Postdoctoral Fellow

Ricardo Martins-Ferreira

Profile

Ricardo Martins-Ferreira is a postdoc at the Epigenetics and Immune Disease Group studying of Inborn Errors of Immunity and B-cell acute lymphoblastic leukaemia associated with IKZF1 mutations. His background includes Bachelor’s and Master’s in Biochemistry, and a PhD in Biomedical Sciences from the University of Porto in Portugal. His research has focused on the epigenetic events involved in neurodegenerative diseases, exploring the role of microglia in neuroinflammation.

Project description

IKZF1 encodes the transcription factor IKAROS, which is pivotal in lymphocyte differentiation and development. Mutations in IKZF1 are associated with both primary immunodeficiencies (PIDs) and lymphocyte malignancies, particularly B-cell acute lymphoblastic leukemia (B-ALL). IKAROS forms homo or heterodimers and interacts with DNA and epigenetic enzymes through different domains. The receiving team (Dr. Ballestar’s lab) is expert in epigenetic regulation in primary immunodeficiencies, particularly common variable immunodeficiency (CVID), a B cell deficiency for which 80% of cases have no associated mutations, but the remaining are characterized by monogenic mutations, including in IKZF1. Dr. Ballestar’s team reported drastic changes in DNA methylation and expression in memory B cells in CVID patients without mutations. One of the interests of this lab is to dissect the contribution of genes mutated in CVID to epigenetic dysregulation and to identify common pathogenic manifestations in CVID patients exhibiting similar clinical manifestations. Depicting the role of IKAROS in a monogenic pathology can help extrapolate how those can be implicated in more genetically complex pathologies, like B-ALL, particularly considering the association of IKZF1 mutations with worst prognosis and relapse. In this project, I intend to address these questions through the following goals: 1) Obtain the epigenomic and transcriptomic profiles of B cells from monogenic IKZF1 CVID comparing them to CVID patients without mutations to identify shared dysregulated targets, and dissecting the specific contribution of IKAROS; 2) Infer the contribution of IKAROS targets to B cell dysfunction in B-ALL associated with disease relapse; 3) Generating B cell-based models associated with different IKAROS mutations to recapitulate dysregulation events. This program will involve key international and intersectional secondments with Dr. Sergio Rosenzweig at NIH (expert in IKAROS mutations and PIDs), Dr. Raffaella di Micco at Ospedale San Raffaele (expert in gene editing), and Dr Jairo Rodriguez at qGenomics (expert in bioinformatics).