A. Wayne Orr, PhD, received a five-year $2,876,200 R01 grant from the NIH National Heart, Lung, and Blood Institute for his project, "EphA2 regulation of atherosclerotic smooth muscle phenotype." 

Brenna Pearson-Gallion received the Second Place Poster in the Graduate Student category at the Feist Cardiovascular Research Symposium for her poster entitled: Altered EphA2 signaling in Nonalcoholic Fatty Liver Disease Progression”.

Dr. Syrine Ben Dhaou received the Second Place Poster award in the Postdoctoral Fellow category at the Feist Cardiovascular Research Symposium for her poster entitled: “Targeting endothelial Nck1 reduces atherosclerosis”.

Dr. Matthew Scott received the First Place Poster award at the Gordon Research Conference: Vascular Biology in Ventura, California for his poster entitled: The Role of EphA2 in Vascular Smooth Cell Proliferation, Migration, and Mitogenic Signaling.  (View Poster)

Brenna Pearson-Gallion was recently awarded a NIDDK F31 Predoctoral Fellowship award to fund her research on “EphA2 in Nonalcoholic Fatty Liver Disease.”

Dr. Wayne Orr and Dr. Karen Stokes were recently awarded an NIH T32 grant to establish a program for Multidisciplinary Training in Cardiovascular Pathophysiology (MTCP). The MTCP program is the only T32 training program in the state of Louisiana focused on cardiovascular disease.

Working with Dr. Andrew Yurochko, Dr. Orr organized the LSU Health Shreveport Faculty Development Workshops, a series of lectures aimed at assisting new faculty with starting a biomedical research laboratory.

Dr. Orr was appointed as an inaugural Charter Member to the new Atherosclerosis and Vascular Inflammation (AVI) study section. In addition, Dr. Orr was appointed to the ATVB Irvine H. Page Award Committee, the ATVB Leadership Committee, the NAVBO Meritorious Awards Committee, and the Editorial Board of Arteriosclerosis, Thrombosis, and Vascular Biology. Dr. Orr also serves as an Associate Editor for the American Journal of Pathology.

Dr. Mabruka Alfaidi was appointed to the NAVBO Membership Committee in September 2018, the ATVB Early Career Committee in July 2020, and the ATVB Early Career Editorial Board in January 20201.

Dr. Mabruka Alfaidi won the British Atherosclerosis Society Young Investigator Award in August, 2020. Additionally, Mabruka was a finalist for the 2020 ATVB Elaine Raines Young Investigator Award. Congratulations Mabruka!!

Work by Dr. Mabruka Alfaidi and others discussing the isoform-specific role of Nck1 in atherosclerotic endothelial activation was published in the Journal of Clinical Investigation.

Dr. Mabruka Alfaidi and Dr. Matthew Scott both received American Heart Association Post-doctoral Fellowships in January 2020. Congrats Mabruka and Matt!!

In May 2019, Dr. Alexandra Finney received the Chancellor’s Award which acknowledges the top outgoing PhD student for that school year. Dr. Finney’s dissertation work focused on “EphA2 regulates synthetic vascular smooth muscle fibroproliferative remodeling in experimental atherosclerosis” in November 2018. Congratulations Dr. Finney.

Zaki Al Yafeai received an American Heart Association Predoctoral Fellowship titled “Integrin affinity modulation in endothelial activation and atherosclerosis” in January 2019. Congratulations Zaki!

The Orr lab was awarded an NIH R01 grant in December 2018 to continue their work on the role of EphA2 signaling in atherosclerotic fibroproliferative remodeling.  

Dr. Alexandra Finney successfully defended her dissertation titled “EphA2 regulates synthetic vascular smooth muscle fibroproliferative remodeling in experimental atherosclerosis” in November 2018.  Congratulations Dr. Finney.

As part of the new COBRE Center for Redox Biology and Cardiovascular Disease, Dr. Orr will run a Redox Molecular Signaling core providing services for molecular biology, cell culture models, and analytical redox measurements.

The Orr lab was awarded an NIH R01 grant renewal in December 2016 to continue their work on the role of endothelial cell integrin signaling in atherosclerotic plaque formation.  

