Project Grant R01DK140072
- Federal Project Grant Award Summary Baylor College of Medicine received a $120,375 Project Grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), awarded on July 15, 2026, with a completion date of June 30, 2028. The award funds a Phase 1/2 clinical trial investigating Bifidobacterium breve supplementation in infants with cholestasis and suspected biliary atresia (BA)....
- Federal Project Grant Award Summary Baylor College of Medicine received a $215,700 Project Grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), awarded August 1, 2025, with completion expected July 31, 2027. The project will deliver research services investigating rifaximin, a non-absorbable antibiotic, as a therapeutic intervention for reducing endotoxemia and hepatic...
- Federal Project Grant Award Summary Baylor College of Medicine received a $167,165 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective July 2, 2026 through March 31, 2031. The award funds a comprehensive five-year training and research program investigating molecular mechanisms of T cell dysfunction in pediatric chronic cholestatic liver...
- Summary Boston Children's Hospital received a $133,500 Project Grant from the National Institute of Diabetes and Digestive and Kidney Diseases under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), awarded July 6, 2026, with completion targeted for April 30, 2028. The two-year research project investigates integrin αVβ6-mediated activation of latent transforming growth factor beta 2 (TGF-β2) as a driver of renal fibrosis and explores this pathway as a...
- Federal Project Grant Summary The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded the Regents of the University of Colorado–Denver a Project Grant in the amount of $775,293 on June 15, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847). The research project, titled "Defining the Role for Polyamines in Cholestatic Liver Disease," extends through February 28, 2031, and investigates the therapeutic...
- Federal Grant Award Summary Cincinnati Children's Hospital Medical Center received a $243,000 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded May 19, 2026, with completion expected April 30, 2028. The grant funds research to model fibroblast-cholangiocyte interactions in chronic ductopenic rejection (CDR), the most common immunologic cause of liver allograft loss in children....
- Federal Project Grant Award Summary Cincinnati Children's Hospital Medical Center received $851,275 in federal funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to support a research project titled "Mechanisms Regulating Competency of Hepatocyte Plasticity." The award, issued February 15, 2026, and scheduled for completion by December 31, 2029, funds...
- Federal Project Grant Award Summary Yale University received a $168,000 Project Grant from the National Center for Advancing Translational Sciences (NCATS, CFDA 93.350) effective August 1, 2026 through July 31, 2027. This high-risk, high-reward research initiative investigates the role of P2RY8, a G-protein-coupled receptor, in B cell-endothelial cell crosstalk within the context of primary biliary cholangitis (PBC), a chronic autoimmune liver disease. The project will deliver two primary...
- Summary The National Institute of Child Health and Human Development (NICHD) awarded a $324,000 Project Grant under the Child Health and Human Development Extramural Research program (CFDA 93.865) to the University of Texas Health Science Center at Houston, effective April 1, 2026, through August 31, 2031. The award funds research investigating the role of gut microbiota-derived butyrate in modulating inflammation and improving neurological outcomes following neonatal hypoxic-ischemic...
- Grant Award Summary The National Heart, Lung, and Blood Institute (NHLBI) awarded The Children's Hospital of Philadelphia Research Institute a $1.177 million Project Grant on August 10, 2025, under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct basic biomedical research on the origins and mechanisms of neonatal lung myofibroblasts. The research project, scheduled for completion by May 31, 2029, leverages a novel murine model to investigate how bone morphogenetic protein...
MECHANISMS OF NEUTROPHIL EXTRACELLULAR TRAP FORMATION AND CONTRIBUTION TO BILIARY FIBROSIS IN BILIARY ATRESIA - PROJECT SUMMARY/ABSTRACT BILIARY ATRESIA (BA) IS AN INFLAMMATORY, SCLEROSING LESION OF THE BILIARY TREE THAT PRESENTS IN INFANCY AND IS ASSOCIATED WITH SIGNIFICANT BILIARY FIBROSIS. THE DEGREE OF FIBROSIS AT PRESENTATION IS UNPRECEDENTED COMPARED TO ANY OTHER ORGAN-SPECIFIC DISEASE OF INFANCY AND THE VAST MAJORITY OF BA PATIENTS WILL NEED LIVER TRANSPLANTATION FOR SURVIVAL. VARIOUS IMMUNE PATHWAYS HAVE BEEN IMPLICATED IN CHOLANGIOCYTE INJURY IN BA, YET KEY IMMUNE PATHWAYS THAT PROMOTE FIBROSIS ARE UNKNOWN. A CRITICAL BARRIER TO DISCOVERING NOVEL THERAPIES IN BA IS THE LACK OF AN UNDERSTANDING OF KEY CELLULAR MECHANISMS PROMOTING BILIARY FIBROSIS. THE BIOMARKER CXCL8 (IL-8), A NEUTROPHIL CHEMOATTRACTANT AND ACTIVATOR, AND NEUTROPHIL EXTRACELLULAR TRAPS (NETS) HAVE BEEN PREVIOUSLY SHOWN TO PREDICT WORSE OUTCOMES IN BA. SIGNIFICANT PRELIMINARY DATA WITHIN THIS PROPOSAL REVEALS THAT NEUTROPHILS ARE CHRONICALLY ACTIVATED IN BA PATIENTS, WITH PERSISTENT CXCL8-CXCR2-MEDIATED NET FORMATION (NETOSIS). CONSTITUENTS OF BA NETS INCLUDE PRO-FIBROGENIC PROTEINS AND NETS POSITIVELY CORRELATE WITH BIOMARKERS OF INJURY AND FIBROSIS. THE HYPOTHESIS TO BE TESTED IS THAT THE IMMUNOPATHOGENESIS OF BA INVOLVES CXCL8-CXCR2-MEDIATED NETOSIS, RESULTING IN NET-INDUCED PORTAL FIBROBLAST AND STELLATE CELL ACTIVATION. THE ROTAVIRUS-INDUCED MOUSE MODEL OF BA (MURINE BA), AS WELL AS ANALYSES OF HUMAN BIOSPECIMENS, WILL BE EMPLOYED TO ADDRESS THE HYPOTHESIS. SPECIFIC AIM 1 WILL DETERMINE IF NEUTROPHIL CXCR2 ACTIVATION IS ESSENTIAL FOR NETOSIS IN MURINE BA. SPECIFIC AIM 2 WILL DETERMINE THE PREDOMINANT SOURCE OF REACTIVE OXYGEN SPECIES THAT IS NECESSARY FOR NETOSIS (NADPH-OXIDASE DEPENDENT VERSUS MITOCHONDRIAL SOURCE). SPECIFIC AIM 3 WILL ESTABLISH THE PRO-FIBROGENIC ROLE OF NETS IN BA, INCLUDING PORTAL FIBROBLAST AND HEPATIC STELLATE CELL ACTIVATION THROUGH USE OF PRIMARY CELL LINES AND HEPATIC ORGANOIDS. IMPACT. DISCOVERIES FROM THIS RESEARCH COULD BE HIGHLY IMPACTFUL, WITH INCREASED KNOWLEDGE GAINED IN NEUTROPHIL BIOLOGY AND WITH THE IDENTIFICATION OF NOVEL THERAPEUTICS TARGETING NETOSIS THAT WOULD PREVENT BILIARY CIRRHOSIS IN CHILDREN WITH BA.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $546.0k | 5/15/25 | ||
| Not listed | $546.0k | 7/19/24 | ||
| Not listed | $546.0k | 7/19/24 |