Ruth Matesanz Address:

Calle Doctor Pichardo, 5 bajo izq E-40001 Segovia (Spain) Phone: +34 609 25 78 40 e-mail: [email protected] Nationality: Spanish Date of birth: 3rd March 1976 Place of birth: Málaga (Spain)

Education

2009 Universidad Autónoma de Madrid Ph. D. in Molecular Biology

Spain

Title: "Optimization of the microtubule-taxol interaction: design of high affinity taxanes"

2001 Universidad Autónoma de Madrid M. Sc. in Molecular Biology

Spain

1999 Universidad Autónoma de Madrid B. Sc. in Biological Sciences

Spain

Speciality in Biochemistry and Molecular Biology

Languages

Spanish: mother language English: spoken and written German: spoken and written French: basic skill Italian: basic skill Arabic: introductory course

Research experience

February 2009-current Centro de Investigaciones Biológicas. Madrid (Spain) Postdoctoral research • Microtubules stabilizing agents group. 2005-2009 Centro de Investigaciones Biológicas. Madrid (Spain) Predoctoral Trainee • On the subject: Interaction of the tubulin regulatory sites with their activating ligands. 2003-2005 Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria. Madrid (Spain) Graduate research • On the subject: Increasing the potency of vaccinia MVA vaccines. 1999-2004 Instituto Cajal de Neurobiología. Madrid (Spain) Graduate research • On the subject: Asymmetric cell division and lateral inhibition in neural differentiation and fenotypic acquisition. 1995-1999 Undergraduate research

Instituto Cajal de Neurobiología Madrid (Spain)

• On the subject: Differentiation of retinal ganglion cells in the chick retina.

Fellowships

• 2004/2005: Predoctoral fellowship I.N.I.A. Spanish Ministry of Science and Technology. • June 2000/December 2003: Predoctoral fellowship F.P.I. Spanish Ministry of Science and Technology. • October 2000: Short-term fellowship at Max-Planck Institut für Hirnforschung , Frankfurt am Main (Germany) Laboratory of Prof. Dr. Hermann Rohrer

Publications

1.- I. Suarez, R. Matesanz, I. Aguirre de Cárcer, P.L. Pernas, F. Jaque , R. Blasco and G. Lifante . “Antibody binding on LiNbO3:Zn waveguides for sensor applications" Sensors & Actuators B: Chemical. 107 (2005) 88-92. 2.- Rubén M. Buey, Enrique Calvo, Isabel Barasoain, Oriol Pineda, Michael C. Edler, Ruth Matesanz, Gemma Cerezo, Christopher D. Vanderwal, Billy W. Day, Erik J. Sorensen, Juan Antonio López, José Manuel Andreu, Ernest Hamel, and J. Fernando Díaz. “Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites” Nature Chemical Biology. 3(2) (2007) 117-25 3.- Yang CG, Barasoain I, Li X, Matesanz R, Liu R, Sharom FJ, Yin DL, Diaz JF, Fang WS. “Overcoming Tumor Drug Resistance with High-Affinity Taxanes: A SAR Study of C2-Modified 7-Acyl-10-Deacetyl Cephalomannines.” ChemMedChem. 2(5) (2007) 691701 4.- Wang L, Alcaraz AA, Matesanz R, Yang CG, Barasoain I, Diaz JF, Li YZ, Snyder JP, Fang WS. ”Synthesis, biological evaluations, and tubulin binding poses of C-2alpha sulfur linked taxol analogues.” Bioorganic & Medicinal Chemistry Letters. 17(11) (2007) 3191-4 5.- Giuseppe La Regina, Michael C. Edler, Andrea Brancale, Sahar Kandil, Francesco Piscitelli, Ernest Hamel, Gabriella De Martino, Ruth Matesanz, José Fernando Díaz, Anna Ivana Scovassi, Ennio Prosperi, Antonio Lavecchia, Ettore Novellino, Marino Artico, and Romano Silvestri. “New Arylthioindoles Inhibitors of Tubulin Polymerization. 3. Biological Evaluation, Structure-Activity Relationships and Molecular Modeling Studies”. Journal of Medicinal Chemistry. 50(12) (2007) 2865-74 6.- Jorge García-Fortanet, Juan Murga, Miguel Carda, and J. Alberto Marco, Ruth Matesanz, Isabel Barasoain, and J. Fernando Díaz. “The Total Synthesis and Biological Properties of the Cytotoxic Macrolides FD-891 and Its Non-natural (Z)-C12 isomer” Chemistry: A European Journal. 13(18) (2007) 5060-74 7.- Canales A, Matesanz R, Gardner NM, Andreu JM, Paterson I, Díaz JF, JiménezBarbero J. "The Bound Conformation of Microtubule-Stabilizing Agents: NMR Insights into the Bioactive 3D Structure of Discodermolide and Dictyostatin". Chemistry: A European Journal. 14(25) (2008) 7557-69 8.- Ruth Matesanz, Isabel Barasoain, Chun-Gang Yang, Lei Wang, Xuan Li, Concepción de Inés, Claire Coderch, Federico Gago, Jesús Jiménez Barbero, José Manuel Andreu, Wei-Shuo Fang and José Fernando Díaz. "Optimization of Taxane Binding to Microtubules: Binding Affinity Dissection and Incremental Construction of a HighAffinity Analog of Paclitaxel". Chemistry & Biology. 15 (2008) 573-85. 9.- Xuan Li, Isabel Barasoain, Ruth Matesanz, J. Fernando Díaz and Wei-Shuo Fang. "Synthesis and biological activities of high affinity taxane-based fluorescent probes". Bioorganic & Medicinal Chemistry Letters. 19 (2009) 751-54. 10.- Dietrich SA, Lindauer R, Stierlin C, Gertsch J, Matesanz R, Notararigo S, Díaz JF, Altmann KH. "Epothilone Analogues with Benzimidazole and Quinoline Side Chains: Chemical Synthesis, Antiproliferative Activity, and Interactions with Tubulin". Chemistry: A European Journal. 15(39) (2009) 10144-57.

