OBJETIVOS

El Laboratorio de Farmacología y Oncología Molecular destina sus esfuerzos a la descripción y validación de nuevos blancos terapéuticos para el tratamiento del cáncer con el objetivo de desarrollar novedosos prototipos farmacológicos más selectivos y eficaces mediante diseño racional. El laboratorio realiza una importante traslación del conocimiento a diferentes grupos del sector científico nacional e internacional a través de colaboraciones académico-científicas. El fin último de dicho trabajo interdisciplinario es la traslación de conocimiento genuino y recursos humanos altamente calificados en bien de la salud pública, la educación pública y la ciencia y la tecnología nacional.

 

INTEGRANTES

CARLOS DAVIO

Profesor Titular de Farmacología, FFyB, UBA e Investigador Principal CONICET

AGUSTIN YANEFF

Investigador Adjunto CONICET

ANA SAHORES

Investigador Asistente CONICET

RAMIRO CERVIÑO

Becario Doctoral CONICET.

 

LINEAS DE INVESTIGACIÓN

RELEVANCIA DEL AMPC Y SU CASCADA DE SEÑALIZACIÓN  Y BALANCE AMPC-INTRACELULAR VS. AMPC-EXTRACELULAR EN LA PROGRESIÓN DEL CÁNCER: IMPLICANCIAS TERAPÉUTICAS Y DIRECCIONES FUTURAS.

La ciencia, la tecnología y el conocimiento en general, atraviesan todos los estratos de la vida cotidiana (economía, educación, salud, trabajo, bienes, servicios, etc.) constituyendo un poderoso instrumento para resolver problemáticas propias y permitir que el Estado pueda realizar de manera eficaz el diagnóstico, formulación y aplicación de políticas de alto impacto social o económico.

La validación de un blanco con fines traslacionales se inicia solo a partir de conocimiento previo. El proyecto que lidero postula a la cascada de transducción de señales del AMPc como blanco terapéutico en cáncer. El AMPc fue el primer segundo mensajero descripto, resultando determinante en el inicio de la era de la transducción de señales. Su descubridor, Sutherland premio Nobel de Medicina, a los pocos años del descubrimiento describió que el mismo era transportado al espacio extracelular por un mecanismo dependiente de energía. En la última década se comprendió el mecanismo molecular de transporte, mediado por la proteína de resistencia a multidrogras, MRP4. En los últimos años, la expresión de MRP4 se propuso como factor pronóstico de diferentes tipos de cáncer, asociado a oncogenes tradicionalmente predictores de la transformación maligna. El grupo de trabajo que dirijo ha descripto al MRP4 y su relación con la resolución temporal de la respuesta de AMPc asociado a los procesos de proliferación y diferenciación celular en cáncer. MRP4 debe considerarse asimismo como transportador de xenobióticos, muchos de ellos drogas antitumorales de uso en la clínica y endobióticos, no solo AMPc, sino también prostaglandinas y leucotrienos actores fundamentales en el proceso inflamatorio. La estabilidad del AMPc en plasma y su incremento descripto en procesos hiperproliferativos lo transforman en un candidato como biomarcador de prognosis y/o eficacia terapéutica, de fácil detección. Estudios recientes del grupo mediante análisis in sílico y resultados experimentales, junto a reportes en la literatura, muestran que en la regulación de la expresión de MRP4 convergen vías desreguladas en proliferación. La resolución temporal de la respuesta del AMPc no solo es consecuencia de la actividad de MRP4, sino que participan asimismo diferentes actores, receptores acoplados a proteínas G (GPCRs), proteínas G y fosfodiesterasas, entre otros. El propósito fundamental de la investigación consiste en realizar mediante un abordaje interdisciplinario un estudio integral de la cascada de señalización de AMPc y otras vías que convergen en la misma con el fin de validar a los componentes cruciales como candidatos a blancos para el desarrollo racional de fármacos. En el grupo de trabajo que dirijo forma parte de un consorcio de laboratorios que involucra profesionales de la biomedicina con diferentes experiencias: farmacólogos moleculares, químicos medicinales, biólogos moleculares, oncólogos moleculares, oncólogos clínicos, bio-estadistas, bio-informáticos, médicos patólogos, entre otros. Al presente nos encontramos trabajando en diferentes tipos de cáncer: Páncreas, Vesícula y Vías Biliares, Leucemias, Renal de células claras y mama.

