Gary L. Sanford, Ph.D.
Associate Professor, Department of Biochemistry
Morehouse School of Medicine
B.A., Miles College , 1972
Ph.D., Brown University , 1978
Email: gsanford@msm.edu
Office Phone: (404) 752-1504
Department: (404) 752-1501
Fax: (404) 752-1772

Research Interests

Vascular remodeling is a prime contributor to the pathogenesis of a number of clinical disorders, including hypertension, atherosclerosis and restenosis. The remodeling process is a complex set of events involving endothelial cell injury and/or dysfunction that result in intimal/medial thickening. Although this area has received significant attention, the cellular and molecular mechanisms of vascular remodeling are not completely understood. Our studies have shown that endothelial cell cultures are made dysfunctional by injury-release factors that stimulate vascular smooth muscle cell growth and migration, which are modulated by extracellular matrices. Integrated studies are still needed to understand how these mediators are involved in the remodeling process. Co-culture of vascular cells with three-dimensional architecture provides a unique opportunity to conduct such integrated studies. The high aspect ratio vessel (HARV) and the slow turning lateral vessel (STLV) rotating bioreactors produce extremely low fluid shear, high oxygenation of cultures and high mass transfer. These properties allow cells to grow in three-dimensional tissue-like constructs. Earlier co-culture models (e.g., transwell co-cultures) did not have the cell: matrix or cell: cell interactions of a three-dimensional model. The results to date indicate that questions that relate to the mechanism of hemodynamic-induced vascular remodeling, the importance of cell: cell and cell: matrix interactions in this process, or the initial signal transduction and/or mechanotransduction mechanisms remain unanswered. The long term goal of this research area is to provide a better understanding of the sequence of events (and signaling) involved in the early period of vascular remodeling.

Ongoing research in my laboratory also includes studies examining the mechanism(s) by which cells respond to changes in gravity, e.g., hypergravity or ground-based models of microgravity. The goal of one of these projects is to provide an understanding of the impact of gravity on wound healing. The objectives of the research are to: 1) evaluate whether changes in vascular cell proliferation and migration induced by different gravitational fields are coupled to the expression of autocrine growth and migration factors; 2) assess whether simulated microgravity and/or hypergravity alter the expression of these autocrine growth and migration factors; 3) investigate possible signal transduction mechanisms that may be involved in gravity induced cellular changes. A second project investigates the possibility of using microgravity-based rotating bioreactors in engineering three-dimensional vascular tissues.

Relevant Publications

Dutt, K. , Sanford, G., Harris-Hooker, S., Brako, L., Kumar, R., Sroufe, A., and Melhado, C. Three-dimensional model of angiogenesis: Co-culture of human retinal cells with bovine aortic endothelial cells in the NASA bioreactor. Tissue Engineering 2003; 9:893-908.

Sanford, G.L. , Ellerson, D., Melhado-Gardner, C., Sroufe, A.E., and Harris-Hooker, S. Three-dimensional growth of endothelial cells in the microgravity-based rotating wall vessel bioreactor. In Vitro Cellular & Developmental Biology-Animal 2002; 38:493-504.

Sanford , G.L. , Harris-Hooker, S., Lui, J., Melhado-Gardner, C., Pink, Y., Wallace, T., and Bosah, F.N. Influence of changes in gravity on the response of lung and vascular cells to ischemia/reperfusion in vitro. Journal Gravitational Physiology 1999; 6:27-28.

Sanford , G.L. , Harris-Hooker, S., Lui, J., and Bosah, F.N. Wound healing following injury to vascular smooth muscle cell cultures is modulated by culture under hypergravity. Journal Gravitational Physiology 1999; 6:29-30.

Keywords

Wound healing, Ischemia injury, Lung, Vascular cell biology