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The Garcia Lab at New York Medical College

Compiled image of activities in the Garcia Lab at NYMC

The Garcia Laboratory is focused on the role of the vasoactive cytochrome P450 (CYP)-derived eicosanoid, 20-hydroxyeicosatetraenoic acid (20-HETE) and it’s recently identified high affinity G-protein coupled receptor (GCR), GPR75. Understanding the 20-HETE/GPR75 pairing and how GPR75 mutations exhibit altered or disrupted receptor signaling will shed light as to how to better target GPR75, laying the necessary foundation for the development of novel receptor blockers that have the potential to treat diseases such as chronic kidney disease, hypertension, heart failure and obesity; all of which are associated with elevations in 20-HETE.

Our lab is also focused on exploring the novel protein-protein interplay between endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) in endothelial cells. We identified PAI-1 as a potent intracellular negative regulator of eNOS, binding directly to eNOS and inhibiting nitric oxide (NO) production, a key mediator regulating vascular tone and inflammation. This new nonproteolytic role for PAI-1 wherein increases in endothelial derived PAI-1 contribute to the promotion of endothelial dysfunction is completely unexpected and highly interesting. In fact, it suggests that pharmacological targeting and antagonism of PAI-1 may be a valuable method to promote vascular homeostasis. Studies in our lab focus on identifying the precise region on PAI-1 that facilitates eNOS binding and characterize how pharmacological antagonism of PAI-1 can alter this interaction.

We are very interested in training young scientists at all levels (high-school, undergraduate, and graduate and postdoctoral fellows). If you are interested feel free to contact us with your cover letter and CV to Victor_Garcia@nymc.edu.

Collaborations

The labs of Victor Garcia, Ph.D., assistant professor of pharmacology, and Michal L. Schwartzman, Ph.D., professor and chair of the Department of Pharmacology, recently collaborated with Regeneron and discovered rare genetic mutations in the 20-HETE receptor (20HR), GPR75, associated with a protection against obesity in humans. These findings correlated with studies in mice (Control vs. Gpr75-/- (knockout)) exposed to high-fat diet which were conducted at New York Medical College. Ongoing studies and collaborative efforts between Regeneron and the Garcia/Schwartzman labs seek to explore this new and exciting discovery further.

To learn more check the video below: