Ph. D. Chemical Physics (1984) Yale University
M. Sc., M. Phil. Chemistry (1982) Yale University
Licenciado Mathematics (1980) Universidad Nacional del Sur, Argentina
Molecular Bioengineering; Statistical Physics; Algebra and Representation Theory; Chemical Physics; Molecular Biophysics; Bioinformatics; Computational Biology; Dehydron Theory; Clinical Kinomics; Medicinal Chemistry; Molecular Theranomic Engineering.
Email: arifer@rice.edu
Phone: 713-348-3681
Office: George R. Brown Hall, - Room E100B
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Ariel Fernandez
Karl F. Hasselmann Professor of Bioengineering
Karl F. Hasselmann Chair in Engineering Professor of Bioengineering Adjunct Professor of Computer Science, The University of Chicago Adjunct Professor of Molecular Therapy, University of Texas - M. D. Anderson Cancer Center Consultant, Eli Lilly and Company Honorary Member, Collegium Basilea, Switzerland Prof. Ariel Fernandez was originally trained in Chemistry and Mathematics and started a career in Algebra and Representation Theory. His current interests are centered in Molecular Biophysics, specifically in cooperativity and many body problems associated with protein folding, protein interactions and derived pharmacological problems. He introduced the category of structural wrapping and established its importance in the contexts of network centrality, molecular disease, drug discovery and molecular theranostic engineering. Some biotechnological implications of the wrapping concept are described in the following contributions: Ariel Fernandez: "Keeping Dry and Crossing Membranes". Nature Biotechnology 22, 1081-1084 (2004) Ariel Fernandez et al.: "Taming the induced folding of drug-targeted kinases". Trends in Pharmacological Sciences 30, 66-71 (2009) Jianping Chen, Xi Zhang and Ariel Fernandez: Molecular basis for specificity in the druggable kinome: sequence-based analysis. Bioinformatics 23, 563-572 (2007) Ariel Fernandez et al.: "Rational drug redesign to overcome drug resistance in cancer therapy: imatinib moving target". Cancer Research 67, 4028-4033, Priority Report, Cover Featured (2007) Ariel Fernandez et al.: "An anticancer C-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic". Journal of Clinical Investigation 117, 4044-4054 (2007) This contribution is placed in perspective in the accompanying Commentary by George Demetri: "Structural reengineering of imatinib to decrease cardiac risk in cancer therapy". Journal of Clinical Investigation 117, 3650-3653 (2007) Alejandro Crespo and Ariel Fernandez: "Kinase packing defects as drug targets". Drug Discovery Today 12, 917-923 (2007) His current research interests are focused on understanding how proteins may enhance their interactivity and diversify functionalities while preserving their folds. In this regard, his contributions to systems biology stem from a physico-chemical background. His most recent publications along these lines are Ariel Fernandez: "Functionality of wrapping defects in soluble proteins: What cannot be kept dry must be conserved". Journal of Molecular Biology 337, 477-484 (2004) Ariel Fernandez, L. Ridgway Scott and R. Stephen Berry: "The nonconserved wrapping of conserved folds reveals a trend towards increasing connectivity in proteomic networks". Proceedings of the National Academy of Sciences, USA 101, 2823-2827 (2004) Ariel Fernandez and R. Stephen Berry: "Molecular dimension explored in evolution to promote proteomic complexity". Proceedings of the National Academy of Sciences, USA 101, 13460-13465 (2004) Florin Despa, Ariel Fernandez and R. Stephen Berry: Dielectric modulation of biological water. Physical Review Letters 93, 228104 (4 pages) (2004); Featured in Nature (News and Views) 432, 688 (2004) Ariel Fernandez has also introduced the paradigm of "inhibitor as a wrapper of packing defects in proteins", a concept of potential importance in drug discovery. Some of his recent contributions in this realm are: Ariel Fernandez, Kristina Rogale, Ridgway Scott and Harold A. Scheraga: "Inhibitor design by wrapping packing defects in HIV-1 proteins", Proceedings of the National Academy of Sciences USA 101, 11640-11645 (2004). Ariel Fernandez: "Incomplete Protein Packing as a Selectivity Filter in Drug Design", Structure 13, 1829-1836 (2005) Education M. Sc., M. Phil., Ph. D., Yale University, 1982-1984 (fastest awarded Ph. D. in Yale history). Sr. Research Scientist, Max-Planck-Institut