Addiction, Bioinformatics, Biophysics, Computational Biology, Computer Simulation, Drug Design and Discovery, Integrins, Mathematical and Computational Biology, Membrane Proteins/Channels, Opioid/Cannabinoid Receptors, Protein Complexes, Protein Structure/Function, Receptors, Signal Transduction, Structural Biology, Theoretical Biology, Theoretical Biophysics, Transporters
Biophysics and Systems Pharmacology [BSP]
BS, University of Naples 'Federico II'
MS, University of Naples 'Federico II'
PhD, II University of Naples
Postdoc, Molecular Research Institute
Independent Scientist Award (KO2)
The Doctor Harold and Golden Lamport Award for Excellence in Basic Research
Mount Sinai School of Medicine
National Research Service Award T32 DA07135
National Institute on Drug Abuse (NIDA)
Title of European Doctor in Biotechnology
European Association for Higher Education in Biotechnology
Computational Biophysics of Membrane Proteins
The overall goal of current research programs in the Filizola Laboratory is to obtain rigorous mechanistic insight into the structure, dynamics, and function of important classes of membrane proteins that are prominent drug targets of the human ‘druggable’ genome (e.g., G protein-coupled receptors (GPCRs), integrins, etc.) for the purpose of developing improved therapeutics. Understanding the molecular mechanisms underlying the complex biological functions of these proteins has direct translational relevance because it informs the rational discovery of potentially improved therapeutic agents, as a recent, collaborative patent application on novel anti-thrombotic agents (with Dr. Barry Coller at Rockefeller University) demonstrates.
The Filizola Laboratory uses computational structural biology tools, ranging from molecular modeling, bioinformatics, chemoinformatics, simulation, and rational drug design approaches. Their research requires complementary, multi-disciplinary expertise in biological, medical, and quantitative sciences, and as such, it strongly relies on team science as demonstrated by recent collaborations with world-renowned experimental leaders, as well as recent publications in Cell, Nature, Science Translational Medicine, PNAS, Blood, etc. Through application and implementation of cutting-edge developments in theory and simulation, the Filizola Laboratory contributes a level of molecular detail that is impossible or difficult to obtain experimentally. This information lays the foundation for novel experimental studies aimed at furthering current understanding of physiological functions, and at developing new therapeutic strategies.
Shang Y, Filizola M. Opioid receptors: Structural and mechanistic insights into pharmacology and signaling. European journal of pharmacology 2015 May;.
Burford NT, Livingston KE, Canals M, Ryan MR, Budenholzer LM, Han Y, Shang Y, Herbst JJ, O'Connell J, Banks M, Zhang L, Filizola M, Bassoni DL, Wehrman TS, Christopoulos A, Traynor JR, Gerritz SW, Alt A. Discovery, Synthesis, and Molecular Pharmacology of Selective Positive Allosteric Modulators of the δ-Opioid Receptor. Journal of medicinal chemistry 2015 May; 58(10).
Buitrago L, Rendon A, Liang Y, Simeoni I, Negri A, Filizola M, Ouwehand WH, Coller BS. αIIbβ3 variants defined by next-generation sequencing: predicting variants likely to cause Glanzmann thrombasthenia. Proceedings of the National Academy of Sciences of the United States of America 2015 Apr; 112(15).
Provasi D, Boz MB, Johnston JM, Filizola M. Preferred supramolecular organization and dimer interfaces of opioid receptors from simulated self-association. PLoS computational biology 2015 Mar; 11(3).
Li J, Vootukuri S, Shang Y, Negri A, Jiang JK, Nedelman M, Diacovo TG, Filizola M, Thomas CJ, Coller BS. RUC-4: A Novel αIIbβ3 Antagonist for Prehospital Therapy of Myocardial Infarction. Arteriosclerosis, thrombosis, and vascular biology 2014 Aug;.
Shang Y, LeRouzic V, Schneider S, Bisignano P, Pasternak GW, Filizola M. Mechanistic insights into the allosteric modulation of opioid receptors by sodium ions. Biochemistry 2014 Aug; 53(31).
Provasi D, Negri A, Coller BS, Filizola M. Talin-driven inside-out activation mechanism of platelet αIIbβ3 integrin probed by multi-microsecond, all-atom molecular dynamics simulations. Proteins 2014 Feb;.
Johnston JM, Filizola M. Differential stability of the crystallographic interfaces of mu- and kappa-opioid receptors. PloS one 2014; 9(2).
Jiang JK, McCoy JG, Shen M, Leclair CA, Huang W, Negri A, Li J, Blue R, Harrington AW, Naini S, David G, Choi WS, Volpi E, Fernandez J, Babayeva M, Nedelman MA, Filizola M, Coller BS, Thomas CJ. A novel class of ion displacement ligands as antagonists of the αIIbβ3 receptor that limit conformational reorganization of the receptor. Bioorganic & medicinal chemistry letters 2014 Feb; 24(4).
