Dr. Keigi Fujiwara
The University of Texas MD Anderson Cancer Center
Department of Cardiology
I was trained as a cell biologist specialized in cell motility such as cell migration, cell division, intracellular organelle trafficking, and cell contraction. Our studies on the cytoskeleton of endothelial cells led us to the field of cellular mechanosensing and mechanosignaling. Using flow and cell stretch apparatuses we designed, we are studying endothelial cell responses to mechanical forces and the role of such forces on vascular pathogenesis. Through a series of in vitro cell and molecular biological studies, we were able to identify platelet endothelial cell adhesion molecule 1 (PECAM-1/CD31) to be a mechanosensor molecule of endothelial cells. The precise mechanism for mechanotransduction by PECAM-1 is being investigated. Our studies are also aimed at endothelial cell biology and physiology, especially on topics related to the cytoskeleton and cell adhesion and to cell signaling in the context of atherogenesis and endothelial dysfunction. In the past several years, I am collaborating with Dr. Jun-ichi Abe, Professor, UT MD Anderson Cancer Center, to study signaling events in endothelial cells that are exposed to disturbed flow. Identifying signaling molecules activated specifically by disturbed flow is an important step towards the discovery of new pharmacologic interventions against atherosclerosis and other cardiovascular diseases. Our studies are also focused on negative effects of cancer treatments on the cardiovascular system (cardio-oncology), which has become a critical issue for cancer patients and survivors in recent years. Radiotherapy is a common anti-cancer treatment. During this treatment, normal tissues are also exposed to irradiation and triggers pathological responses in them. For this reason, we are also studying intracellular signaling induced by radiation. Such studies lead us to a NASA study in which effects of space radiation (and microgravity) on astronauts as well as on cultured cells, and we found increased chromosome aberrations and changes in posttranslational modifications of proteins.