Robert V. (Rob) Stahelin
Ph.D. in Chemistry in 2003 at the University of Illinois at Chicago.
Postdoctoral studies 2003-2006 at the University of Illinois at Chicago
Interdisciplinary research focused on biological membranes has revealed them as signaling and trafficking platforms for processes fundamental to life. Biomembranes harbor receptors, ion channels, lipid domains, lipid signals, and scaffolding complexes, which function to maintain cellular growth, metabolism, and homeostasis. Moreover, abnormalities in lipid metabolism attributed to genetic changes among other causes are often associated with diseases such as cancer, arthritis and diabetes. Thus, there is a need to comprehensively understand molecular events occurring within and on membranes as a means of grasping disease etiology and identifying viable targets for drug development.
A rapidly expanding field in the last decade has centered on understanding membrane recruitment of peripheral proteins. This class of proteins reversibly interacts with specific lipids in a spatial and temporal fashion in crucial biological processes. Typically, recruitment of peripheral proteins to the different cellular sites is mediated by one or more modular lipid-binding domains through specific lipid recognition. Structural, computational, and experimental studies of these lipid-binding domains have demonstrated how they specifically recognize their cognate lipids and achieve subcellular localization. However, the mechanisms by which these modular domains and their host proteins are recruited to and interact with various cell membranes often vary drastically due to differences in lipid affinity, specificity, penetration as well as protein-protein and intramolecular interactions.
As there is still a paucity of predictive data for peripheral protein function, these enzymes or structural proteins are often rigorously studied to characterize their lipid-dependent properties. Our research is targeted at identifying peripheral protein drug targets, designing predictive functions for this class of proteins, and understanding their biological mechanisms of activation as a means of creating better therapies.
1) Ebola virus and Marburg virus assembly and budding from the host cell plasma membrane.
2) Ceramide-1-phosphate and other sphingolipids signaling in cancers.
3) Zika virus and alteration of host cell lipid metabolism.
4) Disovery of new lipid-binding proteins.
NIH R01 AI081077 "Lipid-protein interactions in virus assembly and virus like particle formation"
NIH R21 AI121841 "A new system to modculate phosphatidylserine to investigate filovirus budding"
Pubmed search: https://www.ncbi.nlm.nih.gov/pubmed/?term=stahelin+rv
Wijesinghe, K.J., Urata, S., Bhattarai, N., Kooijman, E.E., Gerstman, B.S., Chapagain, P.P. Li, S., and Stahelin, R.V. “Detection of Lipid Induced Structural Changes of the Marburg Virus Matrix protein VP40 Using Hydrogen/Deuterium Exchange Mass Spectrometry” (2017) J. Biol. Chem. 292, 6108-6122.
Shirey, C.M., Ward, K.E., and Stahelin, R.V. “Notes and Tips for Improving Quality of Protein-Lipid Overlay Assays” (2017) Anal. Biochem. 516, 9-12.
Shirey, C.M., Ward, K.E., and Stahelin, R.V. “Investigation of the biophysical properties of a fluorescently modified ceramide-1-phosphate” (2016) Chem. Phys. Lipids 200: 32-41.
Wijesinghe, K.J. and Stahelin, R.V. “Investigation of the Lipid Binding Properties of the Marburg Virus Matrix Protein VP40” (2016) J. Virol., 90, 3074-3085.
Del Vecchio, K. and Stahelin, R.V. “Using Surface Plasmon Resonance to Quantitatively Assess Lipid-Protein Interactions. (2016) Methods Mol. Biol. 1376: 141-153.
Johnson, K.A., Taghon, G.J., Scott, J.L, and Stahelin, R.V. “The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress” (2016) Sci. Rep. 6:19125.
Oda, S., Noda, T., Wijesinghe, K.J., Halfmann, P., Bornholdt, Z.A., Abelson, D.M., Armbrust, T., Stahelin, R.V., Kawaoka, Y., Saphire, E.O. “Crystal structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-terminal Domain for Immunosuppression” (2016) J. Virol., 90, 1839-1848.
Adu-Gyamfi, E., Johnson, K.A., Fraser, M.E., Scott, J.L., Soni, S.P., Jones, K.R., Digman, M.A., Gratton, E., Tessier, C.R., and Stahelin, R.V. “Host cell plasma membrane phosphatidylserine regulates the assembly and budding of the Ebola virus” (2015) J. Virol. 89, 9440-9453.
Stahelin, R.V “Membrane binding and bending in Ebola VP40 assembly and egress“ (2014) Front. Microbiol., 5:300.
Stahelin, R.V., Scott, J.L., and Frick, C.T. “Cellular and molecular interactions of phosphoinositides and peripheral proteins” (2014) Chem. Phys. Lipids, 182, 3-18.
Adu-Gyamfi, E., Soni, S.P., Jee, C.S., Digman, M.A., Gratton, E., and Stahelin, R.V. “A loop in the N-terminal domain of Ebola virus VP40 is important in viral assembly, budding, and egress” (2014) Viruses, 6, 3837-3854.
Soni, S.P. and Stahelin, R.V. “The Ebola virus matrix protein VP40 selectively induces vesiculation from phosphatidylserine-enriched membranes” (2014) J. Biol. Chem. 289, 33590-33597.