Arthur R. Strauch, III, Ph.D.

Professor 314 Biomedical Research Tower 460 W. 12th Avenue Columbus  OH  43210 strauch.1@osu.edu

Education:
B.Sc., Cell and Molecular Biology, McGill University, Montreal, Canada
Ph.D., Cell and Molecular Biology, State University of New York, Buffalo, NY

Research Area:
Actin protein biochemistry
Vascular smooth muscle alpha-actin gene expression
Smooth muscle development and phenotypic switching
Pathogenesis of proliferative vascular diseases, e.g. arteriosclerosis
Cardiac transplantation and allograft remodeling

Research Interests:
Biosynthesis of the muscle contractile protein referred to as alpha-actin in isolated vascular smooth muscle cells is coupled to extracellular microenvironmental conditions. Many of the changes that accompany modulation of smooth muscle cell phenotype in culture actually develop in the human population as a consequence of heart transplantation, post-angioplasty coronary artery restenosis, pulmonary hypertension, and arteriosclerosis. Changes in the expression of essential contractile proteins such as actin in the blood vessel wall are linked to altered cell behavior and abnormal cardiovascular performance. Our molecular cardiovascular research laboratory is located in the Dorothy M. Davis Heart and Lung Research Institute and has been funded over the past 24 years through grants from the National Heart, Lung and Blood Institute of the National Institutes of Health and the American Heart Association. Major areas of current research emphasis include:
(1) identifying gene promoter regulatory elements and their cognate DNA-binding proteins that mediate expression of actin in vascular smooth muscle and cardiac muscle,
(2) studying the etiology and molecular pathobiology of cardiovascular remodeling and allograft chronic rejection following heart transplant, and
(3) understanding the regulation and role of vascular smooth muscle actin gene expression during wound healing, myofibroblast differentiation, fibrosis, and maladaptive organ reconstruction in chronic inflammatory diseases of the heart, lung, liver, and kidney.

Cardiac transplantation is accompanied by dysfunctional remodeling of the donor heart that limits transplant patient well-being and long-term survival. Research in the Art Strauch lab in the Dorothy M. Davis Heart & Lung Research Institute is directed toward understanding adverse changes in gene expression that can disrupt adaptation of donor hearts to their new hosts. Toward that goal, we have discovered that the mRNA-binding protein, Pur alpha, accumulates at cardiac intercalated discs after transplant (dark lines in panel b). Normal, non-transplanted hearts do not contain Pur alpha (panel a). Intercalated discs are a major site for protein synthesis and contractile filament assembly in heart muscle. While some discs contain only Pur alpha (boxed area in panel c), the majority of discs in transplanted hearts contain Pur alpha in close spatial association with elongating smooth muscle alpha-actin contractile filaments that look like “comet tails” (arrows, panel c). Spatial relationships between Pur alpha-bound actin mRNA molecules and synthesis of actin contractile filaments at intercalated discs potentially represents a new tool for evaluating destructive tissue remodeling after heart transplant.

Representative Publications:
• Zhang A, David JJ, Subramanian SV, Liu X, Fuerst MD, Zhao X, Leier CV, Orosz CG, Kelm Jr RJ, Strauch AR. Serum response factor neutralizes Pur alpha and Pur beta-mediated repression of the fetal vascular smooth muscle alpha-actin gene in stressed adult cardiomyocytes. Am J Physiol Cell Physiol, in press, March 2008.
• Knapp AM, Ramsey JE, Wang SX, Strauch AR, Kelm RJ Jr. Structure-function analysis of mouse Pur beta II. Conformation altering mutations disrupt single-stranded DNA and protein interactions crucial to smooth muscle alpha-actin gene repression. J Biol Chem. 282(49):35899-909, 2007.
• Roy S, Khanna S, Rink T, Radtke J, Williams WT, Biswas S, Schnitt R, Strauch AR, Sen CK. 21waf1/cip1/sdi1 as a central regulator of inducible smooth muscle actin expression and differentiation of cardiac fibroblasts to myofibroblasts. Mol Biol Cell. 18(12):4837-46, 2007.
• Martin AF, Bhatti S, Pyne-Geithman GJ, Farjah M, Manaves V, Walker L, Franks R, Strauch AR, Paul RJ. Expression and function of COOH-terminal myosin heavy chain isoforms in mouse smooth muscle. Am J Physiol Cell Physiol. 293(1):C238-45, 2007.
• Zhao X, Chen YR, He G, Zhang A, Druhan LJ, Strauch AR, Zweier JL. Endothelial nitric oxide synthase (NOS3) knockout decreases NOS2 induction, limiting hyperoxygenation and conferring protection in the postischemic heart. Am J Physiol Heart Circ Physiol. 292(3):H1541-50, 2007.
• Zhang A, Liu X, Cogan JG, Fuerst MD, Polikandriotis JA, Kelm RJ Jr, Strauch AR. YB-1 coordinates vascular smooth muscle alpha-actin gene activation by transforming growth factor beta1 and thrombin during differentiation of human pulmonary myofibroblasts. Mol Biol Cell. 16(10):4931-40, 2005.
• Knapp AM, Ramsey JE, Wang SX, Godburn KE, Strauch AR, Kelm RJ Jr. Nucleoprotein interactions governing cell type-dependent repression of the mouse smooth muscle alpha-actin promoter by single-stranded DNA-binding proteins Pur alpha and Pur beta. J Biol Chem. 281(12):7907-18, 2006.

Research Funding:
• National Institutes of Health, National Heart, Lung and Blood Institute, RO1 HL 085109, Targeting Myofibroblast Activation in Chronic Fibrotic Disease, $1,000,000 (direct costs), $1,500,000 (total costs), December 2007-November 2011, Arthur R. Strauch, Ph.D., Principal Investigator.