Kevin Mangum

Kevin Mangum

 

Kevin Mangum
Bachelor of Science in Biology from Davidson College, Davidson, NC


Dissertation Project: Mediators of smooth muscle cell dedifferentiation and regeneration in vascular disease


In addition to providing structural support and contractile regulation of blood vessels, smooth muscle cells (SMCs) have been implicated in various disease states. Specifically, by modulating the expression of several SMC-specific genes, SMCs are able to regain a more plastic phenotype, which involves loss of SMC-specific markers and increased proliferation and migration. Serum response factor (SRF), a regulator in SMC differentiation, binds to richly conserved CArG cis-elements at the majority of SMC promoters. Although clearly important for SMC differentiation, SRF it is also expressed in many other tissues and regulates cardiac as well as skeletal muscle gene expression. In contrast, myocardin, a SRF cofactor that regulates SMC as well as cardiac-specific gene expression, plays a key role in SMC-specific differentiation. Furthermore, the role of other transcription factors in the myocardin family, such as myocardin-related transcription factor-A (MRTF-A), however, are less understood. Although not much is known regarding MRTF-A’s role in regulation of SMC differentiation, it is believed that MRTF-A translocates to the nucleus in response to Rho-A signaling, an important trigger for SMC differentiation. However, the specific structural modification of MRTF-A involved in its nuclear transport remains unidentified.


After joining the MD/PhD program in 2011 and completing my first two years of medical school here at UNC, I rotated in two different labs studying vascular dynamics and pathogenesis. During my first rotation in Eleni Tzima’s lab, I studied differential changes in ribosomal biogenesis and inflammation post-myocardial infarction in response to “Compound B.” While a rotation student in Chris Mack’s lab, I studied the nuclear modification of MRTF-A and examined endothelial-10T communication and cellular organization using siRNA knockdown of LARG and P115.


Currently in the Christopher Mack Lab, I am identifying the structural modification of the nuclear form of MRTF-A to yield insight into this component of the SMC differentiation model. Additionally, using an endothelial cell and T10 cell model, I am exploring the role of two GEF proteins involved in Rho-A signaling, LARG and P115, in vascular structural organization. The goal of future projects will be to elucidate specific mediators of SMC dedifferentiation and regeneration that can be utilized as therapeutic targets in specific vascular diseases.


Click here for a list of publications from the Mack laboratory.

 

 

Current Graduate Students