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Peter J. McGuire, M.D.

Head, Immunometabolism Unit, Physician Scientist Development Program
Physician Scientist, Medical Genomics and Metabolic Genetics Branch

Scientific Summary

The Immunometabolism Unit, established under the Physician Scientist Development Program, studies the interplay between metabolism and the immune system through a translational research program involving patients with inborn errors of metabolism (IEM). The group studies two aspects of immunometabolism: 1) the effects of immune system activation on end-organ metabolism; and 2) the role of intermediary metabolism in immune cell function.

The focus of the group's research on immune system activation and end-organ metabolism in IEM is based on the clinical observation that infection is a major cause of acute metabolic instability and associated morbidity and mortality in patients with IEM. The Immunometabolism Unit uses animal models, combined with infectious organisms or immune activators, to yield insights into the metabolic perturbations seen in IEM and to identify potential targets for intervention. Metabolic perturbations are demonstrated using metabolomics, mRNA profiling, proteomics, enzymology and in vivo metabolic imaging with MR spectroscopy.

In vivo metabolic imaging of hepatic pyruvate dehydrogenase activity in WT mice using MR spectroscopy with hyperpolarized 13C-pyruvate during a systemic immune challenge with Poly I:C.

The group also studies intermediary metabolism and immune cell function. Immune cells drastically alter their metabolic programming during activation and differentiation. The enzyme deficiencies present in IEM patients may affect these processes. In order to describe the interactions between intermediary metabolism and immune system function, the group developed a clinical protocol in the National Institutes of Health (NIH) Clinical Center, called the NIH MINI Study: Metabolism Infection and Immunity in IEM (NIH Clinical Trial NCT01780168).

This protocol is the first organized effort, in conjunction with the Center for Human Immunology at the NIH, to examine immune function in IEM. These investigations are complemented by concurrent studies of immune function using animal models of IEM. By expanding the immune phenotype of patients with IEM, these studies will have an impact on the clinical care of patients as well as serving as the foundation for understanding the role of intermediary metabolism in immune function.  

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Posted: November 25, 2014