fuer biophysikalische Chemie, Abteilung Manfred Eigen, Goettingen, Germany, 1986-1989. Ariel Fernandez has contributed to a wide spectrum of research areas: Abstract Algebra, Representation Theory, Statistical Mechanics, Chemical Physics, Polymer Physics, Dissipative Systems, Molecular Biophysics, Structural Biology, Medicinal Chemistry, Clinical Kinomics and Integrative Biology. He performs and reports theoretical and experimental work. Some honors and positions Chair of "Resistance and Safety" session, Discovery on Target: Cambridge Healthtech Institute's Second Annual KINASE INHIBITORS Congress; October 20-23, Boston, MA, USA. Honorary Member, Collegium Basilea, Institute of Advanced Study, Basel, Switzerland Elected Fellow, American Institute for Medical and Biological Engineering (2006) Editor, Encyclopedia of Bioscience, Frontiers in Bioscience (2006-) National Cancer Institute (NCI) Reviewer. NIH Study Section RFA-07-005 "Advanced Proteomic Platforms and Computational Sciences for NCI Clinical Proteomic Technologies Initiative" (2006-) Camille and Henry Dreyfus Teacher-Scholar Awardee (1991) Camille and Henry Dreyfus Distinguished New Faculty Awardee (1989) John S. Guggenheim Memorial Foundation Fellow (1995-1996) Consultant to U.S. Federal Government, NIH, Special Panel on Centers of Excellence in Systems Biology (2003- ) Eli Lilly Unrestricted Grantee (2004) Professor, School of Informatics, Indiana University (2003-2005) Professor, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine (2003-2005) Visiting Senior Researcher, Max-Planck-Institut fuer Biochemie, Abteilung Robert Huber, Martinsried, Germany (2000- ) Editorial Board Member, Journal of Biological Physics and Chemistry, Basel, Switzerland (2000-) Guest Professor, Institute for Protein Research, Osaka University, Japan (2003) Medal "State of Buenos Aires" to the best graduate, Argentina (1980) Co-organizer and Proceedings Editor of the Miami Bio/Technology Winter Symposium, Nature-sponsored (1993) Selected recent publications (from a total of 312). 0. Ariel Fernandez: "Almost-Split Sequences and Morita Duality". Bulletin des Sciences Mathematiques, 2me. series 110, 425-435 (1986) 1. Ariel Fernandez: "Keeping Dry and Crossing Membranes". Nature Biotechnology 22, 1081-1084 (2004). 2. Ariel Fernandez: "Functionality of wrapping defects in soluble proteins: What cannot be kept dry must be conserved". Journal of Molecular Biology 337, 477-483 (2004). 3. Ariel Fernandez, L. Ridgway Scott and R. Stephen Berry: "The nonconserved wrapping of conserved folds reveals a trend towards increasing connectivity in proteomic networks". Proceedings of the National Academy of Sciences, USA 101, 2823-2827 (2004). 4. Ariel Fernandez, Kristina Rogale, L. Ridgway Scott and Harold A. Scheraga: "Inhibitor design by wrapping packing defects in HIV-1 proteins". Proceedings of the National Academy of Sciences, USA 101, 11640-11645 (2004). 5. Ariel Fernandez and Harold A. Scheraga: "Insufficiently dehydrated hydrogen bonds as determinants for protein interactions", Proceedings of the National Academy of Sciences, USA 100, 113-118 (2003). 6. Ariel Fernandez and R. Stephen Berry: "Proteins with hydrogen-bond packing defects are highly interactive with lipid bilayers: Implications for amyloidogenesis", Proceedings of the National Academy of Sciences, USA 100, 2391-2396 (2003). 7. Ariel Fernandez and Ridgway Scott: "Adherence of packing defects in soluble proteins", Physical Review Letters 91, 018102, 4 pages (2003). 8. Ariel Fernandez, Jozsef Kardos, Ridgway Scott, Yuji Goto and R. Stephen Berry: "Structural defects and the diagnosis of amyloidogenic propensity", Proceedings of the National Academy of Sciences,USA 100, 6446-6451 (2003). 9. Ariel Fernandez: "Direct nanoscale dehydration of hydrogen bonds". Journal of Physics D: Applied Physics 38, 2928-2932 (2005). 10. Ariel Fernandez: "Incomplete protein packing as a selectivity filter in drug design". Structure 13, 1-8 (2005)
Selected Publications
Abstract
Ariel Fernandez "The Lagrangian Structure of Long-time Torsional Dynamics Leading to RNA Folding." Journal of Statistical Physics, 92 (1998): 237-255.
Fernandez and Ridgway Scott "Adherence of packing defects in soluble proteins." Physical Review Letters, 91 (2003): 018102.
Ariel Fernandez "What caliber pore is like a pipe? Nanotubes as modulators of ion gradients." Journal of Chemical Physics, 119 (2003): 5315-5319.
