionary adaptation but also our ability to identify persons at risk for pregnancy complications and/or design more effective therapies for their treatment or prevention.