Marta Filizola

Marta Filizola
Born	Nola (Naples), (Italy)
Residence	New York, NY, USA
Nationality	Italian, American
Education	Ph.D., II University of Naples, 1999.
Alma mater	University of Naples "Federico II", II University of Naples
Occupation	Dean of The Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai Professor, Department of Pharmacological Sciences, Professor, Department of Neuroscience
Employer	Icahn School of Medicine at Mount Sinai
Known for	Chemistry, Computational Biology, Biophysics
Website	http://www.mountsinai.org/profiles/marta-filizola

Marta Filizola is the Dean of The Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai in New York City.^[1] She is also a Professor of Pharmacological Sciences and Professor of Neuroscience. Filizola is a computational biophysicist who studies membrane proteins^[2] and with extensive experience in the application of methods of computational chemistry and theoretical chemistry to biochemical and biomedical problems, as well as to drug discovery.^[3][4] She is best known for her work aimed at providing mechanistic insight into the structure, dynamics, and function of G protein-coupled receptors^[5][6] using methods such as molecular modeling, bioinformatics, cheminformatics, enhanced molecular dynamics simulations, and rational drug design approaches.

The Filizola laboratory's research has steadily been funded by the National Institutes of Health (NIH) since 2005. As of 2016, Filizola is active in five research projects funded by the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the National Heart, Lung, and Blood Institute (NHLBI).^[7]

Education

A native of Italy, Filizola received her Bachelor’s and master's degrees in Chemistry from the University Federico II in Naples^[8] (class of 1993), and earned her PhD in Computational Chemistry from the Second University of Naples in 1999, though conducting most of her doctoral studies at the Department of Chemical Engineering of the Polytechnic University of Catalonia^[9] in Barcelona, Spain. She went on to pursue a postdoctorate in Computational Biophysics from the Molecular Research Institute^[10] in California, moving to New York City in 2001.

Career

Dr. Filizola joined the Department of Physiology & Biophysics at Mount Sinai School of Medicine (MSSM) as an Instructor in 2002. She continued in this role at Weill Medical College (WMC) of Cornell University,^[11] also in New York City, until she was promoted Assistant Professor in 2005. She returned to Mount Sinai as an Assistant Professor in the Department of Structural and Chemical Biology where she was later promoted Associate Professor (with Tenure since January 2013), and then Full Professor in 2014.^[12] Following three years as Co-Director of the Structural/Chemical Biology and Molecular Design (SMD) Graduate Program, and one year as Co-Director of the Biophysics and Systems Pharmacology (BSP) Graduate Program,^[13] she was appointed Dean of the Graduate School of Biomedical Sciences^[14] at Mount Sinai in May 2016. Dr. Filizola has also served as grant reviewer for NIH and other agencies for over 10 years. Currently, she is a regular study section member of the Biophysics of Neural Systems (BPNS) study section of NIH.^[15]

Awards and honors

Dr. Filizola’s awards and honors include the title of European Doctor in Biotechnology^[16] from the European Association for Higher Education in Biotechnology in Genova, Italy (1999), a National Research Service Award from NIDA (2002), The Doctor Harold and Golden Lamport Award for Excellence in Basic Research from Mount Sinai School of Medicine (2008), and an Independent Scientist Award from NIDA (2009–present).^[17] She is also a Member of the Faculty of 1000 for Pharmacology and Drug Discovery since 2013.^[18]

Research

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.

To obtain rigorous mechanistic insight into the structure, dynamics, and function of GPCRs and beta3 integrins, the Filizola lab uses several computational structural biology tools, ranging from molecular modeling, bioinformatics, cheminformatics, molecular dynamics simulations, a variety of enhanced sampling algorithms, and rational drug design approaches.^[19] Much of the work is done in close collaboration with major experimental labs with whom we have established longstanding synergistic ties.

Dr. Filizola is the author of over 90 original papers and chapters in the areas of computational chemistry/biophysics and drug discovery,^[20] as well as the editor of 2 books: "G Protein-Coupled Receptors - Modeling and Simulation"^[21] and "G Protein-Coupled Receptors in Drug Discovery".^[22] She is also an inventor, with a number of patents to her credit.^[23]

Publications (partial list)