 

PUBLICACIONES DE LOS ÚLTIMOS AÑOS

En revistas internacionales con referato

  1. The xenobiotic transporter ABCC4/MRP4 promotes epithelial mesenchymal transition in pancreatic cancer. Gancedo SN, Sahores A, Gómez N, Di Siervi N, May M, Yaneff A, de Sousa Serro MG, Fraunhoffer N, Dusetti N, Iovanna J, Shayo C, Davio CA, González B. Front Pharmacol. 2024 Jul 24;15:1432851. doi: 10.3389/fphar.2024.1432851
  2. Rosmarinic Acid Present in Lepechinia floribunda and Lepechinia meyenii as a Potent Inhibitor of the Adenylyl Cyclase gNC1 from Giardia lamblia. Zurita A, Vega Hissi E, Cianci Romero A, Luján AM, Salido S, Yaneff A, Davio C, Cobo J, Carpinella MC, Enriz RD. Plants (Basel). 2024 Feb 26;13(5):646. doi: 10.3390/plants13050646.
  3. Effect of bicarbonate and polyvinyl alcohol on in vitro capacitation and fertilization ability of cryopreserved equine spermatozoa. Arroyo-Salvo C, Río S, Bogetti ME, Plaza J, Miragaya M, Yaneff A, Davio C, Fissore R, Gervasi MG, Gambini A, Perez-Martinez S. Andrology. 2024 May 28. doi: 10.1111/andr.13667.
  4. La vacuna de ARNm para el tratamiento del cáncer de páncreas llegó para quedarse. Chuluyan E, Davio C, Dusetti N, Fraunhoffer N, Garcia MN, Garona J, González B, Gottardo F, Grasso D, Iovanna J, Kohan G, Lada PE, Mazza O, Monte M, Papademetrio D, Pasqualini ME, Sahores A, Santofimia P, Yaneff A. MEDICINA (Buenos Aires) 2023: 83: 650-652
  5. Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression. Rosenberg ML, Yaneff A, Ferradás GM, Villafañe Tapia MP, Davio CA, Goette NP, Vlachovsky SG, Peroni RN, Oddo EM, Azurmendi PJ. Life (Basel). 2023 Aug 28;13(9):1817. doi: 10.3390/life13091817.
  6. Chlorpromazine, an Inverse Agonist of D1R-Like, Differentially Targets Voltage-Gated Calcium Channel (CaV) Subtypes in mPFC Neurons. McCarthy CI, Mustafá ER, Cornejo MP, Yaneff A, Rodríguez SS, Perello M, Raingo J. Mol Neurobiol. 2023 Jan 25. doi:10.1007/s12035-023-03221-1.
  7. Functional alterations of two novel MC4R mutations found in Argentinian pediatric patients with early onset obesity. Fernández E, McCarthy CI, Cerviño RH, Rodríguez SS, Yaneff A, Hernández J, Garrido V, Di Rocco F, Raingo J. Mol Cell Endocrinol. 2023 Jan 1;559:111777. doi: 10.1016/j.mce.2022.111777.
  8. Endocrine therapy unleashes antitumor immunity preventing mammary tumor relapse and increasing immune checkpoint blockade sensitivity. Sequeira GR#, Sahores A#, Dalotto-Moreno T#, Vanzulli S, Polo ML, Radisky D, Novaro V, Pataccini G, Lamb CA, Salatino M*, and Lanari CL*. Cancer Res. 2021 Mar 1;81(5):1375-1387. DOI: 10.1158/0008-5472.CAN-20-1441.
  9. Rv2577 of Mycobacterium tuberculosis Is a Virulence Factor With Dual Phosphatase and Phosphodiesterase Functions. Forrellad MA, Blanco FC, Marrero Diaz de Villegas R, Vázquez CL, Yaneff A, García EA, Gutierrez MG, Durán R, Villarino A, Bigi F. Frontiers in Microbiology, 2020 Oct 22;11:570794. doi: 10.3389/fmicb.2020.570794.
  10. Ceefourin-1, a MRP4/ABCC4 inhibitor, induces apoptosis in AML cells enhanced by histamine. Sahores A, González AR, Yaneff A, May M, Gómez N, Monczor F, Fernández N, Davio C, Shayo C. Biochim Biophys Acta Gen Subj. 2023 Feb 9:130322. doi: 10.1016/j.bbagen.2023.130322. ISSN 0304-4165. IF2022: 4.12 – Q1 
  11. A Potent N-(piperidin-4-yl)-1H-pyrrole-2-carboxamide Inhibitor of Adenylyl Cyclase of lamblia: Biological Evaluation and Molecular Modelling Studies. Esteban Vega Hissi, Antonella de Costa Guardamagna, Adriana Garro, Cristian Falcon, Marko Anderluh, Tihomir Tomašič, Danijel Kikelj, Agustín Yaneff, Carlos Davio, Ricardo D. Enriz, Adolfo Zurita. Chem Med Chem 2021, doi: 10.1002/cmdc.202100037. ISSN 1860-7179. IF2020: 3.12 – Q1
  12. Biased agonism at histamine H1receptor: Desensitization, internalization and MAPK activation triggered by antihistamines. Burghi, V., Echeverría, E.B., Zappia CD, Díaz Nebreda A, Ripoll S,  Gómez N,  Shayo C, Davio C., Monczor, F., Fernández, N.C. J. of Pharmacol, 2021, 896, 173913. doi: 10.1016/j.ejphar.2021.173913. ISSN‎: ‎0014-2999 FI2018 3.09 - Q1
