© copyright DIAZ-MUNOZ Manuel D. (2019)

Manuel Diaz-MunozCentre de physiopathologie Toulouse Purpan (CPTP) - CNRS / Inserm / Université Toulouse 3

Working for better understanding of the molecular mechanisms controlling B cell-mediated immune responses

Mes recherches

My research is focused to understand which are the key molecular players that regulate immune responses. During my PhD in Madrid I studied how macrophages regulate acute pro-inflammatory responses against pathogens and chronic inflammation in the context of cardiovascular diseases. Later I grew a profound interest on understanding further the molecular signatures that configurate our highly efficient immune system. During my stay as PostDoc in Cambridge, UK I uncovered the important roles of the RNA binding proteins HuR and Tia1 in mediating antibody and memory immune responses. My research as ATIP-Avenir group leader (2018) and Inserm CRCN (2019-2020) at the Centre for Physiopathology Toulouse Purpan relates to my interest on understanding how RBPs regulate the life and function of messenger and non-coding RNA molecules during B cell development, differentiation and tumour transformation. In this regard, we now integrate functional in-vivo analysis of the immune response upon infection with next generation sequencing and bioinformatics to uncover the functions of RNA binding proteins as modulators of the DNA damage response and apoptosis, two mechanisms that are universally used by eukaryotic cells to prevent chromosomal translocation and malignant transformation.

Mon projet ATIP-Avenir

Post-transcriptional control of the antibody response and B-cell lymphomagenesis

Development of an effective adaptive immune response is essential for fighting infections and for successful vaccination strategies that protect us against common pathogens. Activation of T and B lymphocytes is central in the adaptive immune response, and their differentiation into memory and plasma cells secures long-term life protection. Understanding the genetic mechanisms controlling lymphocyte development and function is the base of our research.

Genetic information encoded by our genes controls all aspects of the immune response. DNA is finely transcribed into messenger RNA (mRNA) that is then translated into the proteins that modulate immunity. Life of mRNA is complicated. Changes in the nature of its nucleotide sequence as well as changes in mRNA location and stability determine protein abundance and function in immune cells. Timely control of mRNA interaction with RNA binding proteins is essential for mRNA synthesis, editing and translation and for healthy immunity. Our research aims to understand how these RNA binding proteins control fundamental aspects in lymphocyte development and differentiation and how do they prevent B- cell tumour transformation. Our research is divided in three main axis.

Axis 1: Understand how post-transcriptional regulation controls the germinal centre reaction

Axis 2: Post-transcriptional mechanisms for oncogene expression during the genotoxic stress response

Axis 3: Development of new tools for transcriptome and translatome analysis in lymphocytes