• Pin JP, Neubig R, Bouvier M, Devi L, Filizola M, Javitch JA, Lohse MJ, Milligan G, Palczewski K, Parmentier M, Spedding M (2007). "International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G protein-coupled receptor heteromultimers". Pharmacological Reviews. 59 (1): 5–13. doi:10.1124/pr.59.1.5. PMID 17329545. 
• 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 (2008). "Identification of a serotonin/glutamate receptor complex implicated in psychosis". Nature. 452 (7183): 93–7. Bibcode:2008Natur.452...93G. doi:10.1038/nature06612. PMC 2743172. PMID 18297054. 
• Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M, Javitch JA (2008). "Dopamine D2 receptors form higher order oligomers at physiological expression levels". The EMBO Journal. 27 (17): 2293–304. doi:10.1038/emboj.2008.153. PMC 2529367. PMID 18668123. 
• Mobarec JC, Sanchez R, Filizola M (2009). "Modern homology modeling of G-protein coupled receptors: which structural template to use?". Journal of Medicinal Chemistry. 52 (16): 5207–16. doi:10.1021/jm9005252. PMC 2891345. PMID 19627087. 
• Provasi D, Bortolato A, Filizola M (2009). "Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics". Biochemistry. 48 (42): 10020–9. doi:10.1021/bi901494n. PMC 2764813. PMID 19785461. 
• 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 (2010). "GPCR-OKB: the G Protein Coupled Receptor Oligomer Knowledge Base". Bioinformatics. 26 (14): 1804–5. doi:10.1093/bioinformatics/btq264. PMC 2894509. PMID 20501551. 
• Zhu J, Zhu J, Negri A, Provasi D, Filizola M, Coller BS, Springer TA (2010). "Closed headpiece of integrin αIIbβ3 and its complex with an αIIbβ3-specific antagonist that does not induce opening". Blood. 116 (23): 5050–9. doi:10.1182/blood-2010-04-281154. PMC 3012599. PMID 20679525. 
• Provasi D, Filizola M (2010). "Putative active states of a prototypic g-protein-coupled receptor from biased molecular dynamics". Biophysical Journal. 98 (10): 2347–55. Bibcode:2010BpJ....98.2347P. doi:10.1016/j.bpj.2010.01.047. PMC 2872269. PMID 20483344. 
• Provasi D, Artacho MC, Negri A, Mobarec JC, Filizola M (2011). "Ligand-induced modulation of the free-energy landscape of G protein-coupled receptors explored by adaptive biasing techniques". PLoS Computational Biology. 7 (10): e1002193. Bibcode:2011PLSCB...7E2193P. doi:10.1371/journal.pcbi.1002193. PMC 3192824. PMID 22022248. 
• 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 (2011). "Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs". Cell. 147 (5): 1011–23. doi:10.1016/j.cell.2011.09.055. PMC 3255795. PMID 22118459. 
• Johnston JM, Aburi M, Provasi D, Bortolato A, Urizar E, Lambert NA, Javitch JA, Filizola M (2011). "Making structural sense of dimerization interfaces of delta opioid receptor homodimers". Biochemistry. 50 (10): 1682–90. doi:10.1021/bi101474v. PMC 3050604. PMID 21261298. 
• Johnston JM, Wang H, Provasi D, Filizola M (2012). "Assessing the relative stability of dimer interfaces in g protein-coupled receptors". PLoS Computational Biology. 8 (8): e1002649. doi:10.1371/journal.pcbi.1002649. PMC 3420924. PMID 22916005. 
• Filizola M, Devi LA (2012). "Structural biology: How opioid drugs bind to receptors". Nature. 485 (7398): 314–7. Bibcode:2012Natur.485..314F. doi:10.1038/485314a. PMC 3589518. PMID 22596150. 
• 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 (2012). "Structure-guided design of a high-affinity platelet integrin αIIbβ3 receptor antagonist that disrupts Mg²⁺ binding to the MIDAS". Science Translational Medicine. 4 (125): 125ra32. doi:10.1126/scitranslmed.3003576. PMC 3390238. PMID 22422993. 
• Negri A, Rives ML, Caspers MJ, Prisinzano TE, Javitch JA, Filizola M (2013). "Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening". Journal of Chemical Information and Modeling. 53 (3): 521–6. doi:10.1021/ci400019t. PMC 3702663. PMID 23461591. 
• Gomes I, Fujita W, Gupta A, Saldanha SA, Saldanha AS, Negri A, Pinello CE, Eberhart C, Roberts E, Filizola M, Hodder P, Devi LA (2013). "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. 110 (29): 12072–7. Bibcode:2013PNAS..11012072G. doi:10.1073/pnas.1222044110. PMC 3718106. PMID 23818586. 
• Shang Y, LeRouzic V, Schneider S, Bisignano P, Pasternak GW, Filizola M (2014). "Mechanistic insights into the allosteric modulation of opioid receptors by sodium ions". Biochemistry. 53 (31): 5140–9. doi:10.1021/bi5006915. PMC 4131901. PMID 25073009. 
• Schneider, Sebastian; Provasi, Davide; Filizola, Marta (2015). "The Dynamic Process of Drug-GPCR Binding at Either Orthosteric or Allosteric Sites Evaluated by Metadynamics". In Filizola, Marta. G Protein-Coupled Receptors in Drug Discovery. Methods in Molecular Biology. 1335. pp. 277–94. doi:10.1007/978-1-4939-2914-6_18. ISBN 978-1-4939-2913-9. PMC 4703114. PMID 26260607. 
• Provasi D, Boz MB, Johnston JM, Filizola M (2015). "Preferred supramolecular organization and dimer interfaces of opioid receptors from simulated self-association". PLoS Computational Biology. 11 (3): e1004148. Bibcode:2015PLSCB..11E4148P. doi:10.1371/journal.pcbi.1004148. PMC 4379167. PMID 25822938. 
• 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 (2015). "Discovery, synthesis, and molecular pharmacology of selective positive allosteric modulators of the δ-opioid receptor". Journal of Medicinal Chemistry. 58 (10): 4220–9. doi:10.1021/acs.jmedchem.5b00007. PMC 4703104. PMID 25901762. 

References

External links

• Filizola Laboratory