11.- Barasoain I, García-Carril AM, Matesanz R, Maccari G, Trigili C, Mori M, Shi JZ, Fang WS, Andreu JM, Botta M, Díaz JF. "Probing the pore drug binding site of microtubules with fluorescent taxanes: evidence of two binding poses." Chemistry & Biology. 17(3) (2010) 243-53 12.- Ruth Matesanz, Benet Pera and J. Fernando Díaz. “Thermodynamics as a Tool for the Optimization of Drug Binding” Thermodynamics - Interaction Studies - Solids, Liquids and Gases (2011) ISBN: 978-953-307-563-1, InTech. 13.- Calvo E, Barasoain I, Matesanz R, Pera B, Camafeita E, Pineda O, Hamel E, Vanderwal CD, Andreu JM, Lopez JA, Díaz JF. "Cyclostreptin derivatives specifically target cellular tubulin and further map the paclitaxel site.” Biochemistry. 51(1) (2012) 329-41. 14.- Matesanz R, Rodríguez-Salarichs J, Pera B, Canales A, Andreu JM, JiménezBarbero J, Bras W, Nogales A, Fang WS, Díaz JF. “Modulation of microtubule interprotofilament interactions by modified taxanes.” Biophysical Journal. 101(12) (2011) 2970-80. 15.- Ruth Matesanz, José Fernando Diaz, Francisco Corzana, Andrés G. Santana, Agatha Bastida and Juan Luis Asensio. “Multiple keys for a single lock: the unusual structural plasticity of the Nucleotidyltransferase (4’)/kanamycin complex” Chemistry: A European Journal. (2012) doi: 10.1002/chem.201101888 Congress communications