Ferré S, Casadó V, Devi LA, Filizola M, Jockers R, Lohse MJ, Milligan G, Pin JP, Guitart X. G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives. Pharmacological reviews 2014; 66(2).
Johnston JM, Filizola M. Beyond standard molecular dynamics: investigating the molecular mechanisms of g protein-coupled receptors with enhanced molecular dynamics methods. Advances in experimental medicine and biology 2014; 796.
Mondal S, Johnston JM, Wang H, Khelashvili G, Filizola M, Weinstein H. Membrane driven spatial organization of GPCRs. Scientific reports 2013; 3.
Gomes I, Fujita W, Gupta A, Saldanha SA, Saldanha AS, Negri A, Pinello CE, Roberts E, Filizola M, Hodder P, Devi LA. Identification of a μ-δ opioid receptor heteromer-biased agonist with antinociceptive activity. Proceedings of the National Academy of Sciences of the United States of America 2013 Jul; 110(29).
Scarabelli G, Provasi D, Negri A, Filizola M. Bioactive conformations of two seminal delta opioid receptor penta-peptides inferred from free-energy profiles. Biopolymers 2014 Jan; 101(1).
Negri A, Rives ML, Caspers MJ, Prisinzano TE, Javitch JA, Filizola M. Discovery of a Novel Selective Kappa-Opioid Receptor Agonist Using Crystal Structure-Based Virtual Screening. Journal of chemical information and modeling 2013 Mar;.
Coudray N, Valvo S, Hu M, Lasala R, Kim C, Vink M, Zhou M, Provasi D, Filizola M, Tao J, Fang J, Penczek PA, Ubarretxena-Belandia I, Stokes DL. Inward-facing conformation of the zinc transporter YiiP revealed by cryoelectron microscopy. Proceedings of the National Academy of Sciences of the United States of America 2013 Feb; 110(6).
Filizola M, Devi LA. Grand opening of structure-guided design for novel opioids. Trends in pharmacological sciences 2013 Jan; 34(1).
Negri A, Li J, Naini S, Coller BS, Filizola M. Structure-based virtual screening of small-molecule antagonists of platelet integrin αIIbβ3 that do not prime the receptor to bind ligand. Journal of computer-aided molecular design 2012 Sep; 26(9).
Johnston JM, Wang H, Provasi D, Filizola M. Assessing the relative stability of dimer interfaces in g protein-coupled receptors. PLoS computational biology 2012; 8(8).
Filizola M, Devi LA. Structural biology: How opioid drugs bind to receptors. Nature 2012 May; 485(7398).
Zhu J, Choi WS, McCoy JG, Negri A, Zhu J, Naini S, Li J, Shen M, Huang W, Bougie D, Rasmussen M, Aster R, Thomas CJ, Filizola M, Springer TA, Coller BS. Structure-Guided Design of a High-Affinity Platelet Integrin αIIbβ3 Receptor Antagonist That Disrupts Mg2+ Binding to the MIDAS. Science Translational Medicine 2012 Mar; 4(125).
Fribourg M, Moreno JL, Holloway T, Provasi D, Baki L, Mahajan R, Park G, Adney SK, Hatcher C, Eltit JM, Ruta JD, Albizu L, Li Z, Umali A, Shim J, Fabiato A, MacKerell AD, Brezina V, Sealfon SC, Filizola M, González-Maeso J, Logothetis DE. Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell 2011 Nov; 147(5).
Provasi D, Artacho MC, Negri A, Mobarec JC, Filizola M. Ligand-induced modulation of the free-energy landscape of G protein-coupled receptors explored by adaptive biasing techniques. PLoS computational biology 2011 Oct; 7(10).
Johnston JM, Filizola M. Showcasing modern molecular dynamics simulations of membrane proteins through G protein-coupled receptors. Current opinion in structural biology 2011 Aug; 21(4).
Johnston JM, Aburi M, Provasi D, Bortolato A, Urizar E, Lambert NA, Javitch JA, Filizola M. Making structural sense of dimerization interfaces of delta opioid receptor homodimers. Biochemistry 2011 Mar; 50(10).
Wang H, Barreyro L, Provasi D, Djemil I, Torres-Arancivia C, Filizola M, Ubarretxena-Belandia I. Molecular determinants and thermodynamics of the amyloid precursor protein transmembrane domain implicated in Alzheimer's disease. Journal of molecular biology 2011 May; 408(5).
Golebiewska U, Johnston JM, Devi L, Filizola M, Scarlata S. Differential response to morphine of the oligomeric state of μ-opioid in the presence of δ-opioid receptors. Biochemistry 2011 Apr; 50(14).
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Dr. Filizola has not yet completed reporting of Industry relationships.
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