  13. MRP4/ABCC4 expression is regulated by histamine in acute myeloid leukemia cells, determining cAMP efflux. Angela Rodríguez González, Ana Sahores, Antonela Díaz-Nebreda, Agustín Yaneff, Nicolás Di Siervi, Natalia Gómez, Federico Monczor, Natalia Fernández, Carlos Davio, Carina Shayo. FEBS J. 2021. doi: 10.1111/febs.15344. ISSN‎: ‎ 1432-1033.FI201875 - Q1
  14. Cyclic AMP efflux through MRP4 regulates actin dynamics signaling pathway and sperm motilityin bovines. Chiarante N, Alonso CAI, Plaza J, Lottero R, Arroyo Salvo C, Yaneff A, Osycka-Salut C, Davio C, Miragaya M, Perez Martinez S. Sci Rep. 2020 10:15619. Doi: 10.1038/s41598-020-72425-5. ISSN 045-2322. IF2019: 3.998 – Q1
  15. Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer Sahores A, Carozzo A, May M, Gómez N, Di Siervi N, De Sousa Serro M, Yaneff A, Rodríguez-González A, Abba M, Shayo C, and Davio C. Sci Rep. 2020 10(1):14217. doi: 10.1038/s41598-020-71181-w.ISSN 045-2322. IF2019: 3.998 – Q1
  16. Multidrug resistance protein 4 (MRP4/ABCC4) is overexpressed in clear cell renal cell carcinoma (ccRCC) and is essential to regulate cell proliferation. Melana Colavita J., Todaro, J., de Sousa M., May, M., Gómez, N., Yaneff A., Di Siervi, N., Aguirre, M., Guijas C., Ferrini, L., Davio, C. Rodríguez, JP. Int J Biol Macromol. 2020, 161:836-847org/10.1016/j.ijbiomac.2020.06.106. ISSN 0141-8130. IF2019: 5.58 – Q1
  17. Fibronectin induces capacitation-associated events through the endocannabinoid system in bull Sperm. Osycka-Salut CE, Martínez-León E, Gervasi MG, Castellano L, Davio C, Chiarante N, Franchi AM, Ribeiro ML, Díaz ES, Perez-Martinez S. Theriogenology2020 153:91-101. doi: 10.1016/j.theriogenology.2020.04.031. ISSN‎: ‎ 0093-691X. FI20183 - Q1
  18. Constitutive activity of dopamine receptor type 1 (D1R) increases CaV2.2 currents in PFC neurons. McCarthy CI, Chou-Freed C, Rodríguez SS, Yaneff A, Davio C, Raingo J. J Gen Physiol. 2020 May 4;152(5):e201912492. doi: 10.1085/jgp.201912492. ISSN‎: ‎ ‎0022-1295 FI2018258 - Q1
  19. Agonist Effects of Propranolol on Non-Tumor Human Breast Cells. Lucía Gargiulo, Ezequiel Mariano Rivero, Nicolás di Siervi, Edgardo David Buzzi, Mariano Gabriel Buffone, Carlos Alberto Davio, Isabel Alicia Lüthy, Ariana Bruzzone. Cells 2020, 9, 1036; doi:10.3390/cells9041036. ISSN‎: ‎2073-4409 FI201865 - Q1
  20. The regulator of G protein signaling homologous domain of G protein-coupled receptor kinase 2 mediates short-term desensitization of β3-adrenergic receptor. Emiliana Beatriz Echeverria, Maia Cabrera, Valeria Burghi, Maximo Hernan Sosa, Sonia Ripoll, Agustín Yaneff, Federico Monczor, Carlos Alberto Davio, Carina Shayo, Natalia Cristina Fernandez. Front Pharmacol. 11:113. doi: 10.3389/fphar.2020.00113. eCollection 2020. ISSN‎: ‎1663-9812 FI2018 3.81 - Q1
  21. Inhibition of Endothelin system during the postnatal nephrogenic period in the rat. Its relationship with hypertension and renal disease in adulthood. Albertoni Borghese MF, Ortiz MDC, Marinoni RC, Oronel LH, Palamidessi M, Yarza CA, Di Siervi N, Davio C, Majowicz MP. Plos One, 2020, 15(3):e0229756. doi: 10.1371/journal.pone.0229756. ISSN 1932-6203 FI2019 99 - Q1
  22. Azelastine potentiates antiasthmatic dexamethasone effect on a murine asthma model. Carlos D. Zappia, Ariadna Soto, Gina Granja‐Galeano, Ignacio Fenoy, Natalia Fernandez, Carlos A. Davio, Carina Shayo, Carlos Fitzsimons, Alejandra Goldman, Federico Monczor. Pharmacol Res Perspect. 2019; e00531. doi.org/10.1002/prp2.531, ISSN 2052-1707 - Q1
  23. Identification of inhibitors of the RGS homology domain of GRK2 by docking-based virtual screening. Echeverría E, Velez Rueda AJ, Cabrera M, Juritz E, Burghi V, Fabián L, Davio C, Lorenzano Menna P, Fernández NC. Life Sciences 2019, 239: doi: 10.1016/j.lfs.2019.116872. ISSN 0024-3205 FI2018 3.448 - Q1