• I. Aguirre de Cárcer, R.Matesanz, R. Blasco, I. Suarez, P.L. Pernas, F. Jaque and G. Lifante. “Antibody binding on LiNbO3:Zn waveguides for biosensor applications.” Europt(r)ode VII - 7th European Conference on Optical Chemical Sensors and Biosensors. 2004 Madrid, Spain • E.Turiegano, S. Sanchez-Pages, P. Regueira, R. Matesanz, J. Benito, L.Torroja and I.Canal. "Does she choose?:An statistical approach” 10th European symposium on Drosophila Neurobiology 2004 Neuchâtel, Switzerland. • Ruth Matesanz, Isabel Barasoain, Frances J. Sharom, José Manuel Andreu, Weishuo Fang, y J. Fernando Díaz. "Termodinámica de la interacción proteína-ligando aplicada a la optimización de fármacos. Modulación de la afinidad de los taxoides por su sitio en la tubulina como estrategia para vencer la resistencia múltiple a drogas". Reunión de la Red Temática Nacional “Estructura y Función de Proteínas” 2006 Bilbao, Spain • Rubén M. Buey, Enrique Calvo, Isabel Barasoain, Oriol Pineda, Michael C. Edler, Ruth Matesanz, Gemma Cerezo, Christopher D. Vanderwal, Billy W. Day, Erik J. Sorensen, Juan Antonio López, José Manuel Andreu, Ernest Hamel, y J. Fernando Díaz. "La interacción covalente de cicloestreptina con la β-tubulina marca el camino de entrada del taxol a los microtúbulos." Reunión de la red temática “Estructura y Función de Proteínas” 2006 Bilbao, Spain • Rubén M. Buey, Enrique Calvo, Isabel Barasoain, Oriol Pineda, Michael C. Edler, Ruth Matesanz, Gemma Cerezo, Christopher D. Vanderwal, Billy W. Day, Erik J. Sorensen, Juan Antonio López, José Manuel Andreu, Ernest Hamel, y J. Fernando Díaz. "A chemical proteomics approach reveals the taxoid binding to microtubules". 7th Proteomics Meeting 2006 Siena, Italy. • J. Fernando Díaz, Rubén M. Buey, Begoña Monterroso, Benet Pera, Ruth Matesanz, Noemí Bustamante, Pablo Chacón, Juan Antonio Hermoso, Margarita Menéndez. "Insights into Molecular Plasticity of Choline Binding Proteins (Pneumococcal Surface Proteins) by SAXS". II Workshop on Applications of Synchrotron Light to NonCrystalline Diffraction in Materials and Life Sciences. 2007 Madrid, Spain

• Ruth Matesanz, Isabel Barasoain, Chung-Gang Yang, Lei Wang, Xuan Li, Concepción de Inés, Claire Coderch, Federico Gago, Jesús Jiménez Barbero, José Manuel Andreu, Wei-Shuo Fang and José Fernando Díaz. "Optimization of taxane binding to microtubules.Binding affinity dissection and incremental construction of a high-affinity analogue of paclitaxel." 1st Portuguese-Spanish-British Joint Biophysics Congress 2008. Lisbon, Portugal. • E Buzamet, N Bustamante, R Matesanz, H Kaltner, JL Saiz, M Menéndez, F Díaz, H_J Gabius, D Solís. "T16-30 estudio de la organización estructural de la galectina-4 humana". XXXI Congreso de la Sociedad Española de Bioquímica y Biología Molecular. 2008 Bilbao, Spain

• Enrique Calvo, Emilio Camafeita, Benet Pera, Ruth Matesanz, Isabel Barasoain, Fernando Díaz, J.A. López. "Chloroacetylation of cyclostreptin influences its interaction with tubulin". III Congreso de la Sociedad Española de Proteómica. 2009 Pamplona, Spain. • R. Matesanz, B. Pera, A. Nogales, J.F. Díaz. "Alteraciones de la estructura de los microtúbulos en respuesta a modificaciones en la molécula de paclitaxel". XXXII Congreso de la Sociedad Española de Bioquímica y Biología Molecular. 2009 Oviedo, Spain. • Ruth Matesanz, Benet Pera, Aurora Nogales, José Fernando Díaz. "Alteraciones de la estructura de los microtúbulos en respuesta a modificaciones en la molécula de paclitaxel". VI Reunión de la Red Temática Nacional “Estructura y Función de Proteínas” 2010 Madrid, Spain. • Isabel Barasoain, Ana M. García-Carril, Ruth Matesanz, Giorgio Maccari, Chiara Trigili, Mattia Mori, Jing-Zhe Shi, Wei-Shuo Fang, José M. Andreu, Maurizio Botta and J. Fernando Díaz. "Probing the pore drug binding site of microtubules with fluorescent taxanes: Evidence of two binding poses". VI Reunión de la Red Temática Nacional “Estructura y Función de Proteínas” 2010 Madrid, Spain. • Ruth Matesanz, Fabian Feyen, Karl-Heinz Altmann and J. Fernando Díaz. "Molecular recognition of azathilones by microtubules". IV Spanish Portuguese Biophysical Congress. 2010 Zaragoza, Spain. • Isabel Barasoain, Ana M. García-Carril, Ruth Matesanz, Giorgio Maccari, Chiara Trigili, Mattia Mori, Jing-Zhe Shi, Wei-Shuo Fang, José M. Andreu, Maurizio Botta and J. Fernando Díaz. "Probing the pore drug binding site of microtubules with fluorescent taxanes: Evidence of two binding poses". IV Spanish Portuguese Biophysical Congress. 2010 Zaragoza, Spain. • Ruth Matesanz, Javier Rodríguez-Salarichs, Benet Pera, Ángeles Canales, José Manuel Andreu, Jesús Jiménez-Barbero, Wim Bras, Aurora Nogales, Wei-Shuo Fang, José Fernando Díaz. “Modulación de las interacciones entre protofilamentos de los microtúbulos por taxanos modificados”. XI Congreso de la Sociedad de Biofísica de España. 2011 Murcia, Spain. Experience in different techniques

