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Principal Investigator: Gianna Elena Hammer
Organization: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
Fiscal Year: 2024
Award: $231,000
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
Mechanisms driving inflammation, and the possibilities for therapeutic intervention, have expanded dramatically
since the discovery that the intestine is linked to inflammatory diseases involving non-intestinal organs. The
processes and cell types underpinning this inter-organ link are poorly understood, even for diseases which are
coincident with intestinal inflammation. One prominent disease with clear links to intestinal inflammation is
primary sclerosing cholangitis (PSC), an immune-mediated disease hallmarked by liver fibrosis. There is no
therapy that prevents PSC from getting worse, and liver transplant is the only cure—although sometimes, PSC
can return even after liver transplant. The driving forces behind PSC-linked liver fibrosis are thought to originate
in the intestine and thus, understanding the inflammatory processes that link intestinal inflammation with liver
fibrosis would be a breakthrough for this disease. Moreover, these fundamental discoveries would shine new
light into processes that link the intestine to inflammation involving non-intestinal organs, an area that holds
potential for transformative therapeutics. This project will unlock some of this potential by dissecting cellular
mechanisms linking intestinal inflammation with liver fibrosis in a novel mouse model where these diseases occur
concomitantly. These studies will offer specific cell types for targeted approaches to treat diseases linked to the
intestine, including PSC-linked liver fibrosis, an unstoppable disease that has no cure.
Terms: <Abdomen><Animal Model><Animal Models and Related Studies><Area><Attenuated><Automobile Driving><Bile Duct Obstruction><Biliary><Biliary Stasis><Body Tissues><Cell Body><Cell Locomotion><Cell Migration><Cell Movement><Cells><Cellular Migration><Cellular Motility><Cholangitis><Cholestasis><Data><Dendritic Cells><Disease><Disorder><Emigrant><Emigrations><Fibrosis><Health><Hepatic Disorder><Hepatic Transplantation><Histologic><Histologically><Histopathology><Human><IRF4><IRF4 gene><Immigrant><Immune><Immunes><Inflammation><Inflammatory><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Injury to Liver><Interferon Regulatory Factor 4><Intestinal><Intestinal Diseases><Intestinal Disorder><Intestines><LSIRF Protein><Label><Learning><Lifting><Light><Link><Liver><Liver Fibrosis><Liver Grafting><Liver Transplant><Liver diseases><Lung><Lung Respiratory System><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic nodes><Mediating><Methods><Mice><Mice Mammals><Migrant><Modeling><Modern Man><Multiple Myeloma Oncogene 1><Murine><Mus><Necrosis Induction><Operative Procedures><Operative Surgical Procedures><Organ><Pathogenesis><Pathologic><Pathology><Photoradiation><Poison><Population><Predisposition gene><Process><Publishing><Role><Surgical><Surgical Interventions><Surgical Procedure><Susceptibility Gene><Testing><Therapeutic><Therapeutic Intervention><Tissues><Toxic Chemical><Toxic Substance><Veiled Cells><attenuate><attenuates><bile obstruction><bile occlusion><bowel><bowel inflammation><cell motility><cell type><cholestatic diseases><cholestatic disorder><cholestatic liver disease><cholestatic liver disorder><cholestatic syndromes><co-morbid><co-morbidity><comorbidity><disease model><disorder model><driving><driving force><fibrotic liver><gut inflammation><gut-liver axis><hepatic body system><hepatic damage><hepatic disease><hepatic fibrosis><hepatic injury><hepatic organ system><hepatopathy><high reward><high risk><inflamed bowel><inflamed gut><inflamed intestine><inflammatory disease of the intestine><inflammatory disorder of the intestine><innovate><innovation><innovative><intervention therapy><intestinal autoinflammation><intestinal inflammation><intestine disease><intestine disorder><langerin><liver damage><liver disorder><liver injury><liver transplantation><lymph gland><lymph nodes><lymphnodes><migration><model of animal><mouse model><murine model><new approaches><novel><novel approaches><novel strategies><novel strategy><pathogen><predisposing gene><prevent><preventing><primary sclerosing cholangitis><pulmonary><radiologist><social role><surgery><susceptibility allele><susceptibility locus><susceptibility variant><toxic compound>