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Marta Filizola

  • ASSOCIATE PROFESSOR Structural and Chemical Biology
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Education

  • M.S., University of Naples 'Federico II'
    Chemistry

  • B.S., University of Naples 'Federico II'
    Chemistry

  • Ph.D., II University of Naples
    Computational Chemistry

  • Postdoc, Molecular Research Institute
    Computational Biophysics

Biography

    Dr. Filizola is a dedicated leader in computational biophysics of membrane proteins, with a special focus on the family of cell surface proteins called G protein-coupled receptors (GPCRs), which are the targets for about half of all currently used drugs. A second important line of investigation is on platelet integrin aIIbb3. Her computational methodologies are closely intertwined with collaborative experimental investigations to provide new and biologically relevant insights about the ligand-induced transmission of the signal from the exterior to the interior of the cell membrane, giving rise to new hypotheses to guide further experimental inquiry. Since the start of her academic appointment in July 2007, Dr. Filizola has been actively engaged in and is continuously making important contributions to academic research and educational activities at Mount Sinai as well as in the scientific community in general.

    For more information, please visit the Filizola Laboratory website.


Awards

  • 2009 - present
    Independent Scientist Award (KO2)
    NIH-NIDA

  • 2008 -
    The Doctor Harold and Golden Lamport Award for Excellence in Basic Research
    Mount Sinai School of Medicine

  • 2001 -
    National Research Service Award T32 DA07135
    National Institute on Drug Abuse (NIDA)

  • 1999 -
    Title of European Doctor in Biotechnology
    European Association for Higher Education in Biotechnology

Research

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 on novel anti-thrombotic agents (with Dr. Barry Coller at Rockefeller University) or novel opioid ligands (with Jonathan Javitch at Columbia University) have demonstrated. 

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.

Publications

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).

Provasi D, Johnston JM, Filizola M. Lessons from free energy simulations of delta-opioid receptor homodimers involving the fourth transmembrane helix. Biochemistry 2010 Aug; 49(31).

Provasi D, Bortolato A, Filizola M. Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics. Biochemistry 2009 Oct; 48(42).

Filizola M. Increasingly accurate dynamic molecular models of G-protein coupled receptor oligomers: Panacea or Pandora's box for novel drug discovery?. Life sciences 2010 Apr; 86(15-16).

Provasi D, Filizola M. Putative active states of a prototypic g-protein-coupled receptor from biased molecular dynamics. Biophysical journal 2010 May; 98(10).

González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 2008 Mar; 452(7183).

Khelashvili G, Dorff K, Shan J, Camacho-Artacho M, Skrabanek L, Vroling B, Bouvier M, Devi LA, George SR, Javitch JA, Lohse MJ, Milligan G, Neubig RR, Palczewski K, Parmentier M, Pin JP, Vriend G, Campagne F, Filizola M. GPCR-OKB: the G Protein Coupled Receptor Oligomer Knowledge Base. Bioinformatics (Oxford, England) 2010 Jul; 26(14).

Mobarec JC, Sanchez R, Filizola M. Modern homology modeling of G-protein coupled receptors: which structural template to use?. Journal of medicinal chemistry 2009 Aug; 52(16).

Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M, Javitch JA. Dopamine D2 receptors form higher order oligomers at physiological expression levels. The EMBO journal 2008 Sep; 27(17).

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Filizola did not report having any of the following types of financial relationships with industry during 2013 and/or 2014: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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