Aviv Paz Ph.D.
Aviv Paz
Ph.D.
Research Assistant Professor
Department of Structural Biology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Membrane Proteins; Protein Function and Structure; Structural Biology; X-ray Crystallography
Professional Summary:
My laboratory studies the structure, function, and the relationship between structure and function in membrane transport proteins. Transporters undergo isomerization, transitioning between distinct conformations to ferry cargo across lipidic membranes. We are especially interested in deciphering the forces that energize transport, the determinants of ligand selection (given the spectrum from high specificity to multispecificity among transporters), and deciphering the structural dynamics governing conformational changes in transporters.
To probe these captivating facets of transport, we harness a diverse array of structural biology techniques, including X-ray crystallography, cryogenic electron microscopy (cryo-EM), and X-ray scattering. Complementing these methods, we employ a suite of biochemical and biophysical assays to characterize purified proteins, whether solubilized in detergents or reconstituted in lipids. Additionally, we conduct various cellular assays and collaborate closely with computational scientists proficient in molecular dynamics simulations and other computational methodologies to enrich our experimental insights.
Our main focus is the Organic Anion Transporting Polypeptide superfamily, which plays pivotal roles in numerous physiological processes, encompassing drug disposition, potential life-threatening drug-drug interactions, and the management and progression of specific cancers.
Furthermore, the field of cryo-EM has witnessed substantial advancements in recent years, yet challenges persist, particularly concerning sample stability and dispersion on cryo-EM grids. To address these hurdles, we are developing novel tools for sample handling and freezing. Our aim is to minimize the occurrence of denatured particles on grids and mitigate issues such as preferred particle orientations, thereby enhancing the efficacy and reliability of cryo-EM analyses.
Education and Training:
- PhD, Structural Biology, Weizmann Institute of Science (2009)
- MS, Biophysics, Bar-Ilan University, Cum Laude (2003)
- BS, Medical Sciences, Tel-Aviv University (1999)
Employment:
- Research Assistant Professor, Structural Biology, UB, Jacobs School of Medicine and Biomedical Sciences (2024-present)
- Assistant Investigator, Hauptman-Woodward Medical Research Institute (2022-present)
- Adjunct Associate Professor of Oncology, Roswell Park Comprehensive Cancer Center (2018-present)
- Associate Research Scientist, Hauptman-Woodward Medical Research Institute (2018–2022)
- Project Scientist, Physiology, David Geffen School of Medicine, University of California Los-Angeles (2014–2018)
Awards and Honors:
- Seymore H. Knox Foundation Research Award (2021)
- The Joseph and Anna Gartner Foundation Research Award (2021)
- The Sonnenschein Fund Postdoctoral Award (2012)
Research Expertise:
- “Classical” structural biology: We routinely employ X-ray crystallography (using the excellent facilities at the HWI), cryogenic electron microscopy (in HWI and with other collaborators), protein modeling, and ligand docking to solve structures of membrane and soluble protein targets.
- Biochemical/biophysical characterization: We perform numerous assays locally and at synchrotron facilities to tease out various biochemical and biophysical aspects important for the functions of our targets.
- Cellular assays: We employ various functional assays such as uptakes of fluorescent ligands, cell-surface abundance, etc., to characterize the proteins in cells overexpressing our targets. Findings are compared to results of detergent solubilized proteins and reconstituted systems (that only contain our protein of interest) to gain insight into the influence of other cellular components on our targets.
- Heterologous protein overexpression: My lab uses bacterial, yeast, and cell lines for the overexpression of our targets.
- Membrane proteins: Due to the hydrophobic nature of membrane proteins special handling using detergents is required for the solubilization, purification, and characterization of these proteins. Furthermore, to biochemically/biophysically study these purified proteins in lipidic environments (which are much closer to the native environment than detergents) reconstitution of detergent-solubilized proteins in lipidic environments such as proteoliposomes, nanodiscs, bicelles, etc., are routinely performed in the lab.
- Method development: My research style is very receptive for improving existing methods and developing new ideas related to structural biology and protein purification.
