GDCB Promising Scientist Research Series

Speaker: Dr. Olivia Molinar-Inglis, UC President’s Postdoctoral Fellow in the Department of Pharmacology at the University of California, San Diego in Dr. JoAnn Trejo’s Laboratory

Title: "APC-PAR1 confers anti-apoptotic protection through the β-arrestin-2-Sphk1-S1PR1-Akt axis in endothelial cells"

Abstract: Dr. Olivia Molinar-Inglis earned her bachelor of science in microbiology from The University of Texas at El Paso and a Ph.D. in developmental and cellular biology from Carnegie Mellon University. She is a former NIH/NIGMS-funded Institutional Research and Academic Career Development Award (IRACDA) Postdoctoral Scholar and a current UC President’s Postdoctoral Fellow in the Department of Pharmacology at the University of California, San Diego, in Dr. JoAnn Trejo’s Laboratory.

The Trejo Lab is focused on understanding the role of G-protein-coupled receptors (GPCRs) in vascular endothelial cells, a thin monolayer of semi-permeable cells that line blood vessels. G protein-coupled receptors (GPCRs) promote vascular dysfunction and inflammation. Endothelial dysfunction is counteracted by activated protein C (APC) activation of the GPCR, protease-activated receptor-1 (PAR1) to promote several anti-inflammatory endothelial cytoprotective processes such as endothelial barrier integrity and cell survival. APC-PAR1 requires the function of the S1PR1 effector in vascular endothelial barrier integrity but whether and how S1PR1 integrates to support vascular cell survival is not known. Our work demonstrates that PAR1 and S1PR1 co-associate in a caveolin dependent manner. Using a combined pharmacological and siRNA approach in endothelial cells, we demonstrate that APC/PAR1 is necessary to confer protection against TNF-α-induced apoptosis via the β-arr2-Sphk1-S1PR1-Akt signaling axis. Furthermore, we demonstrate that APC modulates the phosphorylation, translocation and activity of Sphk1 by β-arr2. In summary, transactivation of S1PR1 in vascular endothelial Akt-mediated cell survival is mediated by APC-PAR1-β-arr2 activation of Sphk1.

In addition to her research interests in GPCR-mediated endothelial barrier integrity, she is a very passionate educator with a strong background in facilitating the implementation of programs and initiatives aimed at increasing, supporting, and retaining a faculty, staff, and student body that is diverse at UCSD, San Diego State University and San Diego City College. In brief, Dr. Molinar-Inglis is actively involved in science outreach as the founder of STEM-ming for Success at UCSD, co-founding advisor for the UCSD Society for the Advancement of Chicanos/Hispanics, and Native Americans in Science and board member of the Better Education for Women in Science and Engineering (BE WiSE) at the San Diego Fleet Science Center. 

Meeting link: https://iastate.webex.com/iastate/j.php?MTID=m1b1629 afc82e9902a63cc1d469fef3cb

Questions? Contact Clark Coffman at ccoffman@iastate.edu.