I received my Ph.D. in Physiology from Michigan State University in East Lansing, MI in 1984. I spent 2 years at the University of Michigan in Ann Arbor, MI and 5 years at the University of Vermont in Burlington, VT as a post-doctoral fellow. I was a Research Scientist at the University of Iowa in Iowa City, IA for 5 years. I joined the faculty at the University of Maryland, Baltimore in 1996 in the Dept. of Obstetrics, Gynecology and Reproductive Sciences and have a secondary appointment in the Dept. of Physiology. I am a member of the Center for Studies in Reproduction at UMB, The American Physiological Society, The Perinatal Research Society and The Society for Gynecological Investigation.

Chronic hypoxia (or reduced fetal oxygenation) is the leading cause of fetal morbidity and mortality. The fetus’s ability to adapt to hypoxia depends on the length and severity of the exposure and may result in intrauterine growth restriction, fetal brain damage and death due to myocardial failure. Epidemiological studies have identified a strong association between reduced fetal growth and an increased risk of adult cardiovascular disease suggesting that fetal health impacts the adult. We are interested in the mechanisms responsible for how chronic hypoxia reduces fetal growth and may alter fetal vascular function in an organ specific manner. The goal of our research effort is to understand how chronic hypoxia programs the fetal cardiovascular system and alters blood flow regulation and vascular reactivity, both in the fetus and after birth.

A reduction in oxygen levels has been shown to stimulate the expression of a variety of oxygen-sensitive genes as an adaptive mechanism for cell survival. Further, the vascular endothelium has been shown to be an oxygen-sensing site for synthesis and release of endothelium-derived relaxing factors such as nitric oxide (NO). Thus, our research efforts focus on the effect of fetal hypoxia on the expression of oxygen-sensitive genes such as nitric oxide synthase and how altered gene expression influences the regulation of blood vessel responsiveness in the fetus and after birth.

Research Areas Currently Under Investigation:

HYPOXIA-INDUCED MODULATION OF THE FETAL CARDIOVASCULAR SYSTEM

The effect of chronic hypoxia on blood pressure regulation of the fetal cardiovascular system has been intensely studied for many years. However, it has been only recently that cellular mechanisms of vascular smooth muscle and the endothelium have been investigated in the fetus. Vascular responsiveness is measured in isolated fetal arteries using an isolated wire myograph for measurement of isometric contractile force and in pressurized, cannulated artery segments for measurement of vessel diameter changes using videomicroscopy. Coronary flow responses are measured using an isolated, pressure-perfused fetal heart preparation. We found that chronic hypoxemia alters fetal artery reactivity by increasing endothelium-dependent NO synthase activity and alters the regulation of the fetal coronary flow responses through endothelium-dependent mechanisms mediated by NO, prostaglandins and endothelium-derived hyperpolarizing factor.

NITRIC OXIDE (NO) SYNTHASE GENE EXPRESSION IN FETAL ORGANS.

NO is a potent endothelium-derived relaxing factor, important in modulating vascular tone. We measure the effect of hypoxia on gene expression of NO synthase, a synthetic enzyme that produces NO, in a variety of fetal organs including heart, blood vessels and brain. We utilize ribonuclease protection assay to measure mRNA levels, Western blot analysis to measure protein levels and enzymatic assays to measure activity of the three NO synthase isoforms (constitutive NOS (Type III), inducible NOS (Type II) and neuronal NOS (Type I).