Fall 2024
By Kathy Clute
Photography by John Deputy
Immunometabolism is a relatively new field that explores how cellular metabolism and metabolites influence the identity and function of immune cells. The ability to understand and manipulate immunometabolism is emerging as an important frontier that touches many diseases and cell types, including how resident immune cells known as macrophages, or white blood cells, are altered in a tumor’s microenvironment.
With funding from a Chan Zuckerberg Initiative (CZI) Measuring Metabolism Across Scales grant, Dana-Farber immunologist Evanna Mills, PhD, and co-investigator Edward Chouchani, PhD, hope to better understand how metabolites of tissue-based immune cells cause inflammation that can lead to cancer.
“Understanding metabolism is a key component of unlocking the mysteries of the cell,” said Jonah Cool, PhD, senior science program officer of CZI’s Cell Science program. “Mills’ and Chouchani’s work has been important in advancing the field to date and is now poised to accelerate how we measure human biology and understand disease.”
The initiative’s Cell Science program supports interdisciplinary collaborations to delve deeply into cell biology. The program also facilitates the creation of new technologies for engineering and investigating complex cellular systems.
“Mills’ and Chouchani’s work is now poised to accelerate how we measure human biology and understand disease.”
Jonah Cool, PhD, Chan Zuckerberg Initiative
“We want to know how cellular metabolism and metabolites influence macrophages and contribute to the development of disease,” said Mills. “And ultimately, how can we fine-tune the signaling to regulate pathologies? This could be an underappreciated frontier that could work in parallel with existing therapies.”
Tissue-resident macrophages (TRMs) are anatomically and functionally diverse, so the lab will investigate the extracellular metabolite environment that surrounds them, as well as their intracellular metabolite signature.
Using newly developed mass spectrometry techniques, Mills’ team will analyze the interstitial fluid found in the spaces between cells in diverse TRMs to compile an atlas of metabolite-protein interactions. “This could provide a tangible platform and resource to pursue new therapeutic targets with which to treat metabolic and inflammatory diseases, including cancer,” said Mills.