- Effects of Radiation Exposure
- Medicinal Plants and Bioactive Compounds
- Cancer Cells and Metastasis
- Phytochemical and Pharmacological Studies
- Radiation Therapy and Dosimetry
- Hydrogen's biological and therapeutic effects
- Cancer Research and Treatments
- Ultrasound and Hyperthermia Applications
- Extracellular vesicles in disease
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Mesenchymal stem cell research
- Childhood Cancer Survivors' Quality of Life
- Neurological Disease Mechanisms and Treatments
- MicroRNA in disease regulation
- Pancreatic and Hepatic Oncology Research
- Growth Hormone and Insulin-like Growth Factors
- Microbial Inactivation Methods
- Genomics, phytochemicals, and oxidative stress
- Cytokine Signaling Pathways and Interactions
- Protein Degradation and Inhibitors
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Vitamin C and Antioxidants Research
- Wnt/β-catenin signaling in development and cancer
University of Kansas Medical Center
2017-2025
The University of Kansas Cancer Center
2017-2025
Discovery Institute
2025
Sanford Burnham Prebys Medical Discovery Institute
2025
University Medical Center
2022
University Hospital and Clinics
2022
University of Kansas
2017-2021
Montefiore Medical Center
2010-2020
Albert Einstein College of Medicine
2007-2016
Yeshiva University
2015
Abstract WNT/β-catenin signalling is crucial for intestinal homoeostasis. The epithelium and stroma are the major source of WNT ligands but their origin role in stem cell (ISC) epithelial repair remains unknown. Macrophages a constituent stroma. Here, we analyse macrophage-derived mice by inhibiting release using macrophage-restricted ablation Porcupine, gene essential synthesis. Such Porcn -depleted have normal morphology hypersensitive to radiation injury intestine compared with wild-type...
Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS), resulting from direct cytocidal effects on intestinal stem cells (ISC) crypt stromal cells. We examined whether bone marrow-derived adherent cell (BMSCT) could restitute irradiated niche syndrome.Autologous marrow was...
Serum miRNAs can predict long-term radiation-induced hematopoietic injury immediately after radiation and thereby facilitate timely medical intervention improve overall survival of exposed individuals.
Background Radiation-induced gastrointestinal syndrome (RIGS) results from a combination of direct cytocidal effects on intestinal crypt and endothelial cells subsequent loss the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, infection mortality. Because R-spondin1 (Rspo1) acts as mitogenic factor for stem cells, we hypothesized that systemic administration Rspo1 would amplify accelerate regeneration irradiated intestine, thereby, ameliorating RIGS. Methods...
Tumor-initiating stem cells (TSCs) are critical for drug resistance and immune escape. However, the mutual regulations between TSC tumor microenvironment (TME) remain unclear. Using DNA-label retaining, single-cell RNA sequencing (scRNA-seq), other approaches, we investigated intestinal adenoma in response to chemoradiotherapy (CRT), thus identifying therapy-resistant TSCs (TrTSCs). We find bidirectional crosstalk TME using CellPhoneDB analysis. An intriguing finding is that shape into a...
Purpose Radiation-induced gastrointestinal syndrome (RIGS) is due to the clonogenic loss of crypt cells and villi depopulation, resulting in disruption mucosal barrier, bacterial invasion, inflammation sepsis. Intestinal macrophages could recognize invading DNA via TLR9 receptors transmit regenerative signals neighboring crypt. We therefore investigated whether systemic administration designer agonist ameliorate RIGS by activating TLR9. Methods Materials Male C57Bl6 mice were distributed...
Radiation-induced gastrointestinal syndrome (RIGS) results from the acute loss of intestinal stem cells (ISC), impaired epithelial regeneration, and subsequent mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, sepsis, mortality. The high radiosensitivity epithelium limits effective radiotherapy against abdominal malignancies survival victims nuclear accidents or terrorism. Currently, there is no approved therapy to mitigate radiation toxicity intestine. Here we...
