mghlogoMIBRClogomghfc-logohms-logo

MIBRC Research

Principal Investigators:

Bobby Cherayil, MD >>

Alessio Fasano, MD

Verena Göbel, MD

Bryan Hurley, PhD

Hai Ning Shi, DVM, PhD

W. Allan Walker, MD

Collaborators:

Beth McCormick, PhD

Hans-Christian Reinecker, MD

Research Lab

Bobby Cherayil, MD

Immunologist, Massachusetts General Hospital
Associate Professor of Pediatrics, Harvard Medical School

Phone: (617) 726-4170
FAX: (617) 726-4172
Email: cherayil@helix.mgh.harvard.edu

Research Team:

Ling-lin Fu, Visiting Scientist
Nanda Kumar N. Shanmugam, Post-Doctoral Fellow
Estela Trebicka, Research Technician

Iron, Infection, Inflammation

Dr. Bobby Cherayil’s laboratory uses a combination of in vitro tissue culture strategies and in vivo mouse experiments to study how innate immune responses are influenced by host and environmental factors. Over the last 5 years, the laboratory has focused on the cross-talk between iron metabolism and inflammation, i.e., how abnormalities of iron metabolism alter innate immunity, and, conversely, how states of immune activation affect iron homeostasis.

placeholder
Salmonella typhimurium.

One of the notable findings of these experiments is that a decrease in the intracellular level of free iron in macrophages leads to an impairment of signal transduction by Toll-like receptor 4 (TLR4), the major sensor of Gram negative lipopolysaccharide. This impairment compromises the expression of inflammatory cytokines and the elimination of bacterial pathogens such as Salmonella typhimurium, an important agent of acute food poisoning in humans. The results provide insight into the well recognized but poorly understood susceptibility to infection associated with human diseases of iron metabolism such as hereditary hemochromatosis.

nanda
Nanda Kumar N. Shanmugam, Post-Doctoral Fellow

The laboratory also uses mouse models of inflammatory bowel disease (IBD) to understand how intestinal inflammation can lead to derangements of iron metabolism. This issue is of clinical importance since many chronic inflammatory conditions, including IBD, are associated with a refractory anemia known as the anemia of inflammation (AI). AI is a consequence of abnormally elevated levels of the peptide hormone hepcidin, the central regulator of systemic iron homeostasis.

Ling-lin
Ling-lin Fu, Visiting Scientist

Work from the Cherayil laboratory has shown that different cytokines produced in the inflamed colon can either up-regulate or down-regulate hepcidin expression, and that the net level of hepcidin is probably determined by the mix of cytokines that is prevalent in a given inflammatory state. Importantly, results from these experiments have shown that blocking hepcidin expression in models of IBD can have beneficial effects on both AI and intestinal inflammation itself. These findings have implications for the management of IBD and other inflammatory diseases. The studies summarized here have been supported by grants from the National Institutes of Health and private funding agencies, and the results have been published in several articles.

nanda
Estela Trebicka, Research Technician