A5054341783- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Nitric Oxide and Endothelin Effects
- Blood groups and transfusion
- Renin-Angiotensin System Studies
- Epigenetics and DNA Methylation
- Cardiac tumors and thrombi
- Hematological disorders and diagnostics
- Erythrocyte Function and Pathophysiology
- CRISPR and Genetic Engineering
- Blood disorders and treatments
- Sodium Intake and Health
- RNA regulation and disease
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Circadian rhythm and melatonin
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA and protein synthesis mechanisms
- Chronic Myeloid Leukemia Treatments
- Renal Diseases and Glomerulopathies
- Immune responses and vaccinations
Vanderbilt University Medical Center
2018-2025
Vanderbilt-Ingram Cancer Center
2024
Vanderbilt University
2022-2024
University of Malawi
2018-2019
Augusta University
2013-2018
Georgia Regents Medical Center
2013-2014
Augusta University Health
2012
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued inflammatory gene modifier scan for CHIP-associated CVD among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data blood DNA and modeled both as a composite common drivers (DNMT3A, TET2, ASXL1, JAK2) separately. developed predicted expression scores 26 inflammasome-related genes assessed...
Clonal hematopoiesis (CH) is an age-associated phenomenon that increases the risk of hematologic malignancy and cardiovascular disease. CH thought to enhance disease through inflammation in peripheral blood.1 Here, we profile blood gene expression 66 968 single cells from a cohort 17 patients with 7 controls. Using novel mitochondrial DNA barcoding approach, were able identify separately compare mutant Tet methylcytosine dioxygenase 2 (TET2) methyltransferase 3A (DNMT3A) nonmutant...
Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk atherosclerotic cardiovascular disease. However, there are limited data regarding specific phenotypes. The purpose this study was define the coronary artery disease phenotype population-based on angiography.
Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon in which hematopoietic stem cells acquire mutations select set genes commonly mutated myeloid neoplasia then expand clonally. Current sequencing assays to detect CHIP are not optimized for the detection these variants and can be cost-prohibitive when applied large cohorts or serial sequencing. In this study, an affordable (approximately US $8 per sample), accurate, scalable assay introduced validated....
Endothelin-1 (ET-1) is increased in patients with sickle cell disease and may contribute to the development of nephropathy. The current study was designed determine whether ET-1 acting via ETA receptor contributes renal injury a mouse model disease.Adult, humanized HbSS (homozygous for Hb) mice had mRNA expression both cortex glomeruli compared heterozygous Hb A (HbAS controls). In cortex, also elevated (sickle) although ETB unchanged. Ligand binding assays confirmed that receptors vascular...
Speed JS, Hyndman KA, Roth K, Heimlich JB, Kasztan M, Fox BM, Johnston JG, Becker BK, Jin C, Gamble KL, Young ME, Pollock DM. High dietary sodium causes dyssynchrony of the renal molecular clock in rats. Am J Physiol Renal 314: F89-F98, 2018. First published September 27, 2017; doi:10.1152/ajprenal.00028.2017.-Dyssynchrony circadian rhythms is associated with various disorders, including cardiovascular and metabolic diseases. The cell autonomous maintains control; however, environmental...
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is a common form age-related somatic mosaicism that associated with significant morbidity and mortality. CHIP mutations can be identified in peripheral blood samples sequenced using approaches cover the whole genome, exome or targeted genetic regions; however, differentiating true from sequencing artifacts germline variants considerable bioinformatic challenge. We present stepwise method combines filtering based on metrics,...
Clonal hematopoiesis (CH) is an age-associated phenomenon leading to increased risk of both hematologic malignancy and nonmalignant organ dysfunction. Increasingly available genetic testing has made the incidental discovery CH clinically common yet evidence-based guidelines effective management strategies prevent adverse health outcomes are lacking. To address this gap, prospective CHIVE (clonal inflammation in vasculature) registry biorepository was created identify monitor individuals at...
This study was designed to determine whether ET-1 derived from endothelial cells contributes oxidative stress in the glomerulus of mice subjected a high-salt diet and/or hypoxia.C57BL6/J control or vascular cell knockout (VEET KO) were 3-h exposure hypoxia (8% O₂) 2 weeks (4% NaCl) prior metabolic cage assessment renal function and isolation glomeruli for determination reactive oxygen species (ROS).In mice, significantly increased urinary protein excretion during initial 24 h, but only...
The current study was designed to determine whether vascular endothelial-derived endothelin-1 (ET-1) is important for skin Na+ buffering. In control mice (C57BL/6J), plasma and osmolarity were significantly elevated in animals on high- vs. low-salt (HS LS, respectively) intake. increased associated with ET-1 mRNA tissue. There no detectable difference Na+:H2O HS fed (0.119 ± 0.005 mM 0.127 0.007 mM; LS HS); however, by blockade of the endothelin type A receptor ABT-627 (0.116 0.006 0.137 HS;...
Sickle cell disease (SCD) is among the most common inherited hematologic diseases in sub-Saharan Africa (SSA). Historically, hydroxyurea administration SSA has been restricted due to limited region-specific evidence for safety and efficacy.We conducted a prospective observational cohort study of pediatric patients with SCD Malawi. From January 2015 November 2017, at doses 10-20 mg/kg/day was administered children clinically severe (targeted use policy). December 2017 July 2018, prescribed...
Clonal hematopoiesis of indeterminate potential (CHIP) is an asymptomatic condition associated with elevated risk for myeloid neoplasms (MN). Patients CHIP and cytopenia are at greater MN. Quantifying the incidence identifying factors among patients critical improving clinical management. We analyzed sequencing data from 805,249 participants in NIH All Us Research Program (AoU), Vanderbilt's BioVU repository, UK Biobank (UKB). Genetic mutations, laboratory values, MN diagnoses were included...
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Abstract Background Glomerulopathy is an increasingly identified complication in young patients with sickle cell disease (SCD). Hyperfiltration and albuminuria followed by declining glomerular filtration rates eventual end‐stage renal (ESRD) assumed to be the typical progression of disease. There are only a few reported biomarkers identify early‐stage SCD. Procedures We detail profile 101 children SCD Malawi propose novel urinary biomarker for identification early Results Among anemia, 24.8%...
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) occurs as a result acquired mutations in bone marrow progenitor cells. CHIP confers twofold risk atherosclerotic cardiovascular disease (ASCVD). However, there is limited data regarding specific phenotypes this population. We recruited patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed next generation sequencing to determine status. Multivariable logistic regression models...
Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon that occurs when hematopoietic stem cells acquire mutations in select set genes commonly mutated myeloid neoplasia which then expand clonally. Current sequencing assays to detect CHIP are not optimized for the detection these variants and can be cost-prohibitive applied large cohorts or serial sequencing. Here, we present validate targeted assay affordable (∼$8/sample), accurate highly scalable. To...