|Coleen McNamara |
Office Phone: 434-243-9396
Office Address: MR5 G133
Messenger Mail: PO Box 801394
PubMed listings for Coleen McNamara
In recent years, obesity and diabetes have reached epidemic proportions. These diseases have many health consequences including stroke, heart attack and peripheral vascular disease. Common to all of these is atherosclerosis, which is the process by which lipids, cells and fibrous elements accumulate within the walls of arteries. Coordinated gene expression is essential to maintain normal vascular tissue structure and function and many transcription factors regulate these processes. Our lab has recently identified the transcription factor Id3 as a major regulator of atherosclerosis and obesity. Our research currently focuses on these two areas, each of which includes several exciting projects:
Project 1: Id3 regulation of immune cell responses in atherosclerosis.
A variety of immune cells influence the development of atherosclerosis, including macrophages, T cells and B cells. While the role of B lymphocytes in atherosclerosis is understudied, they are generally thought to play a protective role. Using animal models, our lab has demonstrated that Id3 regulates the homing of B cells to the vasculature and that the loss of Id3 results in increased plaque formation. In ongoing research, we are utilizing different molecular imaging modalities to further explore and quantify the trafficking of radio-labeled cells to the vessel wall using intravital confocal microscopy, microSPECT/CT, and real-time imaging of cellular trafficking using a gamma camera. In addition, we hope to further elucidate the mechanism by which Id3 affects the function of these cells in disease.
Project 2: Id3 regulation of matrix formation and vascular remodeling.
Restenosis after stent deployment in atherosclerotic arteries is characterized by neointimal formation. Vascular smooth muscle cell migration, growth and matrix production are critical processes in atherosclerosis and restenosis. Our lab has previously demonstrated that Id3 is involved in vascular smooth muscle cell growth. Our data also indicates that Id3 plays a role in regulating extracellular matrix formation and matrix metalloproteinases, the enzymes that remodel matrix and facilitate cell migration. Using transgenic and knockout mice, and molecular and cellular biology techniques, our lab is currently investigating how Id3 regulates matrix protein production, and its remodeling by select matrix metalloproteinase enzymes.
Project 3: Id3 SNPs are associated with atherosclerosis.
Through strong collaborations with the UVA Center for Public Health Genomics, our lab is studying several SNPs that have been associated with various markers of atherosclerosis in diabetic and atherosclerotic populations. In ongoing research, we are determining the mechanism by which these SNPs alter Id3 function in order to understand how they might influence disease progression.
Project 4: Id3 regulation of adipose distribution and adipocyte function.
Studies from our lab have shown an important role for Id3 in the regulation of visceral adiposity in the mouse model. We have also demonstrated the role of Id3 in the transcriptional regulation of adiponectin (an anti-inflammatory cytokine produced by adipocytes). Further studies are underway to investigate the role of Id3 in the proliferation and differentiation of adipocytes and the role of Id3 in adipocyte function.
Forrest ST, Taylor AM, Sarembock IJ, Perlegas D, McNamara CA. Related Articles, Links Phosphorylation regulates Id3 function in vascular smooth muscle cells. Circ Res. 2004 Sep 17;95(6):557-9. Epub 2004 Aug 19. PMID: 15321928
Matsumura ME, Lobe DR, McNamara CA.Contribution of the helix-loop-helix factor Id2 to regulation of vascular smooth muscle cell proliferation. J Biol Chem. 2002 Mar 1;277(9):7293-7. Epub 2001 Nov 08.
Matsumura ME, Li F, Berthoux L, Wei B, Lobe DR, Jeon C, Hammarskjold ML, McNamara CA. Related Articles, Links Vascular injury induces posttranscriptional regulation of the Id3 gene: cloning of a novel Id3 isoform expressed during vascular lesion formation in rat and human atherosclerosis. Arterioscler Thromb Vasc Biol. 2001 May;21(5):752-8. Erratum in: Arterioscler Thromb Vasc Biol 2001 Aug;21(8):1384.
Forrest ST, Barringhaus KG, Perlegas D, Hammarskjold ML, McNamara CA. Related Articles, Links Intron retention generates a novel Id3 isoform that inhibits vascular lesion formation. J Biol Chem. 2004 Jul 30;279(31):32897-903. Epub 2004 May 24. PMID: 15159391