  24. Sphingosine 1-phosphate receptor 2/adenylyl cyclase/protein kinase A pathway is involved in taurolithocholate-induced internalization of Abcc2 in rats. Andermatten RB, Ciriaci N, Schuck VS, Di Siervi N, Razori MV, Miszczuk GS, Medeot AC, Davio CA, Crocenzi FA, Roma MG, Barosso IR, Sánchez Pozzi EJ. Arch Toxicol. 2019, 93(8):2279-2294, doi: 10.1007/s00204-019-02514-6. ISNN 340-5761; IF2018 728 Q1
  25. F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin.Gentile EA, Castronuovo CC, Cuestas ML, Gómez N, Davio C, Oubiña JR, Mathet VL. J Pharm Pharmacol. 2019 71(11):1655-1662. doi: 10.1111/jphp.13158. ISNN 2042-7158; IF2018 39 Q2
  26. Involvement of cAMP efflux, through MRP4 transporter, in the acquisition of fertilization ability of mouse spermatozoa. Alonso, CAI; Lottero Leconte, R; Luque, GM; Vernaz, Z; Di Siervi, N; Gervasi, MG; Buffone, MG; Davio, C; Perez Martinez, S. Journal of Cell Science, 2019, 132(14). pii: jcs230565, ISSN 1477-9137 FI2017 431 – Q1
  27. Identification of MRP4/ABCC4 as a Target for Reducing the Proliferation of Pancreatic Ductal Adenocarcinoma Cells by Modulating the cAMP Efflux. Carozzo A, Yaneff A, Gomez N, Di Siervi N, Sahores A, Diez F, Attorresi AI, Rodriguez-Gonzalez A, Monczor F, Fernandez N, Abba M, Shayo C, Davio C. Molecular Pharmacology, 2019, 96(1):13-25. doi: 10.1124/mol.118.115444. ISSN 0026-895X FI2017987 – Q1
  28. Metformin inhibits β-catenin phosphorylation on Ser-552 through an AMPK/PI3K/Akt pathway in colorectal cancer cells. Amable C., Martinez-Leon E., Pico ME., Di Siervi N., Davio C., Rozengurt E., Rey O. International Journal of Biochemistry and Cell Biology, 2019, 112:88-94. doi: 10.1016/j.biocel.2019.05.004.ISSN 1357-2725, FI2017247 – Q1
  29. Involvement of histamine H1and H2 receptor inverse agonists in receptor's crossregulation. Díaz Nebreda A, Zappia CD, Rodríguez González A, Sahores A, Sosa M, Burghi V, Monczor F, Davio C, Fernández N, Shayo C. Eur J Pharmacol. 2019, 847:42-52. doi: 10.1016/j.ejphar.2019.01.026. ISSN‎: ‎0014-2999 FI201809
  30. Participation of Gαi-Adenylate Cyclase and ERK1/2 in Mas Receptor Signaling Pathways. Burghi V, Echeverría EB, Sosa MH, Quiroga DT, Muñoz MC, Davio C, Monczor F, Fernández NC, Dominici FP. Front Pharmacol. 2019, 10:146. doi: 10.3389/fphar.2019.00146. ISSN‎: ‎1663-9812 FI201881
  31. MRP4/ABCC4 as a new therapeutic target: meta-analysis to determine substrate binding sites as a tool for drug design. Yaneff, A., Sahores, A., Gómez N., Carozzo A., Shayo C. and Davio C. Curr Med Chem., 2019;26(7):1270-1307. doi: 10.2174/0929867325666171229133259. ISSN 0929-8673 FI2016249
  32. Altered expression of Aquaporin-2 in one-kidney, one-clip hypertension. Albertoni Borghese MF., Hope S., Ortiz MC., Barchuk M., Kessler C., DavioC., Vatta M., Majowicz M. Life Sciences 2018, 208:72–78. ISSN 0024-3205 FI2018448.
  33. Unique pharmacological properties of serotonergic G-protein coupled receptors from cestodes. Camicia, F., Celentano, A.M., Johns, M.E., Chan, J.D., Maldonado, L., Vaca, H., Di Siervi, N., Kamentezky, L., Gamo, A.M., Ortega-Gutierrez, S., Martin-Fontecha, M., Davio, C., Marchant, S., and Rosenzvit, M. PLOS Neglected Tropical Diseases, 2018, 12(2):e0006267. doi: 10.1371/journal.pntd.0006267. ISSN 1935-2727 FI2016 3.834
  34. Synthesis and degradation of cAMP in Giardia lamblia: Possible role and characterization of a Nucleotidyl Cyclase with a single Cyclase-Homology-Domain. Vanina Saraullo, Nicolas Di Siervi, Belen Jerez, Carlos Davio, Adolfo Zurita. Biochem J., 2017. 474(23):4001-4017. doi: 10.1042/BCJ20170590. ISSN 0264-6021 FI2016 797
  35. Effect of mutation of Phe 24344 of the histamine H2 receptor on cimetidine mechanism of action. Granja-Galeano Gina, Zappia Carlos Daniel, Lucas Fabián, Davio Carlos, Shayo Carina, Fernández Natalia, Monczor Federico. Biochem Pharmacol., 2017. 146:117–126. doi: 10.1016/j.bcp.2017.09.014. ISSN 0006-2952 FI2016 4.581.
