The destructive effects of acute and chronic inflammation on the cardiovascular system are omnipresent in my clinical cardiology and medicine attending services. Currently, my laboratory seeks to understand the molecular mechanisms that control vascular stability and the pathways by which…
more inflammatory cytokines disrupt such pathways. This work was informed by my studies investigating the pathophysiology of human vascular dysplasias (supravalvular aortic stenosis, hereditary hemorrhagic telangiectasia, and cerebral cavernous malformations) and experiments exploring the role of neural guidance cues, such as Slit and Netrin, on the endothelium. Recently, we found that inflammatory cytokines have immediate, direct, and disruptive effects on cellular barrier that is mediated by a pathway that is distinct from canonical transcription cascades such as NF-κB. We find that the ARF family of small GTPase destabilizes endothelial junctional structures including cadherin-catenin complexes in response to multiple cytokines. Our discoveries indicate that blunting this cytokine receptor-ARF-cadherin pathway offers a strategy for blunting the destructive effects of inflammatory cytokines without incurring broad immunosuppression inherent in current anti-cytokine therapies. We have extended these studies to find that strikingly similar signaling pathways may explain how cancer cells metastasize. We are exploring these mechanisms in more depth by using genetic and chemical biology approaches. During the course of my career, my science has opened opportunities for me to serve as founding chief scientific officers of two start-up biotechnology companies, Hydra Biosciences (Boston) and Navigen (Salt Lake City). This industry experience along with my academic roles in clinical medicine and in science prepared me for my current administrative roles as Associate Vice President for Research and Chief Scientific Officer for University of Utah Health Sciences, and Vice Dean for Research for the School of Medicine. As Vice Dean, I am responsible for overseeing the research enterprise, including development and realization of a strategic plan in each of our academic departments. As Associate Vice President and CSO, I am charged with coordinating and maximizing the University healthcare system’s investment in translational, clinical, and healthcare research that must sustain, grow, differentiate, and distinguish our healthcare delivery and our academic operations. This broad experience has guided my own academic pursuits and my institutional aspirations as I seek to advance science and translate discoveries into clinical applications and better healthcare and value for patients.
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