A. Wayne Orr, Ph.D.
Associate Professor, Department of Pathology and Translational Pathobiology and the Department of Cell Biology and Anatomy.
Assistant Director for Professional Development, Center for Cardiovascular Diseases and Sciences
Louisiana State University Health Sciences Center, Shreveport, LA
The laboratory currently has several ongoing projects centered on the role of vascular cell signaling in cardiovascular disease. During atherosclerosis, changes in the local microenvironment activate certain signaling pathways to modulate vascular cell phenotype, resulting in proinflammatory endothelial activation and the smooth muscle cell fibroproliferative response. We have a longstanding interest in the remodeling of the subendothelial matrix during atherosclerosis, having previously shown that matrix-specific signaling regulates endothelial cell activation in response to both hemodynamic shear stress and oxidized low density lipoproteins. We are currently examining the role of integrin affinity, integrin-specific signaling, and endothelial integrin signaling in vivo to characterize their role in atherosclerosis. Additionally, we have found that the Nck family of adaptor proteins critically regulate endothelial cell activation in response to shear and oxidant stress and are working to understand the mechanisms regulating Nck signaling during endothelial activation. Lastly, work from our group and others have found an important role for the Eph/ephrin family of guidance molecules in regulating inflammation and atherosclerosis, and we are currently examining the mechanisms by which Eph/ephrin signaling affects endothelial and smooth muscle cell function in atherosclerosis.
The laboratory was recently awarded an NIH R01 grant to fund our studies on the Nck adaptor proteins in cardiovascular disease and recently received a fundable score on a second R01 grant examining matrix-specific signaling in endothelial cell activation. As such, we are actively recruiting Research Associates, Post-doctoral Fellows and Graduate Students to join our group.
1. Yurdagul Jr. A., Sulzmaier F., Chen X.L., Pattillo C.B., Schlaepfer D.D., and A.W. Orr. (2016) Focal adhesion kinase activates RSK to drive NF-kB activation and endothelial proinflammatory gene expression by oxidized LDL. J. Cell Sci., 129: 1580-1591.
2. Yurdagul Jr. A. and A.W. Orr. (2016) Blood brothers: hemodynamics and cell-matrix interactions in endothelial function. In press at Antioxid. Red. Sig.
3. Yurdagul Jr. A., Finney A.C., Woolard M.D., and A.W. Orr. (2016) The Arterial Microenvironment: The Where and Why of Atherosclerosis. Biochem J., 473: 1281-1295.
4. Chen J.*, Green J.*, Yurdagul A. Jr., Albert P., McInnis, M.C., and A.W. Orr. (2015) avb3 integrins mediate flow-induced NF-kB activation, proinflammatory gene expression, and early atherogenic inflammation. Am. J. Pathol., 185: 2575-2589. * co-first authors.
5. Chen J., Leskov I., Yurdagul A. Jr., Thiel B., Kevil C.G., Stokes K.Y., and A.W. Orr. (2015) Recruitment of the adaptor protein Nck to PECAM-1 couples oxidant stress to canonical NF-kB signaling and inflammation. Sci. Signal. 8: ra20.
6. Navratil A.R., Vozenilek A.E., Cardelli J.A., Green J.M., Thomas M.J., Sorci-Thomas M.G., Orr A.W., and M. Woolard. (2015) Lipin-1 contributes to modified low-density lipoprotein-elicited macrophage pro-inflammatory responses. Atherosclerosis, 242: 424-432.
7. Yurdagul Jr. A., Green J., Albert P, McInnis M.C., Mazar A.P., and A.W. Orr. (2014) a5b1 integrin signaling mediates oxidized LDL-induced inflammation and early atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 34: 1362-1373.
8. Funk S.D., Yurdagul Jr. A., Albert P., Traylor J., Jin L., Chen J., and A.W. Orr. (2012) EphA2 activation promotes the endothelial cell inflammatory response: a potential role in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 32: 686-695.
Alexandra Finney, Graduate Student
Jonette Green, Graduate Student
Erin Langford, MD, Pathology Resident
Kimberly LeBlanc, Medical Student
James Bohn, Undergraduate Student
Brenna Pearson, Undergraduate Student
Brittini Coker, Undergraduate Student
Will Cooper, High School Student
Inside LSUHSC-S: Christopher Kevil, Matthew Woolard, Christopher Pattillo, Xinggui Shen, Shenuarin Bhuiyan, David Krzywanski, Kevin McCarthy, Manikandan Panchatcharam, Steven Alexander, Felicity Gavins, Karen Stokes.
Outside LSUHSC-S: Brian Petrich (Emory), William DeGrado (UCSF), Sanford Shattil (UCSD), Zhijian “James” Chen (UT Southwestern Medical Center), Richard Hynes (MIT), Louise Larose (McGill University), Horace DeLisser (Univ. of Pennsylvania), James Sowers (Univ. of Missouri), , John Tarbell (CUNY), Michael Autieri (Temple University), Nathaniel Gray (Harvard University), Jin Chen (Vanderbilt).