Project Details
Projekt
MALT1 signaling network in B cell metabolism and function
Subject Area
Immunology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 505372148
Cancer cells are in general characterized by a high need for biosynthetic precursor molecules and energy to drive malignant proliferation. Nevertheless, in B cell lymphoma the metabolic signatures can differ between subentities reflecting their genetical and biological heterogeneity. While it is still largely unclear how distinct oncogenic signaling pathways shape B cell lymphoma metabolism, the identification of these mechanisms can provide new biomarkers for disease stratification and targets for treatment. In previous work, we have demonstrated that the CARD11/BCL10/MALT1 (CBM) complex plays crucial roles in B cell receptor signaling during physiological and pathologic B cell activation and in lymphomagenesis. Furthermore, we found that the enforced expression of an oncogenic CARD11 gain-of-function mutation, isolated from human diffuse large B cell lymphoma, drives malignant B cell hyperproliferation in murine models. We have also dissected the different contributions of the MALT1 effector protein during this process and obtained evidence that this pathway mediates B cell metabolic reprogramming. Here we want to gain precise mechanistic understanding of CBM-dependent metabolic control in normal and malignant B cell function and to establish how these metabolic features contribute to B cell proliferation, stress responses and survival. To this end, we will use state-of-the-art experimental methods such as desorption electrospray ionization mass spectrometry (DESI-MSI) and rapid evaporative ionization mass spectrometry (REIMS) not only to study intracellular metabolic states but also to extend our analysis to the microenvironment. Understanding how normal B cell activation and oncogenically hard-wired B cells affect the composition of their micromilieu could also have broad implications for the function of bystander cells in the micromilieu.
DFG Programme
Research Units
