This federal Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under CFDA Program 93.837 - Cardiovascular Diseases Research, provides $783,000.00 to support the "Combinatorial Design of Nonviral Base Editing Systems for Treating Cystic Fibrosis with Nonsense Mutations" research project. The key objectives are: 1) Chemical refinement of RNA-encoded adenine base editors (ABEs) to achieve optimal on-target gene-editing; 2) Development and fine-tuning of...
This $750,672 federal Project Grant award, issued by the National Heart Lung and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), will support research to identify cellular quality control machinery that promotes or degrades the CFTR protein in cystic fibrosis patients. The research will use leading-edge CRISPR-based pharmacogenomic analysis to comprehensively map the protein quality control systems that govern CFTR variant stability in the presence and...
This Project Grant award of $629,319.00 from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) supports research to identify cellular targets that may ameliorate cystic fibrosis (CF) disease caused by premature termination codon (PTC) variants in the CFTR gene. The study aims to ascertain the effects of ribosomal protein inhibition on CFTR PTC biogenesis, define the mechanisms by which silencing ribosomal proteins alters...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) provides $2,519,726 to the Arkansas Children's Research Institute (ACRI) to conduct a comprehensive study on cystic fibrosis (CF) treatment optimization. The key objectives are to: Analyze the population pharmacokinetics of the triple combination therapy (TC) for CF, including elexacaftor, tezacaftor, and ivacaftor, to determine drug exposure and...
This federal Project Grant award of $730,494 from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) is focused on understanding the mechanisms linking the cystic fibrosis transmembrane conductance regulator (CFTR) gene to dysregulated barrier function, insulin receptor function, and glucose transport in the lungs of cystic fibrosis (CF) patients. The research aims to identify how the expression of mutant CFTR impacts insulin...
This $2,000,987 federal Project Grant award from the National Heart, Lung, and Blood Institute (CFDA 93.837 Cardiovascular Diseases Research) supports research to understand how viral-bacterial co-infections impact chronic lung disease in cystic fibrosis (CF) patients. The project aims to elucidate how the antiviral interferon response and associated metabolic changes in the respiratory epithelium promote Pseudomonas aeruginosa biofilm formation, leading to persistent infections in CF. The...
This $653,854 Project Grant was awarded by the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837). The purpose of the grant is to study the impact of cardiomyocyte-selective modulation of natriuretic peptide signaling pathways on cardiomyopathy progression and ventricular arrhythmia susceptibility in preclinical models. The specific aims are to: 1) Define how cardiomyocyte-specific modulation of PKG1 activity modifies cardiomyopathy...
This $782,362 Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) supports research to investigate the role of TREK-1 potassium channels in acute respiratory distress syndrome (ARDS). The key objectives are to: 1) determine if ARDS decreases epithelial and endothelial TREK-1 levels, leading to cell membrane depolarization and calcium-dependent inflammation, and 2) evaluate if activating residual TREK-1...
The University of Vermont & State Agricultural College was awarded a $161,948 Project Grant by the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837). The grant supports research to elucidate the mechanisms by which capillary ATP-sensitive potassium (KATP) channels in the brain regulate cerebral blood flow in response to hypoxia. The project aims to: 1) determine how capillary KATP channels increase blood flow during hypoxic...
This federal Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI), under the Cardiovascular Diseases Research program (CFDA 93.837), provides $458,767 to The Johns Hopkins University from June 2025 through March 2029. The project aims to elucidate the ionic and molecular mechanisms underlying the regulation and dysregulation of vagal visceral nociceptor excitability, with the goal of identifying novel therapeutic strategies to reduce the suffering associated with...
This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), under the Cardiovascular Diseases Research program (CFDA 93.837), provides $2,389,542 to the University of Pittsburgh to conduct research on the mechanisms by which cystic fibrosis (CF) drug modulators affect potassium (K+) channel function.
The key objectives of the research are to: 1) Define how CF drug correctors, such as VX-445 (elexacaftor), inhibit the intermediate-conductance calcium-activated K+ channel (KCa3.1) and affect chloride (Cl-) secretion in human bronchial epithelial cells; 2) Determine the mechanisms by which CF drug correctors potentiate the large-conductance calcium-activated K+ channel (BKCa) and the resulting effects on cell physiology; and 3) Investigate the impact of CF drug corrector-mediated KCa3.1/KCa2.X inhibition and BKCa potentiation on vascular reactivity and neuronal action potential firing. The award period is from August 1, 2024 to April 30, 2028.