- Protein purification: We utilize multiple affinity systems, ion-exchange, and size-exclusion chromatography utilizing gravity and FPLC systems.
Grants and Sponsored Research:
- April 2023–March 2027
Structure meets function for OATP1B1, a transporter involved in the uptake of endogenous and xenobiotic materials and drugs
National Institutes of Health
Role: Principal Investigator - April 2022–May 2025
Structure/Function Relationship of Organic Anion Transporting Polypeptide 1B3
G. Harold and Leila Y. Mathers Charitable Foundation
Role: Principal Investigator - January 2022–January 2023
Chemically engineered bilayers for cryoEM imaging of membrane proteins in continuous membranes
National Institutes of Health
Role: Principal Investigator - December 2020–December 2021
Understanding The Roles of Transport Proteins Involved in Cancer Progression and Treatment
Seymour H. Knox Foundation
Role: Principal Investigator
Journal Articles:
- Khan F, Elgeti M, Grandfield S, Paz A, Naughton FB, Marcoline FV, Althoff T, Ermolova N, Wright EM, Hubbell WL, Grabe M, Abramson J. (2023) Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT. Nature communications (Nov), 14(1): 7511. doi:10.1038/s41467-023-43119-z
- Premageetha GTR, Dhanabalan K, Bose S, Manjunath L, Joseph D, Paz A, Grandfield S, Nayak V, Bredeston LM, Abramson J, Ramaswamy S. (2023) Biochemical characterization of a GDP-mannose transporter from Chaetomium thermophilum. PloS one (Jan), 18(4): e0280975. doi:10.1371/journal.pone.0280975
- Hayden ER, Chen M, Pasquariello KZ, Gibson AA, Petti JJ, Shen S, Qu J, Ong SS, Chen T, Jin Y, Uddin ME, Huang KM, Paz A, Sparreboom A, Hu S, Sprowl JA. (2021) Regulation of OATP1B1 Function by Tyrosine Kinase-mediated Phosphorylation. Clinical cancer research : an official journal of the American Association for Cancer Research (Aug), 27(15): 4301-4310. doi:10.1158/1078-0432.CCR-21-0023
- Wahlgren WY, Dunevall E, North RA, Paz A, Scalise M, Bisignano P, Bengtsson-Palme J, Goyal P, Claesson E, Caing-Carlsson R, Andersson R, Beis K, Nilsson UJ, Farewell A, Pochini L, Indiveri C, Grabe M, Dobson RCJ, Abramson J, Ramaswamy S, Friemann R. (2018) Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site. Nature communications (May), 9(1): 1753. doi:10.1038/s41467-018-04045-7
- Paz A, Claxton DP, Kumar JP, Kazmier K, Bisignano P, Sharma S, Nolte SA, Liwag TM, Nayak V, Wright EM, Grabe M, Mchaourab HS, Abramson J. (2018) Conformational transitions of the sodium-dependent sugar transporter, vSGLT. Proceedings of the National Academy of Sciences of the United States of America (Mar), 115(12): E2742-E2751. doi:10.1073/pnas.1718451115
- Gorraitz E, Hirayama BA, Paz A, Wright EM, Loo DDF. (2017) Active site voltage clamp fluorometry of the sodium glucose cotransporter hSGLT1. Proceedings of the National Academy of Sciences of the United States of America (Nov), 114(46): E9980-E9988. doi:10.1073/pnas.1713899114
- Srikanth S, Kim KD, Gao Y, Woo JS, Ghosh S, Calmettes G, Paz A, Abramson J, Jiang M, Gwack Y. (2016) A large Rab GTPase encoded by CRACR2A is a component of subsynaptic vesicles that transmit T cell activation signals. Science signaling (Mar), 9(420): ra31. doi:10.1126/scisignal.aac9171
- Li Z, Lee AS, Bracher S, Jung H, Paz A, Kumar JP, Abramson J, Quick M, Shi L. (2015) Identification of a second substrate-binding site in solute-sodium symporters. The Journal of biological chemistry (Jan), 290(1): 127-41. doi:10.1074/jbc.M114.584383
- Choudhary OP, Paz A, Adelman JL, Colletier JP, Abramson J, Grabe M. (2014) Structure-guided simulations illuminate the mechanism of ATP transport through VDAC1. Nature structural & molecular biology (Jul), 21(7): 626-32. doi:10.1038/nsmb.2841
- Schredelseker J, Paz A, López CJ, Altenbach C, Leung CS, Drexler MK, Chen JN, Hubbell WL, Abramson J. (2014) High resolution structure and double electron-electron resonance of the zebrafish voltage-dependent anion channel 2 reveal an oligomeric population. The Journal of biological chemistry (May), 289(18): 12566-77. doi:10.1074/jbc.M113.497438
- Silman I, Roth E, Paz A, Triquigneaux MM, Ehrenshaft M, Xu Y, Shnyrov VL, Sussman JL, Deterding LJ, Ashani Y, Mason RP, Weiner L. (2013) The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy. Chemico-biological interactions (Mar), 203(1): 63-6.
