研究领域
Biochemistry
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 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. The below points highlight the different avenues of research in the Stahelin lab:
Molecular Basis of Viral Assembly. We are investigating how viruses such as the Ebola virus assembles at the plasma membrane of human cells to form the bud site for generation of a new viral particle. Funded by NIAID.
Discovery of New Lipid-Binding Domains. Integration of computational biology, bioinformatics, structural biology, biochemistry, biophysics, and cell biology to discover new lipid-binding domains in the human genome.
Lipid-Mediated Regulation of Proinflammatory Enzymes. We are elucidating the role of phosphoinositides and sphingolipids in the regulation of proinflammatory enzymes. Funded by the AHA.
近期论文
查看导师最新文章
(温馨提示:请注意重名现象,建议点开原文通过作者单位确认)
Stahelin, R.V. and Cho, W. "Membrane Binding Analysis of C1 and C2 Domains Using Surface Plasmon Resonance" (2001) Biophys. J., 80:1, 534a.
Bittova, L., Stahelin, R.V., and Cho, W. "Roles of Ionic Residues of the C1 Domain in Protein Kinase C-α Activation and the Origin of Phosphatidylserine Specificity" (2001) J. Biol. Chem., 276, 4218-4226.
Stahelin, R.V. and Cho, W. "Differential Roles of Ionic, Aliphatic, and Aromatic Residues in Membrane-Protein Interactions: A Surface Plasmon Resonance Study on Phospholipases A2" (2001) Biochemistry, 40, 4672-4678.
Stahelin, R.V. and Cho, W. "Roles of Ca2+ Ions in the Membrane Binding of C2 Domains" (2001) Biochem. J., 359, 679-685.
Stahelin, R.V., Long, F., Diraviyam, K., Bruzik, K.S., Murray, D., and Cho, W. "Phosphatidylinositol-3-Phosphate Induces the Membrane Penetration of the FYVE Domains of Vps27p and Hrs" (2002) J. Biol. Chem., 277, 26379-26388.
Karathanassis, D., Stahelin, R.V., Bravo, J., Perisic, O., Pacold, C.M., Cho, W., and Williams, R.L. "Binding of the PX Domain of p47phox to Phosphatidylinositol-3,4-bisphosphate and Phosphatidic Acid is Masked by and Intramolecular Interaction (2002) EMBO J., 21, 5057-5068.
Stahelin, R.V., Forslund, R.E., Wink, D.J., and Cho, W. "Devlopment of a Biochemistry Laboratory Course with a Project-Oriented Goal" (2003) Biochemistry and Molecular Biology Education, 31, 106-112.
Stahelin, R.V., Rafter, J.D., Das, S., and Cho, W. "A Molecular Basis for Differential Subcellular Localization of C2 Domains of Protein Kinase C-α and Cytosolic Phospholipase A2" (2003) J. Biol. Chem., 278, 12452-12460.
Diraviyam, K., Stahelin, R.V., Cho, W., and Murray, D. "Computer Modeling of the Membrane Interactions of FYVE Domains" (2003) J. Mol. Biol., 328, 721-736.
Stahelin, R.V., Burian, A., Murray, D., Bruzik, K.S., and Cho, W. "Membrane Binding Mechanisms of the NADPH Oxidase PX Domains" (2003) J. Biol. Chem., 278, 14469-14479.
Stahelin, R.V., Long, F., Peter, B.J., Murray, D., De Camilli, P., McMahon, H.T., and Cho, W. "Contrasting Membrane Interaction Mechanisms of AP180 and N-terminal Homology (ANTH) and Epsin N-terminal Homology (ENTH) Domains" (2003) J. Biol. Chem., 278, 28993-28999.
Ananthanarayanan, B., Stahelin, R.V., Digman, M.A., and Cho, W. "Activation Mechanisms of Conventional Protein Kinase C Isoforms are Determined by the Ligand Affinity and Conformational Flexibility of Their C1 Domains" (2003) J. Biol. Chem., 278, 46886-46894.
Malkova, S., Stahelin, R.V., Long, F., Pingali, S.V., Cho, W., and Schlossman, M.L. "X-ray Reflectivity Studies of cPLA2-C2 Domains Adsorbed onto Langmuir Monolayers of SOPC" (2004) Biophys. J., 86:1, 377a.
Stahelin, R.V., Digman, M.A., Medkova, M., Ananthanarayanan, B., Rafter, J.D., Melowic, H.R., and Cho, W. "Mechanism of Diacylglycerol-Induced Membrane Targeting and Activation of Protein Kinase Cδ" (2004) J. Biol. Chem., 279, 29501-29512.
Blatner, N.R., Stahelin, R.V., Diraviyam, K., Hawkins, P.T., Hong, W., Murray, D., and Cho, W. "The Molecular Basis of the Differential Subcellular Localization of FYVE Domains" (2004) J. Biol. Chem., 279, 53818-53827.
Stahelin, R.V., Ananthanarayanan, B., Blatner, N.R., Singh, S., Bruzik, K.S., Murray, D., and Cho, W. "Mechanism of Membrane Binding of the Phospholipase D1 PX Domain" (2004) J. Biol. Chem., 279, 54918-54926.
Subramanian, P., Stahelin, R.V., Szulc, Z., Bielawska, A., Cho, W., and Chalfant, C.E. "Ceramide-1-Phosphate Acts as a Positive Allosteric Activator of Cytosolic Phospholipase A2 and Enhances the Interaction of the Enzyme with Phosphatidylcholine" (2005) J. Biol. Chem., 280, 17601-17607.
Stahelin, R.V., Digman, M.A., Medkova, M., Ananthanarayanan, B., Melowic, H.R., Rafter, J.D., and Cho, W. "Diacylglycerol-Induced Membrane Targeting and Activation of Protein Kinase Cε: Mechanistic Differences Between PKCδ and ε" (2005) J. Biol. Chem., 280, 19784-19793.
Malkova, S., Long, F., Stahelin, R.V., Pingali, S.V., Murray, D., Cho, W., and Schlossman, M.L. "X-ray Reflectivity Studies of cPLA2-C2 Domains Determine its Depth of Penetration and Membrane Orientation" (2005) Biophys. J., 89, 1861-1873.
Stahelin, R.V., Wang, J., Blatner, N.R., Rafter, J.D., Murray, D., and Cho, W. "The Origin of C1 and C2 Domain Interactions of PKC-α In Vitro and In Vivo" (2005) J. Biol. Chem., 280, 36452-36463.