Studies of immunometabolism to find new treatment strategies for chronic inflammatory diseases

Chronic inflammatory diseases represent a significant cause of morbidity and mortality across the world. Their etiology remains incompletely understood and therapeutic management is unsatisfactory.

Emerging evidence demonstrates that metabolism is a key regulator of inflammatory processes, and that a specialized metabolic state of anaerobic glycolysis, known as the Warburg effect, is central to this, as it allows M1 macrophages, Dendritic cells, and proliferating T cells to produce inflammatory cytokines and undergo rapid cell proliferation.

In contrast, the function of other immune cells, including anti-inflammatory M2 macrophages, memory T cells and T regs, is characterized by an OXPHOS-dependent metabolism.

We have uncovered a hitherto poorly studied protein tyrosine phosphatase, PTPMT1, as a key player in regulating the activity of Complex II of the ETC to mediate establishment of the Warburg effect.

This project will characterize this newly discovered effector and its interaction with complex II, and determine how complex I and II responds to cellular signaling pathways to regulate cellular energy metabolism, and how this functions during inflammation.

The results of this study will contribute to determining how inflammation is metabolically regulated at the molecular level, with the goal of informing metabolic intervention into chronic inflammatory conditions. Ultimately, we hope to reveal new treatment strategies for chronic inflammatory diseases.