Project Grant R01HL174432
- This federal Project Grant award of $663,578 from the National Heart Lung and Blood Institute (CFDA 93.837 - Cardiovascular Diseases Research) supports research at the University of Washington to address challenges in the diagnosis and treatment of cardiac sarcoidosis (CS). The key goals are to: Develop improved diagnostic methods to distinguish true CS from genetic cardiomyopathies and "idiopathic 18FDG-avidity" in 200 patients, through systematic PET imaging, genetic testing, and...
- The Project Grant award of $197,640 from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research Federal Grant Program (CFDA 93.855), aims to decipher the interactions between human T cells and cardiomyocytes in immune checkpoint inhibitor-related myocarditis. The principal investigator, Dr. Steven Blum of Massachusetts General Hospital, will utilize patient samples and human models to determine the drivers of this severe...
- This federal Project Grant award from the National Heart Lung and Blood Institute (CFDA Program 93.837 Cardiovascular Diseases Research) provides $173,480 to the University of Illinois to conduct research on the inflammatory-fibrotic axis in pulmonary sarcoidosis. The research aims to elucidate the mechanisms by which circulating CD14+ monocytes drive the inflammatory-fibrotic progression in advanced pulmonary sarcoidosis-related fibrosis (APSF). Key activities include using single-cell RNA...
- This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI), under the Cardiovascular Diseases Research program (CFDA 93.837), provides $778,266 to the Oklahoma Medical Research Foundation (OMRF) to conduct multi-omic research on sarcoidosis. The project aims to advance understanding of the mechanisms underlying sarcoidosis susceptibility and disease burden, with a focus on using high-throughput plasma proteomics from over 1,000 sarcoidosis patients to distinguish disease...
- This federal Project Grant award from the National Heart, Lung, and Blood Institute (CFDA 93.837 - Cardiovascular Diseases Research) to The Washington University is providing $112,822 to investigate the role of dendritic cell lysosome activity in immune checkpoint inhibitor-associated myocarditis. The key research objectives are to: 1) Characterize differences in lysosomal activity between wild-type dendritic cells and dendritic cells deficient in the PD-1 immune checkpoint receptor, and...
- The federal Project Grant award of $760,374 from the National Heart Lung and Blood Institute (CFDA 93.837 Cardiovascular Diseases Research) is supporting research by National Jewish Health to develop predictive molecular signatures for diagnosing sarcoidosis and identifying patients at risk of disease progression. The project will integrate single nucleotide polymorphisms, gene expression, and plasma metabolomics/lipidomics data using advanced machine learning to identify potential biomarkers....
- The National Heart, Lung, and Blood Institute (NHLBI) awarded a $773,843 Project Grant under the Cardiovascular Diseases Research program (CFDA 93.837) to The Leland Stanford Junior University (Stanford University) to develop a targeted therapy for immune checkpoint inhibitor-induced myocarditis (ICIM). The project aims to investigate the role of the CXCR3 chemokine receptor pathway in ICIM pathogenesis and evaluate a CXCR3 blocking therapy to mitigate this life-threatening side effect of cancer...
- This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research Federal Grant Program (CFDA 93.855), provides $761,840.00 to characterize the plasma cells infiltrating cardiac allografts during cardiac allograft vasculopathy (CAV) in heart transplant patients. The research aims to use advanced immunoglobulin gene repertoire analysis and single-cell sequencing techniques to comprehensively profile the plasma cells...
- The Project Grant award of $858,186, funded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), supports research to decipher the mechanisms leading to immune checkpoint inhibitor (ICI)-induced myocarditis and identify better mitigation strategies. The research leverages preliminary single-cell RNA sequencing data to analyze T cell clonotypes, biology, and predictive biomarkers associated with this fatal...
- This Project Grant award from the National Heart Lung and Blood Institute (CFDA 93.837 Cardiovascular Diseases Research) provides $249,000.00 to National Jewish Health to identify common and distinct metabolic and proteomic pathways associated with inflammation and fibrosis in pulmonary sarcoidosis. The research aims to understand whether fibrotic and non-fibrotic pulmonary sarcoidosis share common metabolic and proteomic pathways related to fibrosis and/or immunity and inflammation. The award...
