The Signal Transduction and Drug Design Laboratory is oriented to the comprehension of those molecular mechanisms involved in the transmission of the biological information from extracellular to intracellular media in order to evoke a biologic response. The utter understanding of the regulatory mechanism underneath transduction process allows the identification of fundamental bases for rational drug design of pharmacologic tools with potential therapeutic applications, and also the elucidation of the mechanisms of action of commercially available drugs.

Under these objectives and in collaboration with other groups, we carry out an interdisciplinary research involving in silico, in vitro and in vivo approaches to face the current drug design challenge.



Investigadora Independiente CONICET, Profesora Adjunta Química Medicinal-FFyB-UBA.


Becaria post-doctoral CONICET, Ayudante de segunda Química Biológica.


Becaria post-doctoral CONICET, Ayudante de primera Química Biológica.


Becaria INC, Estudiante de Bioquímica.



GRK2 is involved in many diseases where GPCRs response regulation is altered. The main objective of this line relies on the identification and evaluation of compounds with inhibitory effect over RGS (Regulator of G protein Signalling) activity of GRK2. Hence, we consider GRK2 as a multidomain and multifunctional protein, with a desensitizing role beyond its kinase activity, and also involving multiple RGS effects.. In first instance, these studies will allow the validation of RGS activity of GRK2 as drug target, and secondly, the identification of potential inhibitors and the discovery of pharmacological prototypes for a future drug development.


Recently, it has been described that beyond second messenger modulation, many GPCRs can signal in a G-protein independent manner. Since historically the efficacy of histaminergic ligands was defined according to second messenger response, this findings gave rise to enquiries about actual ligands classification. The main objective of this research is to evaluate the faculty of histaminergic ligands (classically known as antagonists or inverse agonists) to promote desensitization and internalization of receptors, and to evoke other responses with G proteins not being involved. Identification y characterization of these events will allow the avoidance of undesired but specific effects.


The control of cardiac function mainly depends on B-adrenergic receptors function. B3-adrenergic receptor (B3AR) contributes to myocardium function regulation, antagonizing B1 and B2 adrenergic receptors effect, hence protecting the heart from the damage induced by a sustained adrenergic stimulation. Since the lack of consensus phosphorylation sites on its structure, B3AR is resistant to desensitization mediated by kinase activity of PKA and GRKs. Therefore, the main objective of this research is to elucidate the underlying mechanisms of the regulation of B3AR signalling and expression, and its relevance in B3AR cardioprotective effect.


  1. PI3K pathway is involved in ERK signaling cascade activation by histamine H2R agonist in HEK293T cells.N Alonso, A Diaz-Nebrada, F Monczor, JS Gutkind, C Davio, N Fernandez y C Shayo. Biophys Acta. 2016; 1860(9):1998-2007.
  2. Physiological implications of biased signaling at histamine H2 receptors.N Alonso, CD Zappia, M Cabrera, C Davio, C Shayo, F Monczor, N Fernández. Front Pharmacol. 2015. 6:45. doi:10.3389/fphar.2015.00045.
  3. G2/M cell cycle arrest and tumor selective apoptosis of malignant hematopoietic 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):e0136878. Doi:10.1371/journal.pone.0136878.
  4. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways. CD Zappia, G Granja-Galeano, N Fernández, C Shayo, C Davio, CP Fitzsimons y F Monczor. Sci Rep. 2015; 5:17476
  5. Dual role of cAMP in the transcriptional regulation of multidrug resistance-associated protein 4 (MRP4) in pancreatic adenocarcinoma cell lines.A Carozzo, F Diez, N Gomez, M Cabrera, C Shayo, C Davio, N Fernández. PLoS ONE. 2015. 10(3): e0120651. doi:10.1371/journal.pone.0120651.
  6. Signal transduction mechanism of biased ligands at histamine H2 receptors.Alonso N, Monczor F, Echeverria E, Davio C, Shayo C, Fernández N. Biochem J. 2014. 459(1):117-26.
  7. Antihistaminergics and inverse agonism. Potential therapeutic applications.Monczor F, Fernandez N, Fitzsimons CP, Shayo C, Davio C. Eur J Pharmacol.  (1-3)715:26-32.
  8. Oligodendrocyte Differentiation and Signaling After Transferrin Internalization: A Mechanism of Action.Pérez MJ, Fernandez N, Pasquini JM. Exp Neurol. 2013 248C:262-274.
  9. 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. May;83(5):1087-98. 2013.
  10. Roles of phosphorylation dependent and independent mechanisms in the regulation of Histamine H2 receptor by G Protein-coupled Receptor Kinase 2.Fernandez N, Gottardo F, Alonso N, Monczor F, Shayo C, and Davio C. J Biol Chem. 286(33):28697-706. 2011.
  11. 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. 285:14990-8. 2010.

