Mechanisms of Pathogenic Metabolic Manipulation
Representation of the cellular metabolome. (Modified from the KEGG Pathway Database)
The Munger laboratory studies how viruses and cancer-causing mutations manipulate cellular metabolic processes to enable there proliferation. Both cancerous cells and viruses depend on the metabolic resources provided by the host to supply the energy and biochemical building blocks necessary for their replication. Many anti-viral and anti-cancer compounds, such as nucleotide analogs, target these parasites' utilization of cellular metabolic resources and have proven to be clinically successful. Despite these successes, very little is known about the mechanisms governing the pathogenic manipulation of the small molecule metabolic network. Our laboratory's goal is to elucidate these mechanisms and thereby identify potential therapeutic targets to block cancer and virally-associated disease. Towards the end, we couple molecular genetics with LC-MS/MS-based metabolomic analysis to probe how viral infection and cancer-causing mutations alter metabolic regulatory pathways as part of the pathogenic process. We are currently working on the following projects:
- Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells. J Biol Chem. 288, 33542-58. (2013 Nov 22).
- Inhibition of arenavirus by A3, a pyrimidine biosynthesis inhibitor. J Virol. In press. (2013 Nov 06).
- IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature. 488, 656-9. (2012 Aug 30).