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McNamara 

 

Coleen  A.  McNamara
Degree(s): M.D.
Graduate School: Medical College of Ohio
Primary Appointment: Associate Professor of Internal Medicine, Cardiovascular Medicine

Research Interests:
Role of Id3 and Id3a in Regulating the Smooth Muscle Cell Response to Vascular Injury Gene Delivery

Email Address: cam8c@virginia.edu
 
Biomedical Sciences Graduate Program(s)
  • Molecular Medicine


    • Research Description

    Current summary:
    Intimal smooth muscle cell (SMC) proliferation plays a key role in atherosclerosis and restenosis following vascular injury. Many extracellular growth factors liberated at the time of vascular injury are known to stimulate SMC proliferation, however the molecular mechanisms that regulate the expression of genes involved in cell cycle progression in SMC are poorly understood. Members of the helix-loop-helix (HLH) family of transcription factors are known to regulate growth in a variety of cell types. Recent data suggests that HLH factors regulate proliferation through effects on cell cycle regulatory factors. Our preliminary data suggests that the HLH factor Id3 is involved in the SMC proliferative response. Id3 is expressed in the developing neointima and overexpression of Id3 enhances SMC proliferation in culture. As Id is a dominant negative regulators of specific gene expression, it is likely that Id3 enhances SMC proliferation by inhibiting the expression of genes that favor cell cycle arrest. Indeed, our preliminary data demonstrates that Id3 blocks transcription of the cyclin dependent kinase inhibitor p21. Using the yeast two-hybrid system, we have recently cloned a novel isoform of Id3 called Id3a. The Id3a mRNA retains a coding intron, generating an Id3a protein with a unique carboxyl terminus. Interestingly, the C-terminus of Id3 is essential for its major function as a dominant negative regulator of specific gene expression suggesting that Id3a has unique function from Id3. Using in situ hybridization in the rat carotid injury model, we have shown that, in contrast to Id3, Id3a is not detected in normal medial SMC. Interestingly, Id3a is abundantly expressed in the SMC in the neointima 6, 14, and 28 days after vascular injury. Thus, studies in my laboratory are focused on determining the role of Id3 and Id3a in regulating the smooth muscle cell response to vascular injury.

    Dr. McNamara is also the Director of the Vascular Biology Training Grant. The program's website can be viewed at:

    Selected Publications

  • 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

  • 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, 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.

  • 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.

  • PubMed Listings for this Faculty Member

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    Contact Information

     

    Office Address:

    PO Box 801394, MR-5, G231, 

     

    Office Phone:

    +1 434-982-3366

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