1. Host Metabolic Adaptations to Inflammation
Inflammation is a host protective response to mediate clearance of invading pathogens, irritants, or damaged cells. To fuel the inflammatory process, our body undergo metabolic adaptation to allow greater expenditure of energy. However, as in the case of low-grade chronic inflammation, the continuous metabolic burden inadvertently potentiates the development type 2 diabetes and obesity and leading to symptoms of metabolic syndrome. Hence, the primary vein of my research pertains to the interplay between intestinal inflammation and metabolic disorders. My research demonstrates that Toll-like receptor 5 (TLR5)-deficient mice prone to develop spontaneous gut inflammation. To cope up with gut inflammation, these mice adapt alternate metabolic pathways which protect against inflammation but culminates into metabolic diseases. We believe that development of metabolic syndrome in TLR5 deficient mice can be viewed as metabolic adaptation to inflammation.
2. Innate Immunity-Gut Microbiotal Interactions in Metabolic Diseases
The dynamics between innate immunity and gut microbiota frame many of my research questions. A large body of my work focuses on understanding the mechanisms by which the innate immune response helps in the gut microbiotal homeostasis. Specifically, we demonstrate that microbial products (i.e.viral RNA, flagellin) which potently activate their cognate TLR activation and broadly protect against insults such as chemicals, viruses and radiation.
3. Lipocalin 2 - mediated Iron Homeostasis in Inflammation
My research has shown that Lipocalin 2 (Lcn2), a protein elevated during the inflammatory response, can serve as a robust biomarker for intestinal inflammation. More recently, my studies have grown to encompass exploration on the role of Lcn2 in iron homeostasis during inflammation. During this endeavor, I demonstrate that Lcn2 facilitates the hypoferremia of inflammation and also protects against iron-induced toxicity. Loss of Lcn2 disrupts iron homeostasis with adverse consequences not only to the host, but also leads to gut microbiotal dysbiosis that aggravate the host’s susceptibility to colitis.