Abstract Purpose: The radiosensitivity of the normal intestinal epithelium is major limiting factor for definitive radiotherapy against abdominal malignancies. Radiosensitizers, which can be used without augmenting radiation toxicity to tissue, are still an unmet need. Inhibition proteosomal degradation being developed as a therapeutic strategy anticancer therapy cancer cells more susceptible proteasomal inhibition–induced cytotoxicity compared with cells. Auranofin, gold-containing...
Macrophages are the major source of WNT ligands. However, regulation expression in macrophages has not been studied. In present study, we have discovered that activation canonical β-Catenin signaling suppresses macrophages. EVs from these pre-conditioned promoted intestinal stem cell regeneration and mitigated injury. ChIP-seq analysis validation studies using recombinant DNA construct expressing Luciferase reporter under promoter (e.g. WNT5a WNT9b) were conducted to demonstrate involvement...
ABSTRACT MYC-driven (MYC+) cancers are aggressive and often fatal. MYC dysregulation is a key event in these cancers, but overexpression of alone not always enough to cause cancer. Plasmocytoma Variant Translocation 1 ( PVT1 ), long non-coding RNA (lncRNA) adjacent on chromosome 8 rearrangement hotspot many MYC+ cancers. In addition being co-amplified with MYC, the genomic at involves translocation, which has had obscure functional consequences. We report that translocation locus asymmetric...
Abstract Objective Autoimmune diseases predominantly affect women, suggesting that female sex hormones may play a role in the pathogenesis of such diseases. We have previously shown persistent mild‐to‐moderate elevations serum prolactin levels induce break self tolerance mice with BALB/c genetic background. The aim this study was to evaluate effects hyperprolactinemia on mechanisms B cell induction. Methods Effects splenic subsets were studied mice. receptor (BCR)–mediated apoptosis and...
Radiation-induced rectal epithelial damage is a very common side effect of pelvic radiotherapy and often compromise the life quality treatment outcome in patients with malignancies. Unlike small bowel colon, radiation stem cells has not been explored extensively. Here we demonstrate that Lgr5-positive are radiosensitive organoid-based transplantation mitigates rectum.C57Bl6 male mice (JAX) at 24 h were exposed to irradiation (PIR) determine epithelium. Effect PIR on (RSCs) was determined...
The unfolded protein response (UPR) is an established and well-studied cellular to the stress serves relieve reinstate homeostasis.It occurs in endoplasmic reticulum (ER), responsible of properly folding processing secretory transmembrane proteins.It extremely sensitive alteration homeostasis caused by various internal or external stressors which leads accumulation misfolded proteins ER lumen.The UPR works restoring ER, either through boosting protein-folding degradation capability assuaging...
Two species of the elongation factor 1 (EF-1) differing in molecular weight, subunit composition, and isoelectric point have been isolated from cell-free extracts yeast Saccharomyces cerevisiae. The ratio these two forms EF-1 activity (EF-1 alpha EF-1H) seem to vary different strains upon growth phase which cells isolated. log a protease negative strain EJ101 show distribution EF-1H 3:1. Another laboratory strain, D-587-4B, shows pattern 4:1. are completely separable by ion exchange, gel...
The hypoxic tumor microenvironment generates oxidative Endoplasmic Reticulum (ER) stress, resulting in protein misfolding and unfolded response (UPR). UPR induces several molecular chaperones including heat-shock 90 (HSP90), which corrects improves survival of cancer cells resistance to tumoricidal therapy although prolonged activation cell death. HSP90 inhibitor, 17AAG, has shown promise against various solid tumors, prostate (PC). However, therapeutic doses 17AAG elicit systemic toxicity....
Abstract We previously reported that ionizing radiation (IR) mediates cell death through the induction of CUGBP elav‐like family member 2 (CELF2), a tumor suppressor. CELF2 is an RNA binding protein modulates mRNA stability and translation. Since IR induces autophagy, we hypothesized regulates autophagy‐mediated colorectal cancer (CRC) death. For clinical relevance, determined levels in The Cancer Genome Atlas (TCGA). Role response was carried out CRC lines by immunoblotting,...