- Vartanian AS, Paz A, Fortgang EA, Abramson J, Dahlquist FW. (2012) Structure of flagellar motor proteins in complex allows for insights into motor structure and switching. The Journal of biological chemistry (Oct), 287(43): 35779-83. doi:10.1074/jbc.C112.378380
- Paz A, Roth E, Ashani Y, Xu Y, Shnyrov VL, Sussman JL, Silman I, Weiner L. (2012) Structural and functional characterization of the interaction of the photosensitizing probe methylene blue with Torpedo californica acetylcholinesterase. Protein science : a publication of the Protein Society (Aug), 21(8): 1138-52. doi:10.1002/pro.2101
- Wood K, Paz A, Dijkstra K, Scheek RM, Otten R, Silman I, Sussman JL, Mulder FA. (2012) Backbone and side chain NMR assignments for the intrinsically disordered cytoplasmic domain of human neuroligin-3. Biomolecular NMR assignments (Apr), 6(1): 15-8. doi:10.1007/s12104-011-9315-4
- Abramson J, Paz A, Philipson KD. (2012) Structural biology. It's all in the symmetry. Science (New York, N.Y.) (Feb), 335(6069): 669-70. doi:10.1126/science.1218696
- Xu Y, Li MJ, Greenblatt H, Chen W, Paz A, Dym O, Peleg Y, Chen T, Shen X, He J, Jiang H, Silman I, Sussman JL. (2012) Flexibility of the flap in the active site of BACE1 as revealed by crystal structures and molecular dynamics simulations. Acta crystallographica. Section D, Biological crystallography (Jan), 68(Pt 1): 13-25.
- Zeev-Ben-Mordehai T, Mylonas E, Paz A, Peleg Y, Toker L, Silman I, Svergun DI, Sussman JL. (2009) The quaternary structure of amalgam, a Drosophila neuronal adhesion protein, explains its dual adhesion properties. Biophysical journal (Oct), 97(8): 2316-26. doi:10.1016/j.bpj.2009.07.045
- Paz A, Xie Q, Greenblatt HM, Fu W, Tang Y, Silman I, Qiu Z, Sussman JL. (2009) The crystal structure of a complex of acetylcholinesterase with a bis-(-)-nor-meptazinol derivative reveals disruption of the catalytic triad. Journal of medicinal chemistry (Apr), 52(8): 2543-9.
- Zeev-Ben-Mordehai T, Paz A, Peleg Y, Toker L, Wolf SG, Rydberg EH, Sussman JL, Silman I. (2009) Amalgam, an axon guidance Drosophila adhesion protein belonging to the immunoglobulin superfamily: over-expression, purification and biophysical characterization. Protein expression and purification (Feb), 63(2): 147-57.
- Ben-David M, Noivirt-Brik O, Paz A, Prilusky J, Sussman JL, Levy Y. (2009) Assessment of CASP8 structure predictions for template free targets. Proteins (Jan), 77 Suppl 9: 50-65.
