Marta Filizola, PhD
- PROFESSOR | Pharmacological Sciences
- PROFESSOR | Neuroscience
- DEAN FOR THE GRADUATE SCHOOL OF BIOMEDICAL SCIENCES
Research Topics: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
Dr. Filizola is the Sharon & Frederick A. Klingenstein-Nathan G. Kase, MD Professor and the Dean of the Graduate School of Biomedical Sciences. She is a dedicated leader in computational biophysics of membrane proteins with over 20 years of experience in the application of methods of computational and theoretical chemistry to biochemical and biomedical problems, as well as to rational drug design. A native of Italy, Dr. Filizola received her Bachelor’s and Master’s degrees in Chemistry from the University Federico II in Naples. She earned her PhD in Computational Chemistry from the Second University of Naples, though conducting most of her doctoral studies at the Department of Chemical Engineering of the Polytechnic University of Catalonia in Barcelona, Spain. She went on to earn a postdoctorate in Computational Biophysics from the Molecular Research Institute in California. Dr. Filizola’s research program is mainly focused on G Protein-Coupled Receptors (GPCRs), which are the targets for about half of all currently used drugs. Special effort in her lab has been devoted to the subfamily of opioid receptors to discover/design novel painkillers with reduced abuse liability and other adverse effects. A second important line of investigation in the Filizola lab is on beta3 integrins towards the discovery of novel therapeutics to treat renal, hematologic, neoplastic, bone, and/or fibrotic diseases. For more information, please visit the Filizola Laboratory website.
Dr. Filizola’s computational methodologies are closely intertwined with collaborative experimental investigations to provide new and biologically relevant insights into signal transduction processes triggered by molecular recognition, giving rise to new hypotheses to guide further experimental inquiry. Dr. Filizola is the author of several patents and over 100 publications in the field of computational biophysics. She is currently a tenured Full Professor in the Department of Pharmacological Sciences, and the Department of Neuroscience. She was appointed Dean of the Graduate School of Biomedical Sciences at Sinai in 2016.
Multi-Disciplinary Training AreaPharmacology and Therapeutics Discovery [PTD]
BS, University of Naples 'Federico II'
MS, University of Naples 'Federico II'
PhD, II University of Naples
Postdoc, Molecular Research Institute
Delta Omega Public Health Honorary Induction
ISQBP Loew Lectureship
Independent Scientist Award (KO2)
The Doctor Harold and Golden Lamport Award for Excellence in Basic Research
National Research Service Award
Title of European Doctor 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 recent, collaborative patent applications demonstrate.
The Filizola Laboratory uses computational structural biology tools, ranging from molecular modeling, bioinformatics, chemoinformatics, molecular dynamics simulations, rational drug design, and machine learning 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 several collaborations with world-renowned experimental leaders, as well as 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.
Hughes TE, Lodowski DT, Huynh KW, Yazici A, Del Rosario J, Kapoor A, Basak S, Samanta A, Han X, Chakrapani S, Zhou ZH, Filizola M, Rohacs T, Han S, Moiseenkova-Bell VY. Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM. Nature structural & molecular biology 2018 Jan; 25(1).
Zafar H, Shang Y, Li J, David GA, Fernandez JP, Molina H, Filizola M, Coller BS. αIIbβ3 binding to a fibrinogen fragment lacking the γ-chain dodecapeptide is activation dependent and EDTA inducible. Blood advances 2017 Feb; 1(7).
Marino KA, Filizola M. Investigating Small-Molecule Ligand Binding to G Protein-Coupled Receptors with Biased or Unbiased Molecular Dynamics Simulations. Methods in molecular biology (Clifton, N.J.) 2018; 1705.
Yano H, Provasi D, Cai NS, Filizola M, Ferré S, Javitch JA. Development of novel biosensors to study receptor-mediated activation of the G-protein α subunits G and G. The Journal of biological chemistry 2017 12; 292(49).
Kapoor A, Martinez-Rosell G, Provasi D, de Fabritiis G, Filizola M. Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity. Scientific reports 2017 Sep; 7(1).
Marino KA, Shang Y, Filizola M. Insights into the function of opioid receptors from molecular dynamics simulations of available crystal structures. British journal of pharmacology 2017 Mar;.
Marino KA, Prada-Gracia D, Provasi D, Filizola M. Impact of Lipid Composition and Receptor Conformation on the Spatio-temporal Organization of μ-Opioid Receptors in a Multi-component Plasma Membrane Model. PLoS computational biology 2016 Dec; 12(12).
Crowley RS, Riley AP, Sherwood AM, Groer CE, Shivaperumal N, Biscaia M, Paton K, Schneider S, Provasi D, Kivell BM, Filizola M, Prisinzano TE. Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Identification of a Potent and Centrally Acting μ Opioid Analgesic with Reduced Abuse Liability. Journal of medicinal chemistry 2016 Dec; 59(24).
Schneider S, Provasi D, Filizola M. How Oliceridine (TRV-130) Binds and Stabilizes a μ-Opioid Receptor Conformational State That Selectively Triggers G Protein Signaling Pathways. Biochemistry 2016 Nov; 55(46).
Wardman JH, Gomes I, Bobeck EN, Stockert JA, Kapoor A, Bisignano P, Gupta A, Mezei M, Kumar S, Filizola M, Devi LA. Identification of a small-molecule ligand that activates the neuropeptide receptor GPR171 and increases food intake. Science signaling 2016 05; 9(430).
Kruegel AC, Gassaway MM, Kapoor A, Váradi A, Majumdar S, Filizola M, Javitch JA, Sames D. Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators. Journal of the American Chemical Society 2016 06; 138(21).
Shang Y, Yeatman HR, Provasi D, Alt A, Christopoulos A, Canals M, Filizola M. Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors. ACS chemical biology 2016 05; 11(5).
Filizola M. Preface. G Protein-Coupled Receptors in Drug Discovery. Methods in molecular biology (Clifton, N.J.) 2015; 1335.
Bisignano P, Burford NT, Shang Y, Marlow B, Livingston KE, Fenton AM, Rockwell K, Budenholzer L, Traynor JR, Gerritz SW, Alt A, Filizola M. Ligand-Based Discovery of a New Scaffold for Allosteric Modulation of the μ-Opioid Receptor. Journal of chemical information and modeling 2015 Sep; 55(9).
Schneider S, Provasi D, Filizola M. The Dynamic Process of Drug-GPCR Binding at Either Orthosteric or Allosteric Sites Evaluated by Metadynamics. Methods in molecular biology (Clifton, N.J.) 2015; 1335.
Shang Y, Filizola M. Opioid receptors: Structural and mechanistic insights into pharmacology and signaling. European journal of pharmacology 2015 Sep; 763(Pt B).
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 Oct; 34(10).
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 multimicrosecond, all-atom molecular dynamics simulations. Proteins 2014 Dec; 82(12).
Johnston JM, Filizola M. Differential stability of the crystallographic interfaces of mu- and kappa-opioid receptors. PloS one 2014; 9(2).
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).
Filizola M. Insights from molecular dynamics simulations to exploit new trends for the development of improved opioid drugs. Neuroscience letters 2018 Feb;.