The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
Abstract Sphingolipids play significant roles in mediating inflammation in disease. Patients with inflammatory bowel disease (IBD) and colitis associated cancer (CAC) demonstrate elevated expression of various sphingolipid metabolism enzymes. Acid ceramidase (AC) is highly expressed in disease and deacylates ceramide generating the product for the generation of the bioactive lipid sphingosine 1-phosphate (S1P). Samples from patients with IBD and colorectal cancer, and animal models of colitis, have identified tissue infiltrating macrophages to be a likely source of elevated AC expression; however, the role of AC and immune cell sphingolipid metabolism in IBD remains understudied. The goal of this proposal aims to elucidate the role of myeloid cell derived AC in the progression of IBD and determine the role of AC in immune cell recruitment in IBD. Several studies have implicated sphingolipid metabolism in IBD and CAC using genetic manipulation or pharmacologic inhibitors in mouse models. Many of these studies have examined total body knockouts; however, the contribution of immune cell specific sphingolipid metabolism has not been thoroughly investigated. Our lab has demonstrated that loss of AC in myeloid cells protected mice from acute colitis using dextran sulfate sodium (DSS). The preliminary data presented in this proposal have extended these studies assessing myeloid specific loss of AC in a model of chronic colitis utilizing IL-10 deficient mice. The loss of AC protected from colonic inflammation, increased ceramide content, and reduced innate immune cell infiltrate. Furthermore, loss of AC in myeloid cells altered adaptive immune cell populations in the colon and peripheral tissues, potentially indicating a role for AC in cell- to-cell communication. Our findings have led us to hypothesize that loss of AC in myeloid cells impairs inflammatory signaling, and immune cell recruitment or maturation to alleviate chronic colitis. We therefore propose the following specific aims: Specific Aim 1: Determine the mechanism by which loss of AC protects from chronic colitis. Specific Aim 2: Determine the role of AC in T cell maturation and immune cell recruitment in colitis.
Grant Summary
The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $50K for university, nonprofit, healthcare org. Applications are due 2028-05-14 (open). Check eligibility and apply with FindGrants.
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Up to $50K
2028-05-14
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The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation: Frequently Asked Questions
Who is eligible for the The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation?
The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
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The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation provides up to $50K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation deadline?
Applications for The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation are due 2028-05-14 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation?
To apply for The Impact of Acid Ceramidase in Myeloid Cells on Intestinal Inflammation, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.