Thomas S. Walker, PhD

My laboratory focuses on working out the mechanisms by which bacteria cause disease. For many years, our research has centered on the means by which the obligately intracellular organism Rickettsia prowazekii causes the clinical signs of typhus. Rickettsiae are introduced into a human host via the bite of an infected body louse, and. invade the endothelial cells that line blood vessels. Patients develop high fever and a red rash. In severely ill patients, blood vessels leak fluid into the surrounding tissues, clots form in the microvasculature, and the volume of the circulating blood decreases dramatically. As a result, blood vessels collapse, blood flow to critical organs is cut off, and the patient's blood pressure drops dangerously low. Death usually is due to lack of blood supply to major organs or to shock. We culture endothelial cells obtained from a variety of sources, including human umbilical veins and the microvasculature. Purified rickettsiae are used to infect cultured endothelial cells or cells involved in the immune response. We examine the effects of infection on the ability of host cells to produce substances that normally control blood clotting, aggregation of platelets, vascular permeability, blood pressure, and immune processes. For example, we have shown that rickettsiae possess an enzyme (phospholipase A 2) that dissolves the host cell membrane. The affected cells convert the products of this enzyme's activity (arachidonic acid and lysophosphatides) into chemicals that cause blood vessels to dilate and become extremely permeable, and are significant participants in systemic and local inflammation. We also have looked at changes in host cell receptors and would like to look at the effects of these organisms on the host cell's life cycle. Other studies in our laboratory have examined the pathogenesis of Rocky Mountain spotted fever; the pathogenesis of bacterial meningitis; mechanisms of lupus anticoagulants; the pathogenesis of bacillary angiomatosis in AIDS patients; and the efficacy of new antibiotics.