Joaquin Arribas, PhD

2007-2008 BCRF Project:
A subgroup of HER2 positive breast cancers express truncated forms of the HER2 receptor known as carboxy terminal fragments of HER2 (HER2 CTFs). Patients with HER2 CTFs-expressing tumors have worse outcome and are more likely to develop metastasis. Although different lines of evidence indicate that HER2 CTFs play a causal role in tumor invasion, the mechanisms and factors involved are unknown and there are no laboratory models to tackle this question. In this project, Dr. Arribas proposes different approaches to address the function of individual HER2 CTFs as well as the development of laboratory models. In addition, he and his team will perform a screening to analyze the expression of individual HER2 CTFs in breast cancer samples and will look for possible clinical correlations. Finally, the investigators will determine the effectiveness of anti-HER2 therapies both in laboratory models expressing different HER2 CTFs and in patients expressing the most active ones. The objective of these studies is to determine which CTFs are involved in the development of metastasis and the mechanisms involved.

Mid-Year Progress Report:
During the last six months Dr. Arribas and his team have characterized four breast cancer cell lines engineered to express individual CTFs, and they are continuing their effort and their transcriptomic analysis to identify the genes specifically regulated by 611-CTF. Collectively, their results indicate that this CTF contributes to tumor progression and invasion and is likely responsible for the poor prognosis of HER2 CTF positive breast cancer patients.

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.