- Molecular biology: PCR, cloning, electrophoresis, DNA probes labelling with 32P and DIG, Screening, RNA probes labelling, RNA and DNA isolation, cDNA synthesis, Tvectors construction for PCR fragments cloning, sequentiation, genetic manipulation with retroviral vectors, comparative PCR - Protein biochemistry: purification: centrifugation and ultracentrifugation; dyalisis; chromatography, electrophoresis, FPLC, HPLC; Western blot; colorimetry, densitometry - Cellular cultures: primary, cell lines, organotypic explants and slides

- Microscopy: electronic, light, fluorescence and confocal. - Histology: cryostate, microtome and vibrotome, immunohistochemistry, in situ hybridization, TUNEL labelling - Experimental embryology manipulations. - Virology: Vaccinia virus manipulation: stocks production, titulation, purification, recombinants production. - Immunology: ELISA, spleenocytes culture and stimulation, intracelular cytokines staining, flow cytometry - Biophysics: Fluorescence, absorption spectrophotometry, synchrotron X-ray scattering, automatic calculation and data processing, stopped-flow Use of large facilities

Synchrotron of the Science and Engineering Research Council, Daresbury, UK. European Synchrotron Radiation Facility, Grenoble, France. Bruker AXS NANOSTAR

Teaching experience

- Doctoral course “Neural basis of behaviour” collaboration. Department of Biology, Universidad Autónoma de Madrid. Academic year 2002/2003 - "Master of Bioinformatis" collaboration. Universidad Complutense de Madrid. Academic years 2006/2007; 2007/2008 y 2008/2009.

Other skills

- Finalist in the contest of ideas "Bioemprendedor Ibérico” 2002 Formation course 4th -5th October 2002 in Taguspark (Lisbon, Portugal). - Curso “Técnicas de Separación (LC y CE) acopladas a la espectrometría de masas. Aplicación a compuestos de bajo peso molecular.” dentro de las 11ªs Jornadas de Análisis Instrumental organizadas por la Sociedad Española de Química Analítica (14th November 2005) - Summer School in Synchrotron Radiation Science. Chester College & Daresbury Laboratory. (29th August-8th September 2006) - Visitor at Professor Wei-Shuo Fang laboratory in the Institute of Materia Medica in Beijing, China. (17th June-1st July 2007) - Technical note Applied Biosystems. Single Platform, Multi-Tiered Strategy to Reveal Cyclostreptin Binding Sites in Microtubules.Targeted Detection and Quantification using Precursor Ion Scanning and Multiple Reaction Monitoring with the 4000 QTRAP System. Enrique Calvo, Rubén M. Buey, Isabel Barasoain, Oriol Pineda, Michael C. Edler, Ruth Matesanz, Gemma Cerezo, Christopher D. Vanderwal, Billy W. Day, Erik J. Sorensen, José Manuel Andreu, Ernest Hamel, J. Fernando Díaz, Juan Antonio López. - EMBO Practical Course. Transient Kinetic Methods Applied to Biological Macromolecules in the School of Biosciences at the University of Kent. (27th June-3rd July 2010) - Workshop on docking and virtual screening: use of computational tools for drug design. Summer school, Universidad de Alcalá. (20th-22th June 2011)