A5085233493- Immune Cell Function and Interaction
- Acute Kidney Injury Research
- Renal Transplantation Outcomes and Treatments
- Genomics, phytochemicals, and oxidative stress
- Dialysis and Renal Disease Management
- T-cell and B-cell Immunology
- Chronic Kidney Disease and Diabetes
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Gut microbiota and health
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- Muscle and Compartmental Disorders
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Drug Transport and Resistance Mechanisms
- Renal Diseases and Glomerulopathies
- Pediatric health and respiratory diseases
- Liver Disease Diagnosis and Treatment
- Palliative Care and End-of-Life Issues
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Metabolism and Genetic Disorders
- Carcinogens and Genotoxicity Assessment
- Immune Response and Inflammation
Johns Hopkins University
2016-2025
Johns Hopkins Medicine
2016-2025
University of Baltimore
2017-2023
Pediatric Nephrology of Alabama
2019
Central Drug Research Institute
2006-2008
University of Florida
1973
T lymphocytes are established mediators of ischemia reperfusion (IR)-induced AKI, but traditional immune principles do not explain their mechanism early action in the absence alloantigen. Nrf2 is a transcription factor that crucial for cytoprotective gene expression and generally thought to have key role dampening IR-induced AKI through protective effects on epithelial cells. We proposed an alternative hypothesis augmentation cells essential mitigate oxidative stress during AKI. therefore...
Apigenin, a dietary flavonoid, is reported to have several therapeutic effects in different diseases including cancer. Toxicity of Apigenin however, least explored, and reports are scanty literature. This warrants dose-specific evaluation toxicity vivo. In the present study, was administered intraperitoneally Swiss mice at doses 25, 50, 100 200 mg/kg. Serum levels alanine amino transferase (ALT), aspartate (AST) alkaline phosphatase (ALP) were measured along with examination liver histology,...
Ischemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4+ T cells, natural killer CD4+CD25+FoxP3+ Tregs in AKI pathogenesis. We recently identified CD4−CD8− (double-negative; DN) cells as an subset αβ cell receptor–positive residing mouse kidney. However, little known about the pathophysiologic functions kidney DN cells. In this study, we phenotypically functionally characterized murine steady state response to IRI....
Significance Statement T cells mediate pathogenic and reparative processes during AKI, but the exact mechanisms regulating kidney cell functions are unclear. This study identified upregulation of novel immune checkpoint molecule, TIGIT, on mouse human after AKI. TIGIT-expressing produced proinflammatory cytokines had effector (EM) central memory (CM) phenotypes. TIGIT-deficient mice protection from both ischemic nephrotoxic Single-cell RNA sequencing led to discovery possible downstream...
Nuclear factor erythroid 2-related 2 (Nrf2) and hypoxia-inducible factor-1α (HIF1α) transcription factors protect against ischemic acute kidney injury (AKI) by upregulating metabolic cytoprotective gene expression. In this study, we tested the hypothesis that Nrf2 is required for HIF1α-mediated hypoxic responses using Nrf2-sufficient (wild-type) Nrf2-deficient ( –/– ) primary murine renal/kidney tubular epithelial cells (RTECs) human immortalized (HK2 cells) with HIF1 inhibition activation....
Background Previous studies have demonstrated that double-negative (DN) αβ T cells play an important role in immune responses during ischemic acute kidney injury (AKI). Here, we investigate the of γ-chain cytokines driving DN cell proliferation steady state and AKI, focusing on IL-2, IL-7, IL-15.
CD4+ T cells mediate the pathogenesis of ischemic and nephrotoxic acute kidney injury (AKI). However, underlying mechanisms cell-mediated are largely unknown. We therefore conducted unbiased RNA-sequencing to discover novel mechanistic pathways after ischemia compared with normal mouse kidney. Unexpectedly, lipocalin-2 (Lcn2) gene, which encodes neutrophil gelatinase-associated lipocalin (NGAL) had highest fold increase (∼60). The NGAL in during AKI was confirmed at mRNA level quantitative...
T cells play an important role in acute kidney injury (AKI). Metabolic programming of regulates their function, is a rapidly emerging field, and unknown AKI. We induced ischemic AKI C57BL/6J mice collected kidneys spleens at multiple time points. were isolated analyzed by immune-metabolic assay. Unbiased machine learning analyses identified distinct cell subset with reduced voltage-dependent anion channel 1 mTOR expression post-AKI kidneys. Ischemic showed higher trimethylation histone H3...
Invariant natural killer T (iNKT) cells recognize glycolipids as antigens and diversify into NKT1 (IFN-γ), NKT2 (IL-4), NKT17 (IL-17) functional subsets while developing in the thymus. Mechanisms that govern balance between these are poorly understood due, partly, to lack of distinguishing surface markers. Here we identify heparan sulfate proteoglycan syndecan-1 (sdc1) a specific marker naïve thymic mice show sdc1 deficiency significantly increases at expense cells, leading impaired iNKT...
Significance Statement Understanding how each immune cell type functions in the kidney is necessary to develop new immunotherapies for cell-mediated diseases, including transplant rejection, AKI, and GN. Although CD4 − CD8 double-negative (DN) T cells are a significant subpopulation that anti-inflammatory protective during ischemic little known about role of various MHC class I II molecules regulating their function. In addition showing mouse DN have IL-2–dependent proliferation, authors...
Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) proteins work in concert to regulate the levels of reactive oxygen species (ROS). The Keap1-Nrf2 antioxidant system also participates T cell differentiation inflammation, but its role innate development functions remains unclear. We report that cell-specific deletion Keap1 results defective reduced numbers invariant natural killer (NKT) cells thymus peripheral organs a cell-intrinsic manner....
T cells play pathophysiologic roles in kidney ischemia-reperfusion injury (IRI), and the nuclear factor erythroid 2-related 2/kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway regulates cell responses. We hypothesized that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated
T cells mediate organ injury and repair. A proportion of unconventional kidney called double-negative (DN) (TCR
Abstract T cells are important in the pathogenesis of acute kidney injury (AKI), and TCR + CD4 - CD8 (double negative-DN) that have regulatory properties. However, there is limited information on DN compared to traditional cells. To elucidate molecular signature spatial dynamics during AKI, we performed single-cell RNA sequencing (scRNA-seq) sorted murine DN, , combined with transcriptomic profiling normal post AKI mouse kidneys. scRNA-seq revealed distinct transcriptional profiles for...
Contractile responses of rings ductus arteriosus from fetal and neonatal guinea pigs were studied in buffered Krebs-Henseleit solutions various oxygen tensions. Oxygen-induced contraction increased with gestational age, peaking at term attenuating within 24 h after birth. Contractions response to potassium not different preterm fetuses. Maximal contractile pre- postductal aortic was 8.3% the maximal oxygen-induced ductal same Pulmonary artery quite insensitive oxygen. Of 12 exposed...