INDIVIDUAL RESEARCHER
Dale D. Tang
, M.D.
, Ph.D.
Associate Professor
e-mail: tangd@mail.amc.edu
Education
- M.D. from Tonji Medical University, Wuhan, China- Ph.D. from Tonji Medical University, Wuhan, China
Current Research
View the Cytoarchitecture of Smooth Muscle Cells
Airflow in the respiratory system and vascular tone are largely regulated by smooth muscle in the airway and vasculature. Aberrant status of smooth muscle contraction leads to the development of respiratory and vascular diseases such as asthma and essential/renal hypertension. There is a wealth of evidence that contractile stimuli play an essential role in the pathogenesis of asthma and hypertension. However, the mechanisms by which the constrictors regulate smooth muscle contractility are not completely understood. Based on the observations by other investigators and my laboratory, we propose that the functional changes in the cytoskeleton of smooth muscle may profoundly influence force development. Specifically, we attempt to understand the role and regulation of the intermediate filament framework and the actin lattice in the context of smooth muscle cells. Previous studies from knockout mice and antisense oligodeoxynucleotides have demonstrated that intermediate filament proteins are required for normal smooth muscle contraction. However, the mechanisms by which these proteins affect contraction are currently unknown. We have found that contractile stimulation induces the spatial reorientation of the intermediate filaments. Currently, we are using molecular, cellular, physiological, and biochemical approaches to evaluate the role of PAK, Rho kinase and other molecules in the regulation of the intermediate framework and to understand how the intermediate filaments may facilitate force development in smooth muscle. In addition, the actin cytoskeleton of smooth muscle cells undergoes dynamic changes in response to a variety of stresses. We are also interested in studying the functional consequences of the tyrosine kinase Abelsen tyrosine kinase (Abl) in vascular smooth muscle under physiological and hypertensive conditions. Abl has potential to mediate the actin lattice remodeling in smooth muscle cells. We are testing the hypothesis that the activation of Abl may initiate a signaling process mediating the reorganization of cytoskeletal actin lattice and force development. The adapter proteins CrkII and Crk-associated substrate (p130CAS) and actin-regulatory proteins profilin may be important components of the cascade. Abnormal function of Abl in hypertensive animal models may be associated with the pathological development of the disease. These studies will shed light on the cytoskeletal regulation of smooth muscle contractility under normal and abnormal conditions. Understanding these cellular processes may provide new targets for the development of more effective therapies to treat such diseases as asthma and hypertension. (For extended publication lists for Dr. Tang, please visit the site http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed)
References
- Anfinogenova Y, Wang R, Li Q-F, Spinelli AM and Tang DD. Abl silencing inhibits CAS mediated process and constriction in resistance arteries. Circ Res 101(4): 420-428, 2007.
- Li Q-F, Spinelli AM, Wang R. Anfinoginova Y, Singer, HA and Tang DD. Critical role of vimentin phosphorylation at Ser-56 by p21-activated kinase in vimentin cytoskeleton signaling. J Biol Chem. 281 (45): 34716-34724, 2006. ePub September 20, 2006
- Wang RP, Li Q-F, and Tang DD. Role of vimentin in smooth muscle force development. Am J Physiol Cell Physiol 291:C483-489, 2006
- Wang RP. Li Q-F, Anfinogenova Y. and Tang DD. Dissociate of Crk-associated substrate from the vimentin network is regulated by p21-activated kinase upon acetylcholine activation of airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 292(1): L240-L248, 2007. ePub September 22, 2006
- Tang, DD, Y Bai and SJ Gunst. Silencing of p21-activated kinase attenuates vimentin phosphorylation on ser-56 and reorientation of the vimentin network during stimulation of smooth muscle cells by 5-hydoxytryptamine. Biochem. J. 388: 773-783, 2005
