Joaquín Arribas, PhD

2009-2010 BCRF Project:
Overexpression of HER2, a member of the HER family of tyrosine kinase receptors, is observed in 15% to 30% of human breast cancers, and is predictive of poor outcome. The first step in HER receptor activation is the dimerization and the autophosphorylation of several residues in the cytoplasmic domain. Several well-characterized signal transducers are recruited to the plasma membrane through these phospohrylated residues, particularly phosphotyrosines. Although this process has been studied already, and almost a dozen partners have been characterized in detail, recent proteomic studies have shown the existence of many unknown HER receptor-binding partners. Therefore, one of the aims of this proposal is identifying and characterizing novel partners of HER2 contributing to the oncogenic activity of this receptor.

In contrast with the phosphotyrosines, very little is known about the functionality of phosphoserine/threonine residues of HER2. Since the few HER1 phosphoserine/threonine residues studied that have been studied are functionally relevant, it seem that the identification and characterization of phosphoserine/threonine residues in the cytoplasmic tail of HER2 is worthwhile. Thus, Dr. Arribas also proposes a series of experiments to accomplish this goal and determine the role of these phosphoserine/threonines in breast cancer progression.

Mid-Year Progress Report:
During the past six months, Dr. Arribas and his lab have already carried out the proteomic approach to look for novel factors that bind activated HER2. As a result, they have identified nearly a dozen protein candidates whose binding depends on the activity of HER2. In addition they have already constructed several cell lines expressing mutants lacking serine residues that are phospho- or dephosphorylated upon HER2 dimerization. In the next six months they will validate and characterize the novel HER2-binding partners as well as functionally characterize the cell lines expressing HER2 with mutations in serine/threonine that they have generated.

Bio:
Joaquín Arribas is the Director of the Medical Oncology Research Program at Vall d'Hebron University Hospital Research Institute, Barcelona, Spain, where he leads a group focussed on the study of growth factors, growth factor receptors as well as the proteases involved in remodeling the cell surface. He is a member of the Editorial Board of the Journal of Biological Chemistry. Translational Oncology and CDB Protein Systems.

Dr. Arribas is member of the Spanish and American Societies of Biochemistry and Molecular Biology and President of the Committee for the Evaluation of research project on Cancer of the "Carlos III" health institute, the major public funding agency in Spain.

Dr. Arribas completed his undergraduate studies in biochemistry at the Autonomous University of Madrid in 1987. At the same university, he subsequently worked on the regulation of the catalytic activities of the proteasome and received a Ph. D. in biology in 1991. Sponsored by a fellowship from the Spanish Ministry of Education and Science, he joined the Memorial Sloan-Kettering Cancer Center (New York, USA) as a postdoctoral fellow to work with Dr. Joan Massagué (1992-1996) on the proteolytic processing of transmembrane growth factors. In 1997, he joined the oncology department at Hospital Vall d'Hebron in Barcelona as a staff scientist and was promoted to lead the oncology research department in 2001. His research has been recognized by an EMBO Young Investigator Programme (YIP) award and the Beckman Coulter award to the Best Young Spanish Investigator in Biochemistry and Molecular Biology.