Monocytes and Cancer Metabolism

Aim: Identify functional effects of exogenous 1-MNA on primary monocytes. Study the effects of NNMT inhibition in glioblastoma cells with respect to tumour progression and interaction with immune cells.

Background: The enzyme NNMT is highly expressed in various cancers, but the underlying mechanisms for NNMT-mediated tumor progression remain elusive. The suggested mechanisms to date have largely focused on tumor-endogenous effects of NNMT, where its role as a methyl sink leads to hypomethylation of histones and DNA. However, recent studies have suggested that NNMT-expressing tumors modulate the activity of immune cells in the tumor microenvironment through secretion of the NNMT product 1-MNA.

Outcomes: By identifying the modulatory effects that 1-MNA has on primary monocytes, we would be able to strengthen the idea of NNMT as a future drug target in several cancers. The combined skills of ORU and Sprint Bioscience will generate a deeper understanding of how modulation of NNMT activity affects immune responses in tumors and how NNMT inhibitors could be used for cancer treatment.