  36. Pharmacological Rac1 inhibitors with selective apoptotic activity in human acute leukemic cell lines. Cabrera M, Echeverria E, Remes Lenicov F, Cardama GA, Gonzalez N, Davio C, Fernández NC*, Lorenzano Menna P*. Oncotarget, 2017. doi: 10.18632/oncotarget.21533. ISSN 1949-2553 FI2016168.
  37. Extracellular cAMP activates molecular signalling pathways associated with sperm capacitation in bovines. Alonso CAI, Osycka-Salut C, Castellano L, Cesari A, Di Siervi N, Mutto A, Johannisson A, Morrell JM, Davio C, Perez-Martinez S. Mol Hum Reprod. 23(8):521-534, 2017 doi: 10.1093/molehr/gax030. ISSN 1360-9947 FI2016 3.585. (*) Davio C and Perez Martinez S.  contributed equally to the supervision and financial support of this study.
  38. Evidence for CB2 receptor involvement in LPS-induced reduction of cAMP intracellualar levels in uterine explants from pregnant mice: pathophysiological implications. Ana Inés Salazar, Alejandro Carozzo, Fernando Correa, Carlos Davio*, Ana María Franchi* Mol Hum Reproduction. 23(7):500-508, 2017. doi: 10.1093/molehr/gax026. ISSN 1360-9947 FI2016 585. (*) Carlos Davio and Ana Franchi contributed equally to the supervision and financial support of this study.
  39. Endogenous lysophosphatidic acid participates in vascularization and decidualization at the maternal-fetal interface in the rat. Micaela Sordelli, Jimena Beltrame, Elsa Zotta, Natalia Gomez, Ganna Dmytrenko, Maria Sales, Sandra Blois, Carlos Davio, Silvina Perez Martinez, Ana Franchi andMaria Ribeiro.   Reprod  Fertil Dev. doi: 10.1071/RD16235, ISSN 1031-3613, FI2016 2.656.
  40. Melanocortin 4 receptor constituvie activity inhibits L-type voltage-gated calcium channels in neurons. Agosti F, Cordisco Gonzalez S, Martinez Damonte V, Tolosa MJ, Di Siervi N, Schioth HB, Davio C, Perello M, Raingo J. Neuroscience, 2017. 346:102-112. doi: 10.1016/j.neuroscience.2017.01.007. ISSN 0306-4522, FI2016 277
  41. A Novel Effect of β-Adrenergic Receptor on Mammary Branching Morphogenesis and its Possible Implications in Breast Cancer. Gargiulo L, May M, Rivero EM, Copsel S, Lamb C, Lydon J,Davio C, Lanari C, Lüthy IA, Bruzzone A. J Mammary Gland Biol Neoplasia.  1:43-57. doi: 10.1007/s10911-017-9371-1. ISSN 1083-3021, FI2016 3.243
  42. Heparin exerts anti-apoptotic effects on uterine explants by targeting the endocannabioid system. Ana Inés Salazar, Claudia Vercelli,, Victoria Schiariti, Carlos Davio, Fernando Correa, Ana María Franchi. Apoptosis, 9:965-76, 2016, ISSN 1360-8185, FI2016 833
  43. PI3K pathway is involved in ERK signaling cascade activation by histamine H2R agonist in HEK293T cells. Alonso Natalia, Diaz Nebreda Antonela, Monczor Federico, Gutkind J. Silvio, Davio Carlos, Fernandez Natalia, Shayo Carina. BBA General Subjet, 1860:1998-2007, 2016, ISSN 0304-4165, FI2016 70
  44. Role of 3'-5'-cyclic adenosine monophosphate on the epidermal growth factor dependent survival in mammary epithelial cells. Diego Y. Grinman, Leonardo Romorini, Diego M. Presman, Luciana Rocha Viegas, Omar A. Coso, Carlos Davio, Adali Pecci. Mol Cell Endocrinol, ,419:259-267, 2016, ISSN 0303-7207 FI2016 754
  45. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways. Carlos Daniel Zappia, Gina Granja Galeano, Natalia Fernández, Carina Shayo, Carlos Davio, Carlos Fitzsimons, Federico Monczor. Rep. 5, 17476; doi:10.1038/srep17476, 2015, ISSN 2045-2322 FI2014 5.578
  46. G2/M cell cycle arrest and tumor selective apoptosis of acute leukemia cells by a promising benzophenone thiosemicarbazone compound. Cabrera M, Gomez N, Remes Lenicov F, Echeverría E, Shayo C, Moglioni A, Fernández N, Davio C. Plos One, 2015, 10(9): doi: 10.1371/journal.pone.013687. ISSN 1932-6203 FI2014 3.234
  47. Physiological implications of biased signaling at histamine H2 receptors.  Natalia Alonso, Carlos Daniel Zappia, Maia Cabrera, Carlos Davio, Carina Shayo, Federico Monczor, Natalia Cristina Fernandez. Pharmacol. 2015, 6:45. doi: 10.3389. ISSN:1663-9812. FI2014 3.80.