Ariel Fernandez "Buffering the entropic cost of hydrophobic collapse in folding proteins." Journal of Chemical Physics, 121 (2004): 11501-11503.
Ariel Fernandez "Functionality of wrapping defects in soluble proteins: What cannot be kept dry must be conserved." Journal of Molecular Biology, 337 (2004): 477-483.
Ariel Fernandez "Keeping Dry and Crossing Membranes." Nature Biotechnology, 22 (2004): 1081-1084.
Ariel Fernandez and Kristina Rogale "Sequence space selection of cooperative model proteins." Journal of Physics A: Math. Gen., 37 (2004): 197-202.
Article
Ariel Fernandez, Alejandro Crespo, Sridhar Maddipati and Ridgway Scott: "Bottom-up engineering of peptide cell translocators based on environmentally modulated
quadrupole switches." ACS Nano, 2 (2008): 61-68.
Han Liang and Ariel Fernandez "Evolutionary constraints imposed by gene dosage
balance." Frontiers in Bioscience, 13 (2008): 4373-4378.
Ariel Fernandez, Xi Zhang and Jianping Chen "Folding and wrapping soluble
proteins: Exploring the molecular basis of cooperativity and aggregation
." Progress in Nucleic Acids Research and Molecular Biology, 83 (2008): 57-87.
Xi Zhang and Ariel Fernandez "In silico drug profiling of the human kinome based
on a molecular marker for cross reactivity." Molecular Pharmaceutics (ACS), 5 (2008): 728-738.
Alejandro Crespo and Ariel Fernandez "Induced disorder in protein-ligand complexes
as a drug-design strategy." Molecular Pharmaceutics (ACS), 5 (2008): 430-437.
Jianping Chen, Han Liang and Ariel Fernandez "Protein structure protection commits
gene expression patterns." Genome Biology, 9 (2008): R107.
Han Liang, Kristina Rogale-Plazonic, Jianping Chen, Wen-Hsiung Li and Ariel Fernandez "Protein under-wrapping causes dosage sensitivity and decreases gene duplicability." PLoS Genetics, 4 (2008): e11.
Ariel Fernandez and Alejandro Crespo "Protein wrapping: a marker for association,
aggregation and molecular targeted therapy." Chemical Society Reviews (Royal Society of Chemistry, UK) , Tutorial Review, 37 (2008): 2373-2382.
Alejandro Crespo, Xi Zhang and Ariel Fernandez "Redesigning kinase inhibitors to
enhance specificity." Journal of Medicinal Chemistry, 51 (2008): 4890-4898.
Ariel Fernandez "What factor drives the fibrillogenic association of beta-sheets?." FEBS Letters (Fed. Eur. Biochem. Soc.), 579 (2005): 6635-6640.
Ariel Fernandez "The integrated development of network complexity modulates the diverse evolutionary mutation rates of individual proteins." FEBS Letters (Fed. Eur. Biochem. Soc.), 579 (2005): 5718-5722.
Ariel Fernandez "Protein function with concurrent promiscuity." Opinions and Commentary, Journal of Biomolecular Structure & Dynamics, 22 (2005): 615-624.
Ariel Fernandez "Incomplete protein packing as a selectivity filter in drug design." Structure, 13 (2005): 1829-1836.
Ariel Fernandez "Direct nanoscale dehydration of hydrogen bonds." Journal of Physics D: Appl. Phys., 38 (2005): 2928-2932.
Ariel Fernandez, Soledad Bazan and Jianping Chen: Taming the induced folding of drug-targeted kinases. Trends in Pharmacological Sciences 30, 66-71 (2009)
Book chapter
Vladimir N. Uversky, Ariel Fernández and Anthony L. Fink "Structural and conformational prerequisites of amyloidogenesis In: Protein Misfolding, Aggregation and Conformational Diseases. Vol. I: Protein Aggregation and Conformational Diseases." (2006): 1-20.
Conference paper
Ariel Fernandez, R. Stephen Berry "Molecular dimension explored in evolution to promote proteomic complexity." Proceedings of the National Academy of Sciences, USA, 101 (2004): 13460-13465.
Other
Ariel Fernandez, Xi Zhang and Jianping Chen "Folding and wrapping soluble proteins: Exploring the molecular basis of cooperativity and aggregation
." Progress in Nucleic Acids Research and Translational Science, 83 (2008): 57-87.
Ariel Fernandez "Structural Phase Transitions and the Catalytic Role of RNA in Proton Transfer Events." Naturwissenschaften, 76 (1989): 469-473.
Refereed Article
Ariel Fernandez, Jianping Chen and Alejandro Crespo, "Solvent-exposed backbone
loosens the hydration shell of soluble folded proteins." Journal of Chemical Physics, 126 (2007): 245103.
