• Molecular Genetics: genetic causes of cardiac arrhythmias
• Molecular Biology: new genes and mutations involved in
  cardiac arrhythmias
• Molecular Physiology: New molecular pathways involved
  in cardiac diseases.
• Biomarker in neuroscience and cardiovascular disease.
• Drug molecular targets

The Molecular Genetics Program at the MMRL is currently one of a handful of medical research centers worldwide capable of studying the genetic causes of the lethal cardiac arrhythmias responsible for sudden cardiac death in infants, children and young adults and designing gene-specific therapy to help treat them. We start with the selection of physiologically and genetically meaningful markers in cardiac diseases and population stratification. The aim of the program is to understand the role that different cardiac ion channels and regulatory proteins play in the normal functions of the human heart and/or cause diseases. As result of the collaboration with Hospitals and Universities, we are provided blood from patients suffering acquired and congenital Long QT, Short QT, Brugada Syndrome, Sudden Infant Death Syndrome (SIDS) and atrial fibrillation. Following extraction of the DNA, direct PCR-sequencing is performed to identify variations in the coding sequence. The potential mutant gene is then study by cloning and expression in a human cell line so as to identify the nature of the cellular defect. The characteristics of the defect provide us specific direction for the design of novel drugs and other innovative approaches to therapy. Thus, starting and ending with patients in the clinic, we are able to bring the research full circle by delving into the cause of disease at the genetic level.

Accomplishments: We have identified two new genes associated with sudden cardiac death and one associated with atrial fibrillation. These genes are potential diagnostic and therapeutic targets for both the hereditary and the acquired forms of cardiac diseases. As part of this work, we have showed that in the Irx5-deficient mice, the cardiac depolarization gradient is abolished and increased susceptibility to arrhythmias (Cell, Vol. 123, 347-358, October 21, 2005).

PCR-sequence, genotyping, quantitative real-time PCR, Microarray technology, protein purification and analysis. RNAi, gene cloning and mutagenesis of ion channels for expression and electrophysiological studies. Primary and cell line culture, transfection. Adenovirus technology for gene therapy.

Guido D. Pollevick, Javier M. Di Noia, Laura Salto, Carlos Lima, M. Susana Leguizamón, Rosa de Lederkremer and Alberto C.C. Frasch. Trypanosoma cruzi surface mucins with exposed variant epitopes. J. Biol. Chem. (2000) vol. 275, 27671-27680 PubMed ID: 10843987

Marcela Brocco, Guido D. Pollevick and Alberto C.C. Frasch. Differential regulation of polysialyltransferase expression during hippocampus development: Implications for neuronal survival. J Neurosci Res. (2003) vol. 74, 744-753 PubMed ID: 14635225

Ramon Brugada, Kui Hong, Robert Dumaine, Jonathan Cordeiro;Fiorenzo Gaita; Martin Borggrefe; Teresa M. Menendez; Josep Brugada; Guido D. Pollevick; Christian Wolpert; Elena Burashnikov, Kiyotaka Matsuo; Yue Sheng Wu; Alejandra Guerchicoff; Francesca Bianchi, Carla Giustetto; Rainer Schimpf; Pedro Brugada; Charles Antzelevitch. Sudden Death Associated With Short-QT Syndrome Linked to Mutations in HERG. Circulation. (2004) vol. 109, 30-35. PubMed ID: 14676148

Julieta Alfonso, Guido D. Pollevick, Marieke G. van der Hart, Gabriele Flügge, Eberhard Fuchs and Alberto C.C. Frasch. Identification of genes regulated by chronic psychosocial stress and antidepressant treatment in the hippocampus. Eur J Neurosci. (2004) vol. 19, 659-666. PubMed ID: 14984416

Kui Hong, Josep Brugada, Antonio Oliva, Antonio Berruezo-Sanchez, Domenico Potenza, Guido D Pollevick, Alejandra Guerchicoff, Kiyotaka Matsuo MD, Elena Burashnikov, Robert Dumaine, Jeffrey A Towbin, Vladislav Nesterenko, Pedro Brugada, Charles Antzelevitch, Ramon Brugada. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation. (2004) vol. 110, 3023-3027. PubMed ID: 15520322

Julieta Alfonso, Fernan Aguero, Daniel O. Sanchez, Gabriele Flügge, Eberhard Fuchs, Alberto C.C. Frasch and Guido D. Pollevick. Gene Expression Analysis in the Hippocampal Formation of Tree Shrews Chronically Treated with Cortisol. J Neurosci Res. (2004) vol. 78, 702-710. PubMed ID: 15505804

Kui Hong†, Alejandra Guerchicoff†, Guido D. Pollevick†, Antonio Oliva, Robert Dumaine, Mark de Zutter, Elena Burashnikov, Yue Sheng Wu, Josep Brugada, Pedro Brugada and Ramon Brugada. Cryptic 5' Splice-site Activation in SCN5A Associated with Brugada Syndrome. †These authors contributed equally to this work. J Mol Cell Cardiol. (2005) vol. 38, 555-560. PubMed ID: 15808832

Danny L. Costantini, Eric P. Arruda, Pooja Agarwal, Kyoung-Han Kim, Yonghong Zhu, Wei Zhu, Melanie Lebel, Chi Wa Cheng, Chong Y. Park, Stephanie A. Pierce, Alejandra Guerchicoff, Guido D Pollevick, Toby Y. Chan, M. Golam Kabir, Shuk Han Cheng, Mansoor Husain, Charles Antzelevitch, Deepak Srivastava, Gil J. Gross, Chi-chung Hui, Peter H. Backx and Benoit G. Bruneau. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell (2005) vol.123, 347-358.

Sami Viskin, Raphael Rosso, Ori Rogowski, Bernard Belhassen, Aviva Levitas, Abraham Wagshal, Amos Katz, Dana Fourey, David Zeltser, Antonio Oliva, Guido D. Pollevick, Charles Antzelevitch, and Uri Rozovski. Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome Eur Heart J. (2006) vol.27, 469-475

Fabiana S. Scornik, Mayurika Desai, Ramon Brugada, Alejandra Guerchicoff, Guido D. Pollevick, Charles Antzelevitch and Guillermo J. Perez. Functional expression of the "cardiac type" Nav1.5 sodium channel in canine intracardiac ganglia. Heart Rhythm, in press 2006