  48. Dual role of cAMP in the transcriptional regulation of multidrug resistance-associated protein 4 (MRP4) in pancreatic adenocarcinoma cell lines. Alejandro Carozzo, Federico Diez, Natalia Gomez, Maia Cabrera, Carina Shayo, Carlos Davio, Natalia Fernández. Plos One, 2015, 10(3): doi: 10.1371/journal.pone.0120651. ISSN 1932-6203 FI2014 3.234
  49. Blockade of multidrug resistance associated proteins aggravates acute pancreatitis and blunts atrial natriuretic factor beneficial effect in rats: Role of MRP4/ABCC4. María Silvia Ventimiglia, Ana Clara Najenson, Juan Carlos Perazzo,  Alejandro Carozzo,  Marcelo S. Vatta,  Carlos A. Davio*, Liliana G. Bianciotti*.  Mol Med. 2015, 21:58-67 doi: 10.2119 ISSN 1076-1551 FI2014508 *contributed equally to this study.
  50. Differential β2-adrenergic receptor expression defines the phenotype of non-tumorigenic and malignant human breast cell lines. L Gargiulo#, S Copsel#, E M Rivero, C Galés, J-M Senard, I A Lüthy, C Davio*, A Bruzzone*. Oncotarget 5(20):10058-69. 2014. ISSN 1949-2553 FI2013 6.359. # and * contributed equally to this study.
  51. Multidrug resistance protein 4/ ATP binding cassette transporter 4: a new potential therapeutic target for acute myeloid leukemia. Sabrina Copsel, Ariana Bruzzone, Maria May, Julien Beyrath, Victoria Wargo, Jeannette Cany, Frans G.M. Russel, Carina Shayo, Carlos Davio. Oncotarget 5(19):9308-21. 2014. ISSN 1949-2553 FI2014 6.359.
  52. G protein-coupled receptor30–adenylyl cyclase–protein kinase A pathway is involved in estradiol 17ß-D-glucuronide-induced cholestasis. Andrés E. Zucchetti, Ismael R. Barosso, Andrea C. Boaglio, Cecilia L. Basiglio, Diego R. Taborda, Marcelo G. Luquita, Carlos A. Davio, Marcelo G. Roma, Fernando A. Crocenzi, Enrique J. Sánchez Pozzi. Hepatology. 59:1016-1029. 2014. ISSN 0270-9139 FI2014 11.056.
  53. Signal transduction mechanism of biased ligands at histamine H2 receptors. Alonso N, Monczor F, Echeverría E, Davio C, Shayo C, Fernandez N. Biochem J. 459 (1):117-126. 2014. ISSN 0264-6021 FI2012 4.654
  54. Cyclic AMP efflux through MRPs is critical in the regulation of bovine sperm capacitation: contribution of A1 adenosine receptors. Claudia Osycka Salut#, Federico Diez#, Burdet Juliana, Maria Gracia Gervasi, Ana Franchi, Liliana G Bianciotti, Carlos Davio* and Silvina Perez-Martinez*. (#) Claudia Osycka Salut and Federico Diez contributed equally to this study. (*)Corresponding authors. Mol Hum Reproduction. 20(1):89-99. 2014. ISSN 1360-9947 FI2012542. Editor's highlight. Professor Christopher Barratt, Editor-in-Chief.
  55. Antihistaminergics and inverse agonism. Potential therapeutic applications. Federico Monczor, Natalia Fernandez, Carlos P. Fitzsimons, Carina Shayo, Carlos Davio. Eur J Pharmacol. 715:26-32. 2013. ISSN 0014-2999 FI2011516.
  56. Pharmacodynamic study of the 7,8-dihydroxy-4-methylcoumarin-induced selective cytotoxicity towards U-937 leukemic cells versus mature monocytes: cytoplasmic p21Cip1/WAF1 as resistance factor. Vázquez R,Riveiro ME, Mondillo C, Perazzo JC, Vermeulen M, Baldi A, Davio C*, Shayo C*. Biochem Pharmacol, 86(2):210-21, 2013.  ISSN 0006-2952 FI201258. *These authors contributed equally to the direction of the study.
  57. On the role of ATP release, ectoATPase activity and extracellular ADP in the regulatory volume decrease of Huh-7 human hepatoma cells. Espelt MV, de Tezanos Pinto F, Alvarez CL, Sanchez Alberti G, Incicco J, Leal Denis MF,Davio C, Schwarzbaum PJ. Am J Physiol Cell Physiol.  304(10):1013-1026. ISSN 0363-6143 FI2011 3.54.
  58. Cross-desensitization and cointernalization of H1 and H2 histamine receptors reveal new insights into histamine signal integration. Alonso N, Fernandez N, Notcovich C, Monczor F, Simaan M, Baldi A, Gutkind JS,Davio C, Shayo C. Mol Pharmacol. 83(5):1087-98. ISSN 0026-895X   FI2012  4.41
  59. Semen promotes the differentiation of tolerogenic dendritic cells. RemesLenicov, F., Rodriguez Rodrigues, C., Sabatté, J, Cabrini, M., Jancic, C., Ostrowski, M., Merloti, A., Gonzalez, H., Donaldson, M., Pasqualini, R.S., Davio, C., Geffner, J., Ceballos, A. J Immunol. 189(10):4777-86. ISSN 0022-1767 FI2011 5.788
