William T. Gerthoffer, Ph.D.
Professor and Chair
Ph.D., West Virginia University, 1978
My lab investigates regulation of vascular and airway smooth muscle contraction and regulation of smooth muscle phenotype. Contraction of smooth muscle and movement of nonmuscle motile cells is caused by calcium activating the contractile proteins, actin and myosin. Several constituents of the contractile element of mammalian smooth muscle are phosphorylated by protein kinases during contraction. Some proteins of current interest include the small heat shock proteins, HSP27 and HSP20. Protein phosphorylation and protein kinase cascades are studied using immunological methods, cell culture models, adenovirus and retroviral vectors for gene transfer and molecular methods of protein biochemistry. Biophysical techniques used to measure smooth muscle function are correlated with the phosphorylation state of the contractile proteins and small heat shock proteins to test current ideas about of actin remodeling in smooth muscle contraction and cell motility.
Our current research is focused on the role of small noncoding RNAs in determining smooth muscle phenotype. Smooth muscle phenotype varies during development, during vascular remodeling and in inflammatory diseases including atherosclerosis, asthma and inflammatory bowel disease. The lab is investigating the role of microRNAs in determining smooth muscle cell functions including contraction, cell migration and synthesis of cytokines and chemokines.
Interest in miRNAs in smooth muscle has evolved rapidly to studies of miRNAs as both therapeutic targets and therapeutic agents. We are using a rat model of pulmonary arterial hypertension (PAH) and the house dust mite mouse model of asthma to develop novel miRNA-based drugs that can be delivered to the lungs to reverse pathological vascular remodeling.
Another current interest of the lab is the study of plasma protein and miRNA biomarkers in humans with coronary artery disease. We hope to test the validity of circulating HSP27, pregancy-associated plasma protease-A and miRNAs in predicting risk of acute coronary syndrome in humans. Our study population has a high percentage of medically underserved individuals for whom inexpensive, noninvasive biomarkers of acute coronary syndrome would be highly beneficial.
miRNA-based therapy of animal models of pulmonary arterial hypertension and asthma
miRNA determinants of the asthmatic phenotype of human airway smooth muscle cells
HSP27 and pregnancy-associated plasma protein A as biomarkers of atherosclerotic plaque stability
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