Adrian Gombart

Our research is focused on understanding the regulation of antimicrobial peptide expression by the vitamin D pathway. When immune cells called macrophages encounter a pathogen and become activated, the vitamin D pathway is turned on, leading to the induction of the cathelicidin antimicrobial peptide if serum levels of vitamin D are sufficient. We have shown that this mechanism is conserved in humans and primates but not in other mammals. Therefore, we developed a transgenic mouse that carries the human cathelicidin gene. Using this model, we are testing the ability of vitamin D to protect against infection by influenza, Salmonella, and Mycobacterium tuberculosis.

Another focus of our research is to identify additional dietary compounds that regulate the expression of the cathelicidin gene. This gene is also induced by sodium butyrate and lithocholic acid, which functions through the vitamin D receptor. Nutrients that bind the vitamin D receptor may modulate the immune system by inducing the cathelicidin gene. We discovered that curcumin in curry modestly induces expression of the cathelicidin gene, which could protect the gut from infection.

Finally, we are interested in determining the effect of vitamin D on the function of the innate immune system in the elderly. Aging is accompanied by low-grade, chronic, systemic inflammation, and vitamin D has important anti-inflammatory properties. We want to determine if sufficient levels of vitamin D will reduce the inflammatory phenotype. We also want to determine if reversing severe deficiency will raise cathelicidin protein levels in the blood, which may reduce mortality in kidney dialysis and sepsis patients.

TECHNOLOGIES
Mouse Model for Vitamin D Regulated Antimicrobial Peptide Expression
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