Evan Juan Rose Hills
Investigating the role of dengue virus nonstructural protein 1-induced NLRP3 inflammasome activation in dengue pathogenesis
With an estimated 105 million infections globally, dengue virus (DENV), the causative agent of dengue fever, places a severe burden upon global public health. Severe manifestations of dengue fever are characterized by leak of plasma from the vascular system; these symptoms can develop into hypovolemic shock and organ failure if left untreated. The Harris laboratory and others have discovered that DENV non-structural protein 1 (NS1) is critical to dengue pathogenesis and can directly trigger vascular leak. The exact mechanism of NS1-induced vascular leak is still unknown, but recent work has shown that the DENV NS1 can activate inflammasomes, an innate immune sensor within cells. Inflammasome activation causes the release of inflammatory mediators which can lead to the disruption of the endothelium. However, it is currently unknown how NS1 activates the inflammasome. My project will focus on investigating this mechanism and its importance in causing vascular leak. Thus, I aim to investigate the genetic and molecular determinants governing NS1-induced NLRP3 inflammasome activation. The discoveries from this work may reveal potential therapeutics for the treatment of severe dengue.
Message To Sponsor
To the Rose Hills Foundation, Thank you for the funding and support for my research opportunity this summer. This experience has allowed me to develop specialized research skills and gain a view into the world of academia. I’ve learned critical techniques for conducting in vivo and in vitro assays, as well as how to develop and troubleshoot experiments. I was enamored by the collaboration found within academia, as my co-workers and seniors constantly contributed to my understanding of my research and gave critical tips on how to improve my techniques or what to investigate going forwards. From the things I have learned from experience, I have been further inspired to pursue a career in the field of infectious diseases and public health.