加州北岭硕士名师团队

Raviner Abrol EDUCATION Ph.D. (Chemistry), California Institute of Technology, Pasaena, CA M.Sc. (Chemistry), Inian Institute of Technology, Kanpur, Inia B.Sc. Honours (Chemistry), University of Delhi, Inia POSTDOCTORAL APPOINTMENT IBM Thomas J. Watson Research Center, NY California Institute of Technology, CA COURSES TAUGHT Chemistry 461L, Biochemistry I Laboratory Chemistry 462L, Biochemistry II laboratory Chemistry 464, Principles of Biochemistry RESEARCH INTERESTS Computational Biochemistry an Biophysics Dr. Ravi Abrol’s research lab is focuse on eveloping an using computational methos to probe how protein structure an biochemical (protein-ligan an protein-protein) interactions of G protein-couple receptors (GPCRs) etermine cellular signaling an physiology, as well as how this knowlege can be use for the rational esign of rugs targeting GPCR signaling pathways. GPCRs are integral membrane proteins that form the largest superfamily in the human genome. The activation of these receptors by a variety of bioactive molecules regulates key physiological processes (e.g., neurotransmission, cellular metabolism, secretion, cell growth, immunity, ifferentiation), through a balance of G protein-couple an beta-arrestin-couple signaling pathways. This has mae them targets for ~50% rugs in the clinic. A molecular an structural unerstaning of these GPCR signaling pathways will have a broa impact on our unerstaning of cellular signaling an on rug iscovery efforts targeting GPCRs. Research in the Abrol Lab lies at the interface of Chemistry an Biology, where they are using computational biophysics an structural bioinformatics base methos to gain mechanistic insights into the biochemistry of GPCR signaling. The research is following three major themes to connect the sequence, structure, an signaling of GPCRs: Theme 1: From Structure to Signaling - How o GPCRs behave as allosteric machines an exhibit biase signaling? There are many challenges in experimental approaches to navigate the multiple conformations of GPCRs that can escribe their pleiotropic function. The Abrol Lab is eveloping the next generation of computational methos to escribe the conformational space available to GPCRs (especially the high-energy functionally important conformations) an to preict their effects on intracellular signaling. Theme 2: From Sequence to Structure - How o GPCRs fol in the membrane? There are several examples of isease-associate single point mutations in GPCRs, in which the mutant GPCR is not stable enough to escape the quality control of enoplasmic reticulum, but can be rescue by pharmacological chaperones to reach its final membrane estination. These partially stable receptor single-point mutants require looking at the thermoynamics of how they insert an fol in the membrane to gain a mechanistic insight into their instability. The Abrol Lab is eveloping methos to probe how small alpha-helical membrane proteins get inserte into the lipi bilayers by the Sec61 translocon machinery, to eventually unerstan this process for GPCRs. Theme 3: From Sequence to Signaling - How o GPCR sequence variations (receptor paralogs or mutations) lea to observe signaling an isease? Sequences contain a wealth of functional information, which has le to the evelopment of many computational approaches to extract this information. The Abrol Lab is eveloping structural bioinformatics tools that combine evolutionary methos using closely-relate paralog an ortholog sequences with their structural an functional information to unerstan the role of specific resiues an structural motifs in the functional ivergence of GPCRs. Stuents from Chemistry, Biochemistry, Biology, Physics, Math, an Computer Science will fin highly multi-isciplinary research opportunities in the Abrol Lab, aime at eveloping computational methos or applying existing methos or eveloping an applying new methos to unerstan the molecular mechanisms behin cellular signaling. Prior experience with computer programming is not necessary, however, stuents shoul be open to learning some programming as part of the research. There will also be joint research opportunities combining structural moeling of proteins with biochemical an biophysical experiments. REPRESENTATIVE PUBLICATIONS 1. “Ientifying multiple active conformations in the G protein-couple receptor activation lanscape using computational methos”; Dong S, Goar WA 3r, Abrol R (2017), G Protein Couple Receptors Part A (Methos in Cell Biology Book Series), E. Arun K. Shukla (Elsevier), Vol.142, pp. 173-186. [PMID: 28964335] 2. &lquo;Conformational an Thermoynamic Lanscape of GPCR Activation From Theory an Computation&rquo;; Dong SS, Goar WA 3r, Abrol R (2016), Biophysical Journal, 110(12):2618-29. [PMID: 27332120] 3. &lquo;Structure-Base Sequence Alignment of the Transmembrane