Book Chapters:

HISTAMINE H2 RECEPTOR BIASED SIGNALLING METHODS para el volumen de Methods in Histamine Receptors de la colección SPRINGER PROTOCOLS. N Fernandez, C Shayo, C Davio, F Monczor. (Idioma: Inglés)

HISTAMINE H2 RECEPTOR IN BLOOD CELLS: A SUITABLE TARGET FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA del libro Handbook of Experimental Pharmacology. Editorial: Berlín, New York, Springer-Verlag, Alemania. ISSN 0171-2004. F Monczor, S Copsel, N Fernandez, C Davio, C Shayo. (Idioma: Inglés). Junio 2016.

EVALUACIÓN DE UN SISTEMA HORMONA-RECEPTOR del libro Fisiopatología Molecular y Clínica Endcorinológica. F Monczor, N Fernandez, JC Calvo. ISBN 978-987-45792-0-1. Neuhaus Industria Gráfica. Buenos Aires, Argentina 2015. RS Calandra, MB Barontini (Editores), MA Pisarev, GJ Juvenal, R Rey (Editores Asociados).


Subsidio para grupos en formación, Agencia de Promoción Científica y Tecnológica –SECYT, PICT 2015-2443. Identificación, obtención y evaluación de inhibidores de la actividad RGS de GRK2. IR. Dra. Natalia Fernández

Subsidio de la Universidad de Buenos Aires-UBACYT-20020130100624BA (2014-2017) – “Exclusión de AMPc y MRP4/ABCC4 como determinantes del balance AMPc-intracelular vs AMPc extracelular. Implicancias en la progreión celular maligna”. IR: Dr. Carlos Davio

Subsidio de la Agencia de Promoción Científica y Tecnológica. PICT-E-2014-0219 para la adquisición de equipamiento. IR: Dr. Carlos Davio.

Subsidio de la Agencia de Promoción Científica y Tecnológica, PICT-2013-2050 (2014-2017) “Exclusión de AMPc y MRP4/ABCC4 como determinantes del balance AMPc-intracelular vs AMPc extracelular. Implicancias en la progresión celular maligna”. Dr. Carlos Davio.

Subsidio del CONICET, PIP-112-201201-00562. 2013-2015. “Mecanimos de la regulación cruzada entre los receptores H1 y H2 a histamina”. IR: Dra. Carina Shayo.



Dr. Pablo Lorenzano-Menna – Investigador Adjunto CONICET de la Universidad Nacional de Quilmes.

Dra. Carina Shayo – Investigadora Independiente del CONICET del Instituto de Biología y Medicina Experimental (IBYME-CONICET).

Dr. Fernando Dominici – Investigador Independiente, CONICET, IQUIFIB-CONICET.

Dra. Andrea Randi – Investigadora Independiente, CONICET, Dpto de Bioquímica Humana, Facultad de Medicina, UBA.

Dr. Federico Remes Lenicov – Investigador Aistente CONICET, INBIRS-UBA-CONICET.