  60. Structure-anti-leukemic activity relationship study of ortho-dihydroxycoumarins in U-937 cells: key role of the δ-lactone ring in determining differentiation-inducing potency and selective pro-apoptotic action. Ramiro Vázquez, María E. Riveiro, Mónica Vermeulen, Eliana Alonso, Carolina Mondillo, Natalia Gómez, Graciela Facorro, Lidia Piehl, Albertina Moglioni, Natalia Fernández, Alberto Baldi, Carina Shayo, Carlos Davio. Bioorg Med Chem. 20(18):5537-49. 2 ISSN 0968-0896 FI2011 2.921
  61. Iron and holotransferrin induce cAMP-dependent differentiation of Schwann cells. Carolina Salis; Carlos Davio; Vanina Usach; Nicolas Urtasun; Belen Goitia; Rocio, Martinez Vivot; Juana M Pasquini; Patricia Setton-Avruj.  Neurochemistry International 61(5):798-806. ISSN 0197-0186 IF2011 2.857
  62. Toddaculin, a natural coumarin from Toddalia asiatica, induces differentiation and apoptosis through different signaling pathways in U-937 leukemic cells. Ramiro Vázquez, María E. Riveiro, Mónica Vermeulen, Carolina Mondillo, Philip H. Coombes, Neal Crouch, Fathima Ismail, Dulcie A. Mulholland, Alberto Baldi, Carina Shayo, Carlos Davio. Phytomedicine. 19(8-9):737-46. 2012. ISSN 0944-7113 IF2011268
  63. ALAS-1 gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FOXO1 by vanadate in diabetic mice. Oliveri LM,Davio C, Batlle AM, Gerez EN. Biochem J. 442(2):303-10, ISSN 0264-6021 FI2011 4.897
  64. Roles of phosphorylation dependent and independent mechanisms in the regulation of Histamine H2 receptor by G Protein-coupled Receptor Kinase. Fernandez N, Gottardo F, Alonso N, Monczor F, Shayo C, Davio C. J Biol Chem. 286(33):28697-706, 2011. ISSN 0021-9258 FI2011 773
  65. Synthesis, structural characterization and proapoptotic activity of 1-indanone thiosemicarbazones platinum (II) and palladium (II) complexes: Potential role as selective antileukemic agents. Natalia Gómez, Diego Santos, Ramiro Vázquez, Leopoldo Suescun, Álvaro Mombrú, Monica Vermeulen, Liliana Finkielsztein, Carina Shayo, Albertina Moglioni, Dinorah Gambino, Carlos Davio. ChemMedChem, 6(8):1485-94, 2011. ISSN 1860-7179 FI2011151
  66. Atrial natriuretic factor stimulates cAMP efflux in the rat exocrine pancreas through Multidrug Resistance Associated Proteins. Rodriguez M#, Diez F#; Ventimiglia MS, Morales VP, Copsel S, Vatta MS, Davio C*, Bianciotti, LG*. 140(4): 1292-1302, 2011. ISSN 0016-5085 FI2011 11.675. # and * contributed equally to this study.
  67. Multidrug Resistance Protein 4 (MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cell proliferation and differentiation. Copsel S, Garcia C, Diez F, VermeulemM, BaldiA, BianciottiLG, RusselFGM, Shayo Cand Davio C. J Biol Chem. 286(9): 6979–6988, 2011. ISSN 0021-9258 FI2011 773
  68. Endothelins participate in the central and peripheral regulation of submandibular gland secretion in the rat. Maria Ventimiglia, Myrian Rodriguez, Vanina Morales, Juan Elverdin, Juan Perazzo, Mauricio Castañeda, Carlos Davio, Marcelo Vatta, and Liliana Bianciotti. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology. 300(1):R109-20. 2011. ISSN 0363-6119 FI2011 336
  69. The expression of a g protein coupled receptor (GPCR) leads to the attenuation of other GPCRs signaling. Experimental evidence for a spontaneous GPCR constitutive inactive form. Tubio MR, Fernandez NC, Fitzsimons CP, Copsel S, Santiago SD, Shayo CC, Davio CA, Monczor F. J Biol Chem. 285(20):14990-8. ISSN 0021-9258 FI2010 5.328
  70. Histamine acting on H1 receptor promotes inhibition of proliferation via PLC, RAC, and JNK-dependent pathways. Notcovich C, Diez F, Tubio MR, Baldi A, Kazanietz MG, Davio C, Shayo Exp Cell Res. 316:4011–41. 2010 ISSN 0014-4827 FI2010 3.609.
  71. Coumarins: Old compounds with novel promising therapeutic perspectives, ME. Riveiro, N. De Kimpe, A. Moglioni, R. Vázquez, F. Monczor, C. Shayo, Davio. Curr Med Chem 17(13):1325-1338. 2010. ISSN 0929-8673 FI2010 4.63.

