TCFL5, initially cloned by us as CHA, is a member of the bHLH transcription factor family. We found that human TCFL5 gene locus is a complex with 4 isoforms. Besides, we performed interactome analysis of all TCFL5 isoforms. The 2 major isoforms, TCFL5 and CHA, will result from alternative promoter usage and differential transcription, rather than from gene splicing. We have confirmed binding to those promoters of Notch1, Egr1 and c-Myc. We found that CHA isoform, but not TCFL5 can bind to c-Myc and repressed its transcriptional activity in several cancer cell lines. Notch1 can bind to TCFL5 promoter and induce TCFL5 isoform. On the contrary, c-Myc can induce both TCFL5 and CHA transcription. We have also defined a set of genes regulated by TCFL5/CHA in leukemia cell lines and established its role in the prognosis and development of B-and T-acute lymphoblastic leukemia and in normal hematopoiesis.

The protozoan parasite, Trypanosoma cruzi causes Chagas’ disease. We addressed the impact of T. cruzi genetic variability in the clinical outcome and immunopathology of the disease. We addressed the role that T cell CD4+ subsets, myeloid subclasses including myeloid-derived suppressor cells (MDSC) have in the immunopathogenesis with special focus on myocarditis, both in animal models and in patients, which differ depending of the infecting strain. To address this enormous complexity we used a system biology multiomic approaches including genomics, transcriptomic, metabolomics, etc. We have found many metabolic, miRNA and mRNA transcription alterations in T. cruzi infection suggesting a stressful condition in the heart. Serum miRNAS are excellent Biomarkers of Chagas’ disease progression. Besides, we defined Slamf1 as a new T. cruzi receptor.