A5102824031- Gut microbiota and health
- Probiotics and Fermented Foods
- Clostridium difficile and Clostridium perfringens research
- Diet and metabolism studies
- Viral-associated cancers and disorders
- Tryptophan and brain disorders
- Pharmacogenetics and Drug Metabolism
- Biochemical and Molecular Research
- Gastrointestinal motility and disorders
- Microscopic Colitis
- Cytomegalovirus and herpesvirus research
- Microtubule and mitosis dynamics
- Parasitic Infections and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- Mycobacterium research and diagnosis
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Mast cells and histamine
- Cancer, Hypoxia, and Metabolism
- Single-cell and spatial transcriptomics
- Advanced Breast Cancer Therapies
- Colorectal Cancer Treatments and Studies
- Pharmacological Effects of Natural Compounds
University of North Carolina at Chapel Hill
2016-2025
UNC Lineberger Comprehensive Cancer Center
2012-2023
The Ohio State University Wexner Medical Center
2009-2020
Segeberger Kliniken
2018
University of Mississippi Medical Center
2016
Jackson Memorial Hospital
2016
Weatherford College
2012
University of Colorado Boulder
2008-2010
The Ohio State University
2009
College of Charleston
2005
Irinotecan treats a range of solid tumors, but its effectiveness is severely limited by gastrointestinal (GI) tract toxicity caused gut bacterial β-glucuronidase (GUS) enzymes. Targeted GUS inhibitors have been shown to partially alleviate irinotecan-induced GI damage and resultant diarrhea in mice. Here, we unravel the mechanistic basis for protection microbial using vivo models. We use vitro, fimo, models determine whether inhibition alters anticancer efficacy irinotecan. demonstrate that...
Background & AimsSingle-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell covering duodenum, jejunum, ileum, ascending, transverse, descending from 3 beings.MethodsA total 12,590 single epithelial cells independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, drug...
The metabolic differences between B-NHL and primary human B cells are poorly understood. Among B-cell non-Hodgkin lymphomas (B-NHL), effusion lymphoma (PEL) is a unique subset that linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). We report the profiles of significantly different from PEL. Compared cells, both aerobic glycolysis fatty acid synthesis (FAS) up-regulated in PEL other types nonviral B-NHL. found FAS occur PI3K-dependent manner appear be interdependent....
As an obligate intracellular parasite, the Kaposi sarcoma-associated herpesvirus (KSHV) relies on host cell machinery to meet its needs for survival, viral replication, production, and dissemination of progeny virions. KSHV is a ɣ-herpesvirus that associated with three different malignancies: sarcoma (KS), two B lymphoproliferative disorders, primary effusion lymphoma (PEL) multicentric Castleman disease (MCD). proteins modulate cellular phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian...
Abstract Bacterial β-glucuronidase (GUS) enzymes cause drug toxicity by reversing Phase II glucuronidation in the gastrointestinal tract. While many human gut microbial GUS have been examined with model glucuronide substrates like p -nitrophenol-β-D-glucuronide ( NPG), orthologs that are most efficient at processing drug-glucuronides remain unclear. Here we present crystal structures of from commensals Lactobacillus rhamnosus , Ruminococcus gnavus and Faecalibacterium prausnitzii possess an...
Hormones and neurotransmitters are essential to homeostasis, their disruptions connected diseases ranging from cancer anxiety. The differential reactivation of endobiotic glucuronides by gut microbial β-glucuronidase (GUS) enzymes may influence interindividual differences in the onset treatment disease. Using multi-omic, vitro, vivo approaches, we show that germ-free mice have reduced levels active endobiotics distinct Loop 1 FMN GUS drive hormone neurotransmitter reactivation. We...
It is increasingly clear that interindividual variability in human gut microbial composition contributes to differential drug responses. For example, gastrointestinal (GI) toxicity not observed all patients treated with the anticancer irinotecan, and it has been suggested this a result of differences types levels bacterial β-glucuronidases (GUSs). GUS enzymes promote by hydrolyzing inactive drug–glucuronide conjugate back active drug, which damages GI epithelium. Proteomics-based...