Ariel Fernandez et al., "Rational drug redesign to overcome drug resistance in cancer therapy:
imatinib moving target." Cancer Research/Priority Report/Issue Cover, 67 (2007): 4028-4033.
Sridhar Maddipati and Ariel Fernandez, "Peptide translocators with engineered
dehydration-prone hydrogen bonds." Journal of Chemical Physics, 126 (2007): 061102.
Jianping Chen, Xi Zhang and Ariel Fernandez, "Molecular basis for specificity in
the druggable kinome: sequence-based analysis." Bioinformatics, 23 (2007): 563-572.
Alejandro Crespo and Ariel Fernandez, "Kinase packing defects as drug targets." Drug Discovery Today, 12 (2007): 917-923.
Keith Dunker and Ariel Fernandez, "Engineering productive enzyme confinement." Trends in Biotechnology, 25 (2007): 189.
Natalia Pietrosemoli, Alejandro Crespo and Ariel Fernandez, "Dehydration propensity of
order-disorder intermediate regions in soluble proteins." Journal of Proteome Research, 6 (2007): 3519-3526.
Jianping Chen, Han Liang and Ariel Fernandez, "Protein structure protection commits gene expression patterns." Genome Biology, 9 (2008): R107.
Ariel Fernandez et al., "A re-engineered anticancer C-Kit kinase inhibitor is more active and less cardiotoxic." Journal of Clinical Investigation, 117 (2007): 4044-4054.
Ariel Fernandez and Sridhar Maddipati "Feature-similarity kinase classifier as a ligand engineering tool." Biomolecular Engineering, 23 (2006): 307-15.
Ariel Fernandez and Sridhar Maddipati. "A priori inference of cross reactivity for drug-targeted kinases." Journal of Medicinal Chemistry, 49 (2006): 3092-3100.
Xi Zhang, Alejandro Crespo and Ariel Fernandez, "Turning promiscuous kinase inhibitors into safer drugs." Trends in Biotechnology, 26 (2008): 295-302.
Presentations
Keynote Speaker
"Society of Toxicology Annual Meeting." San Diego, CA. (October 2, 2008)
Lecture
"Discovery on Target 2007, Cambridge Healthtech Institute Kinase Inhibitors Conference." World Trade Center, Boston, MA. (October 15-18, 2007)
"Re-engineering of Imatinib to Decrease Cardiac Risk: Translational Ideas
in Drug Discovery." Cambridge Healthtech Institute Second Annual Cardiotoxicity and Drug Safety Conference, Philadelphia, PA. (May 12-13, 2008)
"7th International Workshop on Pharmacodynamics of Anticancer Agents, organized by
Mark Ratain (University of Chicago),." Guanacaste, Costa Rica. (September 16-20,)
"Curbing Side Effects in Anticancer Drugs." Science for Health with a Human Face International Symposium, Madrid, Spain. (November 4-7, 2008)
"Translational Ideas in Drug Discovery." Genomics Research Center, Academia Sinica, Taipei, Taiwan. (June 14-21, 2008)
Seminar Speaker
"Translational ideas in drug discovery." Academia Sinica, Genomics Research Center, Taipei. (June 14-21, 2008)
Session Chair
Lecturer and Chair. "Translational Ideas to Curb Side Effects in Anticancer Kinase-targeting Therapy: Reducing
Cardiotoxicity Through Inhibitor Redesign." Discovery on Target: Cambridge Healthtech Institute Second Annual KINASE INHIBITORS Conference, Boston, MA. (October 20-23, 2008)
Editorial Positions
Editor, Frontiers of Bioscience Encyclopaedia of Bioscience, (2007).
Member of the Editorial Board, Journal of Biological Physics and Chemistry, (2007).
Editor, Encyclopedia of Bioscience, (2008).
Editor, Frontiers in Bioscience, (2008).
Editor, Journal of Biological Physics and Chemistry, (2008).
Theses
Jianping Chen, Ph. D. "Molecular Basis for Gene Dosage Sensitivity." (2008).(Thesis or Dissertation Director)
Xi Zhang, Ph. D. . "Molecular Basis for Specificity in the Druggable Kinome." (2008).(Thesis or Dissertation Director)
Grants and Proposals
Protein packing defects as functional markers and drug targets (NIH/NIGMS award) PI: Ariel Fernandez, National Institutes of Health / National Institute of General Medical Sciences.
Computational discovery of selectivity filters for the pharmacokinome, PI: Ariel Fernandez, Gulf Coast Center for Computational Cancer Research/ John & Ann Doerr Fund.
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