Education
M.S., University of Naples 'Federico II'
ChemistryB.S., University of Naples 'Federico II'
ChemistryPh.D., II University of Naples
Computational ChemistryPostdoc, 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. As such, she has recently been elected a worthy recipient of the 2008 Harold and Golden Lamport Award for Excellence in Basic Research, a prestigious award given to tenure-track Assistant Professors at Mount Sinai who demonstrate exceptional potential for making significant contributions in the early stage of their academic career.
Awards
2009 - present
Independent Scientist Award (KO2)
NIH-NIDA2008 -
The Doctor Harold and Golden Lamport Award for Excellence in Basic Research
Mount Sinai School of Medicine2001 -
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 our research is to achieve a detailed mechanistic understanding of signal transduction processes triggered by molecular recognition by means of computational methodologies that range from bioinformatics to modeling and simulation. The strength of our research relies on the integration of these computational methodologies with collaborative experimental approaches to provide valuable mechanistic interpretations at the molecular level of the ligand-induced transmission of the signal to the inner side of the cell membrane. While our research is driven by the exploration and improvement of computational methods to characterize generalizable mechanisms of molecular recognition and signal transduction, we are excited by the contributions that our computational and modeling efforts make to the experimental field through the generation of new testable hypotheses. Current major research activities in the lab include:
1) Structural Aspects of Oligomerization in the Function of G Protein-Coupled Receptors (GPCRs);
2) Exploration of Membrane Protein Processes Using Enhanced Sampling Methods;
3) Elucidation of integrin allostery and bidirectional signaling.
For more information, please visit the Filizola Laboratory website.
Publications
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).
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).
Zhu J, Zhu J, Negri A, Provasi D, Filizola M, Coller BS, Springer TA. Closed headpiece of integrin αIIbβ3 and its complex with an αIIbβ3-specific antagonist that does not induce opening. Blood 2010 Dec; 116(23).
Provasi D, Filizola M. Putative active states of a prototypic g-protein-coupled receptor from biased molecular dynamics. Biophysical journal 2010 May; 98(10).
Blue R, Li J, Steinberger J, Murcia M, Filizola M, Coller BS. Effects of limiting extension at the alphaIIb genu on ligand binding to integrin alphaIIbbeta3. The Journal of biological chemistry 2010 Jun; 285(23).
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).
Provasi D, Bortolato A, Filizola M. Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics. Biochemistry 2009 Oct; 48(42).
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).
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 Mount Sinai School of Medicine 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 2011 and/or 2012: 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://www.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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