Domains of all Human GPCRs: Phylogenetic, Structural an Functional Implications&rquo;; Cvicek V, Goar WA 3r, Abrol R (2016), PLoS Computational Biology, 12(3):e1004805. [PMID: 27028541] 4. &lquo;Computational Preiction an Biochemical Analyses of New Inverse Agonists for the CB1 Receptor&rquo;; Scott CE, Ahn KH, Graf ST, Goar WA 3r, Kenall DA, Abrol R (2016). J Chem Inf Moel, 56(1):201-212. [PMID: 26633590] 5. &lquo;FOXC1 Activates Smoothene-Inepenent Hegehog Signaling in Basal-like Breast Cancer&rquo;; Han B, Qu Y, Jin Y, Yu Y, Deng N, Wawrowsky K, Zhang X, Li N, Bose S, Wang Q, Sakkiah S, Abrol R, Jensen TW, Benjamin B, Tanaka H, Johnson J, Gao B, Hao J, Liu Z, Buttyan R, Ray PS, Hung MC, Giuliano AE, Cui X (2015). Cell Reports, 13(5):1046-58. [PMID: 26565916] 6. &lquo;The interaction of N-glycans in Fcγ receptor I α-chain with Escherichia coli K1 outer membrane protein A for entry into macrophages: experimental an computational analysis&rquo;; Krishnan S, Liu F, Abrol R, Hoges J, Goar WA 3r, Prasaarao NV (2014). J Biol Chem, 289(45):30937-49. [PMID: 25231998] 7. &lquo;Ligan- an mutation-inuce conformational selection in the CCR5 chemokine G protein-couple receptor&rquo;; Abrol R, Trzaskowski B, Goar WA 3r, Nesterov A, Olave I, Irons C (2014). Proc Natl Aca Sci, 111(36):13040-5. [PMID: 25157173] 8. &lquo;The SuperBiHelix Metho for Preicting the Pleiotropic Ensemble of G-Protein Couple Receptor Conformations&rquo;; Bray JK, Abrol R, Goar WA 3r, Trzaskowski B, Scott CE (2013). Proc Nat Aca Sci, 111(1):E72-8. [PMID: 24344284] 9. &lquo;The glove-like structure of the conserve membrane protein TatC provies insight into signal sequence recognition in twin-arginine translocation&rquo;; Ramasamy S, Abrol R, Suloway CJ, Clemons WM Jr. (2013). Structure 21(5):777-88. [PMID: 23583035] 10. &lquo;Computationally-preicte CB1 cannabinoi receptor mutants show istinct patterns of salt-briges that correlate with their level of constitutive activity reflecte in G protein coupling levels, thermal stability, an ligan bining&rquo;; Ahn KH, Scott CE, Abrol R, Goar WA 3r, Kenall DA (2013). Proteins, 81(8):1304-17. [PMID: 23408552] 11. &lquo;Conformational Ensemble View of G Protein-Couple Receptors an the Effect of Mutations an Ligan Bining&rquo;; Abrol R, Kim SK, Bray JK, Trzaskowski B, Goar WA 3r (2013). G Protein-Couple Receptors (Methos in Enzymology), E. Conn PM (Elsevier, Oxfor), Vol.520, pp. 31-48. PMID: 23332694 12. &lquo;Molecular basis for ramatic changes in cannabinoi CB1 G protein-couple receptor activation upon single an ouble point mutations&rquo;; Scott CE, Abrol R, Ahn KH, Kenall DA, Goar WA 3r (2013). Protein Science, 22(1):101-13. [PMID: 23184890] 13. &lquo;The Preicte Structure of Agonist-Boun Glucagon-Like Peptie 1 Receptor, a Class B G Protein-Couple Receptor&rquo;; Kirkpatrick A, Heo J, Abrol R, Goar WA 3r (2012). Proc Nat Aca Sci, 109(49):19988-93. [PMID: 23169631] 14. &lquo;Structure Preiction of G Protein-Couple Receptors an Their Ensemble of Functionally Important Conformations&rquo;; Abrol R, Griffith AR, Bray JK, Goar WA 3r (2012). Membrane Protein Structure: Methos an Protocols (Methos in Molecular Biology), Es. Vaiehi N an Klein-Seetharaman J (Humana, New York), Vol.914, pp. 237-54. PMID: 22976032 15. &lquo;The 3D structure preiction of TAS2R38 bitter receptors boun to agonists phenylthiocarbamie (PTC) an 6-n-Propylthiouracil (PROP)&rquo;; Tan J, Abrol R, Trzaskowski B, Goar WA 3r (2012). J Chem Inf Moel, 52:1875-85. [PMID: 22656649] 16. &lquo;Molecular basis for the interplay of apoptosis an proliferation meiate by Bcl-xL:Bim interactions in pancreatic cancer cells&rquo;; Abrol R, Eerkaoui M, Goar WA 3r, Panol SJ (2012). Biochem Biophys Res Commun, 422(4):596-601. [PMID: 22609401] 17. &lquo;BiHelix: Towars e novo Structure Preiction of an Ensemble of G-Protein Couple Receptor Conformations&rquo;; Abrol R, Bray JK, Goar WA 3r (2012). Prot Struc Func Bioinf, 80(2):505-18. [PMID: 22173949] 18. &lquo;Characterizing an Preicting the Functional an Conformational Diversity of Seven-Transmembrane Proteins&rquo;; Abrol R, Kim SK, Bray JK, Griffith AR, Goar WA 3r (2011). Methos, 55(4):405-14. PMID: 22197575 19. &lquo;Experimental valiation of the preicte bining site of Escherichia coli K1 outer membrane protein A to human brain microvascular enothelial cells: ientification of critical mutations that prevent E. coli meningitis&rquo;; Pascal TA, Abrol R, Mittal R, Wang Y, Prasaarao NV, Goar WA 3r (2010). J Biol Chem, 285(48):37753-61. [PMID: 20851887] 20. &lquo;Biological Chiral Recognition: A Substrate’s Perspective&rquo;; Sunaresan V, Abrol R (2005). Chirality, 17(Suppl):S30-9. [PMID: 15736174] 21. &lquo;Towars a general moel for protein-substrate stereoselectivity&rquo;; Sunaresan V, Abrol R (2002). Protein Sci, 11(6): 1330-9. [PMID: 12021432]