The Orr lab was awarded an NIH R01 award in July 2016 to study the role of Nck adaptor protein signaling in endothelial cell activation during atherosclerotic plaque development.  

Despite advances in treatments over the past several decades, cardiovascular disease remains the leading cause of death in developed countries worldwide. Atherosclerosis, a chronic inflammatory disease of the vessel wall, is responsible for more than 80% of all cardiovascular disease related deaths. Current models suggest that the local accumulation of low density lipoproteins (LDL, "bad cholesterol") in the vessel wall promotes an inflammatory response characterized by endothelial cell activation and leukocyte recruitment.  This early inflammatory response stimulates phenotypic changes in the underlying medial smooth muscle cells resulting in their proliferation and migration into the growing plaque, where they contribute both to plaque size and plaque stability.  Our lab studies how the arterial microenvironment, including soluble factors, vascular mechanics (stiffness, hemodynamics), and adhesive interaction, affects vascular cell function during atherosclerotic plaque formation. While current cardiovascular disease therapies target the systemic soluble risk factors, no therapeutics target the altered arterial microenvironment during atherosclerosis.  Through a better understanding of the molecular mechanisms regulating vascular cell function, we hope to identify novel therapeutic targets to limit cardiovascular disease. 

The subendothelial matrix in endothelial activation - Our research has shown an important role for matrix composition in modulating the cellular response to multiple atherogenic stimuli. Early during atherogenesis in vivo, wound-associated transitional matrix proteins (ex. fibronectin, fibrinogen) become deposited into the endothelial cell basement membrane. In vitro, these transitional matrix proteins enhance the ability of atherogenic stimuli, such as disturbed flow patterns and oxidized LDL, induce endothelial cell dysfunction, while components of the basement membrane (ex. collagen, laminin) limit endothelial cell dysfunction. We hypothesize that signals from cell-matrix interactions serve as a form of tissue memory, helping cells place atherogenic stimuli into a temporal context by indicating whether the tissue is actively remodeling.  Our current research seeks to understand the factors regulating matrix remodeling during atherogenesis (ex. hyperglycemia, oxidized LDL), to characterize how specific integrins (cell matrix receptors) contribute to endothelial activation in vitro and in vivo, and to characterize how integrin affinity modulation affects atherogenic endothelial activation.  

Nck adaptor proteins in atherogenic endothelial activation.  Work from our laboratory has shown that the Nck family of signaling adaptor proteins, Nck1 and Nck2, contribute to endothelial dysfunction under atherosclerotic conditions.  In response to shear or oxidant stress, Nck1/2 are recruited to tyrosine phosphorylated proteins at sites of cell-cell and cell-matrix adhesion, where they form specific signaling complexes to drive endothelial proinflammatory gene expression and vascular permeability.  Work from our group is currently characterizing the mechanisms regulating Nck1/2 recruitment following shear and oxidant stress and the role of individual Nck isoforms in endothelial activation in vitro and in vivo.   

Guidance Molecules in Atherogenic Remodeling - The ephrin and Eph family of cell-cell adhesion molecules are well characterized regulators of vascular and neuronal development and are implicated in numerous tissue remodeling responses in adult organisms. The Eph receptor EphA2 shows prominent expression in endothelial cells, macrophages, and synthetic smooth muscle cells, and we have demonstrated enhanced expression of EphA2 and its receptor ephrinA1 in both mouse models of atherosclerosis and human atherosclerotic plaques.  In endothelial cells, EphA2 signaling promotes proinflammatory endothelial activation, and EphA2 knockout mice show smaller plaques with reduced leukocyte recruitment.  However, EphA2 also contributes to smooth muscle growth, proliferation and extracellular matrix deposition, and plaques from EphA2 knockout mice show reduced markers of plaque stability.  Our current research seeks to characterize the dynamic interplay between smooth muscle EphA2 expression and matrix composition, determine the mechanisms by which EphA2 signaling affects smooth muscle proliferation and migration, and assess the role of EphA2 cell type-specific expression and signaling in atherosclerotic fibroproliferative remodeling..