Women are at significantly greater risk of metabolic dysfunction after menopause, which subsequently leads to numerous chronic illnesses. The gut microbiome is associated with obesity and dysfunction, but its interaction female sex hormone status the resulting impact on host metabolism remains unclear. Herein, we characterized inflammatory phenotypes as well ovariectomy high-fat diet feeding, compared gonadal intact low-fat controls. We then performed fecal microbiota transplantation (FMT)...
Regorafenib (Stivarga) is an oral small molecule kinase inhibitor used to treat metastatic colorectal cancer, hepatocellular carcinomas, and gastrointestinal stromal tumors. Diarrhea one of the most frequently observed adverse reactions associated with regorafenib. This toxicity may arise from reactivation inactive regorafenib-glucuronide regorafenib by gut microbial β-glucuronidase (GUS) enzymes in tract. We sought unravel molecular basis processing human intestinal GUS examine potential...
Recent advances suggest that in vivo reprogramming of endogenous cell populations provides a viable alternative for neuron replacement. Astrocytes and oligodendrocyte precursor cells can be induced to transdifferentiate into neurons the CNS, but, these instances, requires either transgenic mice or retroviral-mediated gene expression. We developed microRNA (miRNA)-GFP construct vitro significantly reduced expression polypyrimidine tract-binding protein, and, subsequently, we packaged this...
The diversity of autologous cells being used and investigated for cancer therapy continues to increase. Mast (MCs) are tissue that contain a unique set anti-cancer mediators found in around tumors. We sought exploit the anti-tumor MC granules selectively target them tumor using specific immunoglobin E (IgE) controllably trigger release upon cell engagement. human HER2/neu-specific IgE arm MCs through high affinity receptor (FcεRI). ability bind induce apoptosis HER2/neu-positive vitro vivo...
Mycophenolate mofetil (MMF) is an important immunosuppressant prodrug prescribed to prevent organ transplant rejection and treat autoimmune diseases. MMF usage, however, limited by severe gastrointestinal toxicity that observed in approximately 45% of recipients. The active form the drug, mycophenolic acid (MPA), undergoes extensive enterohepatic recirculation bacterial β-glucuronidase (GUS) enzymes, which reactivate MPA from mycophenolate glucuronide (MPAG) within tract. GUS enzymes...
We have identified another Drosophila GTP-binding protein (G protein) alpha subunit, dGq alpha-3. Transcripts encoding alpha-3 are derived from alternative splicing of the locus previously shown to encode two visual-system-specific transcripts [Lee, Y.-J., Dobbs, M.B., Verardi, M.L. & Hyde, D.R. (1990) Neuron 5, 889-898]. Immunolocalization studies using isoform-specific antibodies and LacZ fusion genes show that is expressed in chemosensory cells olfactory taste structures, including a...
Repeated exposure to a moderately intense stressor typically produces attenuation of the hypothalamic-pituitary-adrenal (HPA) axis response (habituation) on re-presentation same stressor; however, if novel is presented animals, HPA may be augmented (sensitization). The extent which this adaptation also evident within neural activity patterns unknown. This study tested whether repeated ferret odor (FO) exposure, psychological for rats, leads both same-stressor habituation and novel-stressor...
ABSTRACT Understanding the entry and trafficking mechanism(s) of recombinant adeno-associated virus (rAAV) into host cells can lead to evolution in capsid vector design delivery methods, resulting enhanced transduction therapeutic gene expression. Variability findings regarding early pathway rAAV supports possibility that rAAV, like other viruses, utilize more than one infectious pathway. We tested whether inhibition macropinocytosis impacted HeLa compared hepatocellular carcinoma cell...
Viruses depend upon the host cell for manufacturing components of progeny virions. To mitigate inextricable dependence on protein synthesis, viruses can modulate synthesis through a variety mechanisms. We report that viral kinase (vPK) encoded by open reading frame 36 (ORF36) Kaposi's sarcoma-associated herpesvirus (KSHV) enhances mimicking function cellular S6 (S6KB1). Similar to S6KB1, vPK phosphorylates ribosomal and up-regulates global synthesis. also augments proliferation...