Publicaciones previas relevantes

  1. Mepyramine, a histamine H1 receptor inverse agonist, binds preferentially to a G protein-coupled form of the receptor and sequesters G protein. Fitzsimons CP, Monczor F, Fernandez N, Shayo C, Davio C. J Biol Chem.279(33):34431-9.  ISSN 0021-9258 FI 2004 6.355.
  2. Tiotidine, a histamine H2 receptor inverse agonist that binds with high affinity to an inactive G-protein-coupled form of the receptor. Experimental support for the cubic ternary complex model. Monczor F, Fernandez N, Legnazzi BL, Riveiro ME, Baldi A, Shayo C, Davio C. Mol Pharmacol. 64(2):512-520. 2003. ISSN 0026-895X FI200365.
  3. Reduction of G protein-coupled receptor kinase 2 expression in U-937 cells attenuates H2 histamine receptor desensitization and induces cell maturation. Fernandez N, Monczor F, Lemos B, Notcovich C, Baldi A, Davio C, Shayo C. Mol Pharmacol. 62(6):1506-1514. 2002. ISSN 0026-895X FI200248
  4. Histamine H2 receptor desensitization: involvement of a select array of G protein-coupled receptor kinases. Shayo C, Fernandez N, Legnazzi BL, Monczor F, Mladovan A, Baldi A, Davio C. Mol Pharmacol. 60(5):1049-1056. 2001. ISSN 0026-895X FI200145.

Capitulos de libros internacionales con referato (últimos años)

  1. Histamine H2 Receptor in Blood Cells: A Suitable Target for the Treatment of Acute Myeloid Leukemia. Federico Monczor, Sabrina Copsel, Natalia Fernandez, Carlos Davio, and Carina Shayo. Handbook of Experimental Pharmacology, Springer International Publishing Switzerland. 2017. 241:141-160. doi: 10.1007/164_2016_8
  2. Histamine H2 Receptor Biased Signaling Methods. Natalia Fernández, Shayo Carina, Davio Carlos, Monczor Federico. Pag. 67-114. (517 totales). Methods in Pharmacology and Toxicology. Histamine Receptors as Drug Targets. Editores Tiligada, Ekaterini and Ennis, Madeleine. ISBN 978-1-4939-6843-5. Springer International Publishing AG.

 

FINANCIMIENTO

Subsidios de apoyo a proyectos de investigación en ejecución

  • Universidad de Buenos Aires - UBACYT- 20020220200128BA (2023-) - “REPOSICIONAMIENTO RACIONAL DE FÁRMACOS PARA COMPLEMENTAR LA TERAPÉUTICA DEL CÁNCER DE PÁNCREAS. LOS ANTI-INFLAMATORIOS NO ESTEROIDEOS COMO FAMILIA SELECCIONADA”. Monto asignado $ 320000. Director: Dr. Carlos Davio
  • Agencia de Promoción Científica y Tecnológica - PICT-2022-0214 (2024-2028) - PARTICIPACIÓN DEL TRANSPORTADOR ASOCIADO A LA RESISTENCIA MÚLTIPLE A DROGAS (MRP) MRP4/ABCC4 EN EL CROSS-TALK PARÉNQUIMA-ESTROMA DE ADENOCARCINOMAS DUCTALES PANCREÁTICOS (PDAC). Director: Dr. Carlos Davio - Grupo responsable: Dra. Ana Sahores y Dra. Natalia Gomez

Subsidios de apoyo a proyectos de investigación ejecutados recientemente:

  1. Agencia de Promoción Científica y Tecnológica - PICT-2018-4462 (2020-2023) - MRP4/ABCC4 EN ADENOCARCINOMA DUCTALES PANCREÁTICOS (PDAC): ESTUDIO DE LOS MECANISMOS QUE CONDUCEN A LA DESREGULACIÓN DE SU EXPRESIÓN E IMPLICANCIAS TERAPÉUTICAS. Monto asignado $ 1.440.000. Director: Dr. Carlos Davio - Grupo responsable: Dr. Agustín Yaneff y Dra. Betina González.
  2. Universidad de Buenos Aires - UBACYT-20020170100674BA (2018-2021) - “MRP4/ABCC4, como nuevo blanco terapeutico en Adenocarcinoma ductal pancreatico”. Director: Dr. Carlos Davio - Responsable de grupo: Dr. Agustín Yaneff y Dra. Carolina Ghanem.
  3. PUE-0045- CONICET - 2017 - "Aproximacion interdisciplinaria para el desarrollo y la optimizacion de aplicaciones farmacologicas en terapias dirigidas a cancer de pancreas y vesicula y rutas biliares: validacion de blancos terapeuticos, diseño y optimizacion racional de drogas". Investigador principal: Dr. Carlos Davio.