McLendon receives AHA career development award

Jared McLendon, PhD, associate in the Division of Cardiovascular Medicine, has received a three-year, $231,000 American Heart Association (AHA) Career Development Award. In previous years, McLendon has earned an Alzheimer’s Association Research Foundation Award and an AHA postdoctoral fellowship award. With this new funding, McLendon will continue his work examining the Sorbs2 gene, which he had previously investigated as a protection against the onset of Alzheimer’s disease.

“The proposed research in this CDA,” McLendon said, “has significant potential to transform our knowledge of cytoskeletal remodeling processes in smooth muscle plasticity and blood pressure regulation via defining the functional role of Sorbs2 in vascular smooth muscle cells.”

Cardiovascular disease represents a leading cause of death worldwide affecting more than half of adults in the United States. Damaged and dysregulated vascular smooth muscle cells can contribute to the pathophysiological mechanisms (vascular remodeling, hypertension) of vascular diseases through increased proliferation, migration, and abnormal contraction. The molecular mechanisms that underlie these are not completely understood. Arterial walls are under a variety of mechanical stresses including transmural pressure, cyclic stress, interstitial flow, and in the case of neointimal injury, laminar or oscillating blood flow induced shear stress. Understanding the molecular mechanisms that sense and respond to these mechanical stressors may help to identify disease causing mechanisms that can become future therapeutic targets.

McLendon and his colleagues have identified Sorbs2 as a potential vascular disease associated gene that associates with mechanical signaling machinery and regulates cytoskeleton stability. “Our preliminary data shows that Sorbs2 is abundantly expressed in arteries, is downregulated in humans and animal models of vascular disease and is upregulated in vitro by smooth muscle cell differentiation and mechanical stretch.”

The researchers created smooth muscle-cell specific Sorbs2 knockout mice and found increased blood pressure, dysregulated contractile gene expression in arteries, and decreased smooth muscle cell proliferation in culture. “Our proposed experiments here will identify if Sorbs2 is regulated by mechanical stresses in smooth muscle. Then we will determine how Sorbs2 participates for mechanical signaling pathways in smooth muscle downstream of cell : cell and cell : matrix connections.”

“Support from the CDA program will significantly aid my career development goals within the next three years,” McLendon said. He cited gaining necessary training in vascular biology and mechanical signaling networks and to establish an independent research program. McClendon also said he is grateful for the support from mentors Ryan Boudreau, PhD; Isabella Grumbach, MD, PhD; and Kris Demali, PhD (Department of Biochemistry and Molecular Biology).

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