- Paz A, Zeev-Ben-Mordehai T, Lundqvist M, Sherman E, Mylonas E, Weiner L, Haran G, Svergun DI, Mulder FA, Sussman JL, Silman I. (2008) Biophysical characterization of the unstructured cytoplasmic domain of the human neuronal adhesion protein neuroligin 3. Biophysical journal (Aug), 95(4): 1928-44. doi:10.1529/biophysj.107.126995
- Tsvetkov P, Asher G, Paz A, Reuven N, Sussman JL, Silman I, Shaul Y. (2008) Operational definition of intrinsically unstructured protein sequences based on susceptibility to the 20S proteasome. Proteins (Mar), 70(4): 1357-66.
Professional Memberships:
- Protein Society (2022–present)
- American Crystallographic Association (2019–present)
- American Association for the Advancement of Science (2012–2014)
Presentations:
- "Exploratory Studies of Two Transporter Families; Towards Structural Determination" Protein Science Group Seminar Series (2020)
- "Structural Studies of The Equilibrative Nucleoside Transporter Family" IMCA-CAT board meeting, Advanced Photon Sources (2020)
- "Functional basis of conformational transitions in the sodium dependent sugar transporter vSGLT" Biochemistry Department Seminar University at Buffalo (2019)
- "Deciphering Ligand Induced Conformational Changes in Two Families of Sodium Dependent Sugar Transporters" ILANIT/FISEB conference (2017)
- "Double Electron-Electron Resonance Studies of vSGLT Under Different Ligand Conditions" Transporter Interest Group meeting, University of California San Francisco (2015)
- "Structural Exploration of the Voltage Dependent Anion Channel" Physiology Department Seminar, University of California Los-Angeles (2014)
- "Structural Studies on Cholinesterase-like Adhesion Molecules" Neurobiology Department Symposium, Weizmann Institute of Science (2007)
- "Are Intrinsically Unfolded Proteins Really Unstructured?" Structural Biology Symposium, Weizmann Institute of Science (2005)
Service Activities:
- Nature Communications; Reviewer (2024–present)
- American Crystallographic Association's 74th Annual Meeting.; Pauling Prize Judge (2024)
- Applied Crystallization Workshop, National Crystallization Center; Instructor (2024)
- Department of Structural Biology and the Hauptman-Woodward Institute Seminar Series; Co-organizer (2024–present)
- Terra Western New York STEM and Education Fair; Judge (2024)
- Frontiers in Molecular Biosciences; Review Editor (2023–present)
- HWI Scientific Governance Council; Member (2023–present)
- HWI Faculty Search Committee; Chair (2023–2024)
- G. Harold and Leila Y. Mathers Charitable Foundation; Review Board Member (2023–present)
- Eukaryotic Cell Anatomy and Transport, Unit 1: Genomes, Graduate Course, Roswell Park Comprehensive Cancer Center; Lecturer (2022–present)
- HWI Safety Committee; Member (2022–present)
- Journal of Molecular Biology; Reviewer (2021–present)
- Proteins Structure Function & Bioinformatics; Reviewer (2021–present)
- HWI Scientific Governance Council; Secretary (2020–2023)
- HWI/IMCA-CAT Seminar Series Committee; Chair (2020–present)
- HWI Structural Biology Workshop; Lecturer (2018)
- Protein Purification and Characterization Course, Weizmann Institute of Science; Lecturer and Laboratory Instructor (2018–2020)
- Structure; Reviewer (2017–present)
- Foundations of Medicine Block I, David Geffen School of Medicine, University of California Los-Angeles; Problem Based Learning Instructor (2016–2017)
- EMBO Reports; Reviewer (2016–present)
- Proceedings of the National Academy of Sciences; Reviewer (2016–present)
- International Union of Crystallography Journal; Reviewer (2016–present)
- Laboratory Instructor; Foundations of Medicine Block II, David Geffen School of Medicine, University of California Los-Angeles (2014–2015)
- Membrane Protein Crystallization Workshop, InStem Bangalore India; Lecturer, Laboratory Coordinator and Instructor (2013)
- New Strategies for Cloning and Expression of Protein Complexes in E. coli and Insect Cells, Spine2 Complexes Workshop; Laboratory Instructor (2009)
- 3D visualization theater and young@science, Weizmann Institute of Science; Lecturer (2005–2009)