Professor Emeritus
Department of Physiology
University of South Alabama
College of Medicine
MSB 3074
Mobile, AL 36688
E-mail: tlincoln@southalabama.edu

Mailing Address:
Department of Physiology
Room 3092 Medical Sciences Building
University of South Alabama
College of Medicine
Mobile, Alabama 36688

Phone: 251-460-6428
FAX: 251-460-6967

Ph.D., University of Tennessee, Knoxville
Postdoctoral Studies: Vanderbilt University

Research Interests:

Our laboratory is interested in the role of nitric oxide (NO) signaling and the mechanisms by which the second messenger, cyclic GMP, regulates vascular smooth muscle cell function. NO increases cyclic GMP that, in turn, activates a serine/threonine protein kinase, the cyclic GMP-dependent protein kinase (PKG).   We have identified several proteins whose phosphorylation is catalyzed by PKG in smooth muscle cells. More recently, we have found that NO and PKG regulate gene expression in vascular smooth muscle cells. Stable transfection or adenoviral gene delivery of the Type I PKG gene into vascular smooth muscle cells induces the expression of contractile proteins such as smooth muscle specific myosin and actin and repress the expression of extracellular matrix proteins such as osteopontin. DNA microarray analysis shows that over 100 genes appear to be regulated by PKG in smooth muscle. These results are pathophysiologically important because arterial vascular smooth muscle cells, in response to injury and atherosclerosis, lose their contractile phenotype and secrete extracellular matrix proteins. Hence, PKG appears to suppress the development of the atherosclerotic phenotype in vascular smooth muscle cells. More recently, we have observed that in response to injury and inflammatory cytokines, endogenous PKG mRNA expression is suppressed resulting in the loss of PKG protein in the vascular smooth muscle cells. These inflammatory conditions promote the modulation of vascular smooth muscle cells to the atherosclerotic phenotype. Restoration of PKG expression by adenoviral gene transfer restores the contractile, non-atherosclerotic phenotype. Therefore, one possible link between inflammation and fibroproliferative behavior of vascular smooth muscle cells in the suppression of PKG expression. We are currently studying the molecular mechanisms that control PKG mRNA and protein expression in vascular smooth muscle cells and would like to identify pharmacologic agents that increase PKG expression in these cells to prevent the modulation to the atherosclerotic phenotype. Clearly, adenoviral gene transfer of PKG cDNA into vascular lesions in vivo would be one mechanism using gene therapy for such vascular diseases as atherosclerosis, restenosis and inflammatory lesions.

Recent Publications:

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