Robert Stahelin: 'Lipid-dependent Assembly and Budding of Emerging Viral Pathogens'

Robert Stahelin, the Retter Professor of Pharmacy and professor of medicinal chemistry and molecular pharmacology, discussed “Lipid-dependent Assembly and Budding of Emerging Viral Pathogens” at the Westwood Lecture Series on Feb. 23, 2023.

Abstract. Lipid-enveloped viruses include dangerous pathogens such as coronaviruses (e.g., SARS-CoV-2), filoviruses (Ebola virus and Marburg virus) and paramyxoviruses (Measles virus, Nipah virus, etc.). These viruses replicate and spread from the human cells they infect. Despite understanding some of the basics of how these viruses cause disease and enter cells, not much is known on how these dangerous pathogens interact with host cell lipids to acquire their lipid coat. The viral proteins regulate assembly and budding from the host cell membrane, using our own cell lipid membranes against us. This presentation will detail the basis of how these emerging pathogens hijack human cell components to form new virus particles that can spread from cell to cell or patient to patient.  The talk will also highlight strategies to potentially halt virus spread using small molecule strategies.

Bio. Stahelin began his research training during his undergraduate research while completing a B.S. in biochemistry at the University of Illinois at Chicago. This helped lead him to pursue a Ph.D. in chemistry at the University of Illinois at Chicago, which was completed in 2003. His research training and independent career has investigated the fundamental basis of how pharmacologically important peripheral proteins interact with lipids. In the late 1990s and early 2000s, new bioinformatics and structural data was providing a wealth of information on lipid binding proteins and particularly small, conserved modules (lipid-binding domains) that interacted with lipids such as phosphoinositides. However, biochemical and biophysical data lagged on the principles of how these proteins interacted with lipids embedded in bilayer membranes. Stahelin’s lab’s work brought new techniques to bear on the projects (such as surface plasmon resonance) and provided important insight into how the composite of electrostatic, hydrophobic, and aromatic residue interactions regulated both specific lipid head group binding and background bilayer interactions. This work has also provided a better fundamental understanding of how the composite of interactions regulated subcellular localization and the spatial and temporal dynamics of these proteins involved in several diseases. Understanding these interactions has been instrumental in determining pharmacological strategies to inhibit lipid-protein interactions.

Stahelin started his lab in 2006 with an assistant professor position at the Indiana University School of Medicine-South Bend and the University of Notre Dame. He was promoted to associate professor in 2012 and named an IUSM Showalter and Navari Family Scholar in 2014. In 2017, he moved his lab to the Department of Medicinal Chemistry and Molecular Pharmacology at Purdue University. His lab’s findings have also been critical to understanding replication of viruses with high fatality rates such as Ebola virus and SARS-CoV-2. The viral matrix protein, which regulates assembly and budding of these lipid-enveloped viruses from the host cell they infect, has been a major focus. This work has demonstrated dynamics of viral matrix protein oligomerization and assembly in live cells, as well as how the viral proteins regulate membrane curvature changes to form the viral lipid envelope. This work has had a significant impact in understanding how one viral protein regulates the complex biochemical and biophysical mechanisms that regulate formation of a lipid-envelope and designed strategies to inhibit these processes. The work of Stahelin’s lab has been well-recognized over the last several years, including invited reviews on lipid binding proteins and viral assembly at the lipid interface. In 2022, Stahelin was named a fellow of the American Society for Biochemistry and Molecular Biology.