INDIVIDUAL RESEARCHER
Dale D. Tang
, M.D.
, Ph.D.
Professor
e-mail:
tangd@mail.amc.edu
Education
-
Ph.D. from
Tonji Medical University, Wuhan, China
-
M.D. from
Tonji Medical University, Wuhan, China
Current Research
View the Cytoarchitecture of Smooth Muscle Cells
Our laboratory is focusing on smooth muscle biology and pathology. Our first research project is to understand how smooth muscle contraction is regulated. In addition to myosin activation, the actin cytoskeleton undergoes reorganization in airway smooth muscle (a key regulator of airway tone) in response to contractile stimulation. The dynamic changes in the actin cytoskeleton may enable smooth muscle cells to adjust their structure and contractility in response to alterations in environments surrounding them. We propose that myosin activation may serve as the “engine” for smooth muscle contraction whereas remodeling of the actin cytoskeleton including actin polymerization may function as the “transmission system” in smooth muscle. However, the cellular and molecular mechanisms that regulate the dynamic actin cytoskeleton are not well understood. We have recently found that Abi and GMF are highly expressed in airway smooth muscle. We will characterize the physiological role of Abi and GMF in the regulation of actin polymerization in airway smooth muscle. To accomplish the goal, several novel approaches such as a new technology to manipulate gene expression in smooth muscle tissues, cell-permeable peptides, the sensitive biochemical assay, and confocal fluorescent microscopy will be utilized.
Our second research project is to understand the pathogenesis of asthma, which is a serious pulmonary disease that is characterized by airway hyperresponsiveness (AHR) and airway remodeling. Previous studies show that contraction of airway smooth muscle plays a critical role in mediating AHR whereas proliferation of airway smooth muscle cells largely contributes to the pathogenesis of airway remodeling. Currently, we attempt to characterize the role of Abi and Abl tyrosine kinase in the regulation of smooth muscle contraction and cell proliferation in vitro by using the state-of-art technology. More importantly, we are using Cre-flox technology to generate conditional knockout mice and assess the role of these proteins in allergen-induced asthma. Completion of these studies should advance our knowledge regarding smooth muscle contraction/growth and asthma pathology. Obtaining this knowledge may identify new biological targets for the development of new therapy to treat asthma.
Research Interests
Cytoskeletal regulation of smooth muscle functions, pathogenesis of asthma and hypertension
References
- 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
- 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.
- Tang, DD. Invited Review: Intermediate filaments in smooth muscle. Am J Physiol Cell: 294:C869-C878, 2008
- Li, Q.F and Tang, DD. Role of p47(phox) in regulating Cdc42GAP, vimentin, and contraction in smooth muscle cells. Am J Physiol Cell Physiology, ePub, 10/7/2009, 297: C1424-C1433, 2009
- Jia L and Tang, DD. Abl activation regulates the dissociation of CAS from cytoskeletal vimentin by affecting CAS phosphorylaiton in smooth muscle. Am J Physiol Cell Physiology, 299: C630-637, 2010 (ePub, 7/7/2010)
- Jia L, Wang RP and Tang, DD. Abl regulates smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 activation