Project Details
Projekt
Augmenting RNA Modifications to Optimize Resilience against Skin Cancer -- ARMOR
Subject Area
Dermatology
Cell Biology
Cell Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 560052391
N6-methyladenosine (m6A) is a prevalent chemical modification found in most mRNAs. Gene-specific m6A modification profiles regulate mRNA stability and translation efficiency, and play important roles in melanoma tumorigenesis and the response to targeted therapies including immune checkpoint inhibition. How precisely this nucleotide modification controls cell type-specific gene regulatory programmes within a tumour microenvironment to stimulate or inhibit anti-tumour immunity remains unclear. Here, we propose harnessing m6A functions to boost the body’s immune cell responses against tumours by addressing two outstanding questions in the field. First, does inhibition of m6A formation affect tumour and immune cell functions differently? Second, how do cell type-specific changes in m6A modification levels shape the tumour microenvironment to modulate cell communication between tumour and immune cells? Together, this interdisciplinary project will functionally explore how m6A modification profiles intersect transcriptional and translational processes in a cell type- and context-specific manner to promote cancer cell survival. Objective 1 explores cell intrinsic m6A functions by deciphering how mRNA methylation levels regulate gene expression in healthy and malignant melanocytes and immune cells. Objective 2 tests the function of the m6A modification in shaping the microenvironment and facilitating communication between tumour and immune cells. Objective 3 evaluates how the m6A modification and its regulatory proteins can be used to predict patient prognosis and therapy outcome. Together, ARMOR will uncover the precise molecular mechanisms by which m6A regulates melanoma development and its tumour immune microenvironment. This knowledge is required for successfully targeting m6A in cancer therapies or using the modification as a biomarker for disease prognosis and treatment outcome.
DFG Programme
Reinhart Koselleck Projects
