Desenvolupament i malalties limfocítiques

  • Parra Group Aug 2019
ICO - German Trias i Pujol

(+34) 93 557 2800 extn 4210

Josep Carreras Leukaemia Research Institute
Can Ruti Campus
Ctra de Can Ruti, Camí de les Escoles s/n
08916 Badalona, Barcelona
Spain

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Summary

Proper generation of B lymphocytes is fundamental for creating a humoral immune response against external and internal pathogens. B cell lymphopoiesis is a complex developmental process that implies several cellular transitions including cell commitment and early and late cellular differentiation. At each differentiation step, cells undergo extensive genetic and epigenetic reprogramming to acquire the specific gene signature characteristic of the new cellular entity generated. How specific gene expression programs are selected and maintained, resulting in the proper generation of B cells, remains a fundamental question in biology. Conversely, how the aberrant establishment of cell- and lineage-specific gene transcriptional programs leads to the development of B cell malignancies such as leukemia, lymphoma, immunodeficiencies and autoimmunity also needs extensive investigation.

Research

Our group is devoted to understanding the transcriptional and epigenetics events underlying B cell development and their potential deregulation in leukemia and lymphoma. We work on the concept that gene transcriptional repression is critical for the acquisition of proper B cell identity.

The main research lines of our laboratory are:

1. Investigating the role of the transcriptional repressor HDAC7 during B cell development

Using mouse models our laboratory has demonstrated that the histone deacetylase HDAC7 is a master transcriptional repressor during early B cell development in the bone marrow. Going beyond our current knowledge, we are currently studying its potential contribution during terminal B cell differentiation, in particular during the germinal center reaction.

2. Identifying novel epigenetic regulators essential for proper B cell generation

Based on our current knowledge we plan to define the role of additional epigenetic regulators in normal and aberrant B cell generation.

3. Establishing HDAC7 as a novel biomarker and potential therapeutic target in pro-B acute lymphoblastic leukemia (pro-B-ALL) and Diffuse Large B Cell Lymphoma (DLBCL)

We have observed that HDAC7 is under-expressed in infant and adult pro-B-ALL patients as well as in DLBCL cell lines. We aim to identify of the mechanism(s) responsible for the loss of HDAC7 expression with the main goal of uncovering novel small molecules for combinatorial and precision therapy.

4. Implementing 3D organoid cultures from DLBCL sample patients.

The implementation of 3D organoid models for testing patient responses will represent a “game-change” in the field: proof-of-concept and innovative tool to perform compound library screenings to unveil new drugs to be used in combinatorial therapy with current treatments in a personalized manner.

 

Collaborations

Dr Parra has several collaborative projects underway with national and international groups.

Dr Pablo Menéndez, Instituto de Investigación contra la leukemia Josep Carreras, Barcelona

Dr Thomas Graf, Centre de Regulació Genòmica (CRG), Barcelona

Dr Almudena Ramiro, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Barcelona

Dr Sergio Roa, Centro de Investigación Médica Aplicadoa, Pamplona

Dr Biola Javierre, Instituto de Investigación contra la leukemia Josep Carreras, Badalona

Dr Mireia Camós, Hospital Sant Joan de Deu, Barcelona

Dr Tokameh Mahmoudi, Erasmus Medical Center, Rotterdam

Dr Pantelis Hatzis, BSCR Alexander Fleming, Vari, Greece

People