INVESTIGATING CXCR3 BLOCKADE AS PRECISION THERAPY FOR CARDIAC SARCOIDOSIS USING SINGLE-CELL MULTI-OMICS AND TCR PHENOTYPING - PROJECT SUMMARY/ABSTRACT SARCOIDOSIS, CHARACTERIZED BY NON-CASEATING GRANULOMAS, IS A MULTI-ORGAN INFLAMMATORY DISEASE DISPROPORTIONATELY AFFECTING BLACK PATIENTS IN THE UNITED STATES. ALTHOUGH CARDIAC SARCOIDOSIS OCCURS IN 20-30% OF ALL PATIENTS WITH SARCOIDOSIS, IT CONTRIBUTES TO 85% OF DEATHS BY CAUSING HEART FAILURE, VENTRICULAR ARRHYTHMIAS, AND SUDDEN CARDIAC DEATH. THE LACK OF THERAPEUTIC TARGETS FOR CARDIAC SARCOIDOSIS REMAINS A SIGNIFICANT GAP IN CLINICAL CARE. MY PRIOR WORK HAS FOCUSED ON UTILIZING SINGLE-CELL MULTI-OMICS AND MASS CYTOMETRY (CYTOF) TO IDENTIFY PATHOGENIC ANTIGEN-SPECIFIC T-CELL SUBSETS IN MYOCARDITIS DUE TO CANCER IMMUNOTHERAPY. NOW, I AM EXCITED TO PIVOT MY RESEARCH DIRECTION AND EXTEND THESE INNOVATIVE METHODS TO INVESTIGATE CARDIAC SARCOIDOSIS, WITH THE GOAL OF BRINGING MY PRIOR EXPERIENCE WITH DEEP IMMUNOPHENOTYPING TOOLS TO HELP BRIDGE THE TRANSLATIONAL GAP IN CARDIAC INFLAMMATORY DISEASES. DYSREGULATION IN CD4 T-HELPER CELL (TH) SUBSETS, PARTICULARLY TH17.1 EXPRESSING C-X-C MOTIF CHEMOKINE RECEPTOR 3 (CXCR3), HAS BEEN ASSOCIATED WITH A NUMBER OF INFLAMMATORY DISEASES, INCLUDING SARCOIDOSIS. I HYPOTHESIZE THAT CARDIAC SARCOIDOSIS IS ASSOCIATED WITH RECRUITMENT OF CXCR3+ TH17.1 CELLS TO THE HEART, WHICH CAN BE THERAPEUTICALLY TARGETED WITH CXCR3 BLOCKADE. TO TEST THIS, I WILL UTILIZE A MOUSE MODEL OF CARDIAC SARCOIDOSIS AND BIOBANK SAMPLES FROM PATIENTS WITH CARDIAC AND NON-CARDIAC PULMONARY-ONLY SARCOIDOSIS COMPARED TO HEALTHY CONTROLS. IN AIM 1, I WILL PERFORM SINGLE-CELL RNA-SEQ, TCR-SEQ, AND CITE-SEQ ON TISSUE (HEART, BLOOD, LYMPHOID ORGANS, LUNGS) ISOLATED FROM TSC2FL/FL CD11C CRE+ MICE WITH CARDIAC SARCOIDOSIS. IN AIM 2, I WILL CONDUCT SINGLE-CELL MULTI-OMICS AND DEEP T-CELL PHENOTYPING ON SPECIMENS BIOBANKED FROM PATIENTS WITH CARDIAC SARCOIDOSIS COMPARED TO PULMONARY-ONLY SARCOIDOSIS AND HEALTHY CONTROL PATIENTS. IN AIM 3, I WILL EXPLORE THE THERAPEUTIC EFFECTS OF CXCR3+ BLOCKADE ON T-CELL MIGRATION. SPECIFICALLY, AIM 3A, I WILL INVESTIGATE THE MECHANISTIC EFFECTS OF BLOCKING CXCR3 AND ITS LIGANDS, CXCL9/10, ON MACROPHAGE- MEDIATED TH17.1 CELL MIGRATION AND FUNCTION IN AN IN VITRO TRANSWELL SYSTEM, WHILE IN AIM 3B I WILL TREAT TSC2FL/FL CD11C CRE+ MICE WITH CXCR3 BLOCKADE TO ASSESS FOR REDUCED CARDIAC GRANULOMA FORMATION AND TH17.1 CELL MIGRATION TO THE HEART ASSESSED BY SINGLE-CELL MULTI-OMICS. BY COMPLETING THIS PROJECT, I WILL DEFINE KEY PATHOGENIC T-CELL SUBSETS AND INTERACTIONS BETWEEN ADAPTIVE AND INNATE IMMUNITY THAT DRIVE CARDIAC SARCOIDOSIS, AND TEST A POTENTIAL THERAPEUTIC PATHWAY FOR PRECISION MEDICINE. IN DOING SO, I HOPE TO PAVE THE WAY FOR THE DEVELOPMENT OF ADJUVANT THERAPIES FOR TREATMENT AND PREVENTION OF CARDIAC SARCOIDOSIS. THIS KATZ R01 WILL BE INSTRUMENTAL IN LAUNCHING MY CHANGE IN RESEARCH DIRECTION WITHIN CARDIO-IMMUNOLOGY.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $745.2k | 7/14/25 | ||
| Not listed | $752.0k | 7/26/24 |