A5050309027- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- Circular RNAs in diseases
- Gut microbiota and health
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Acute Myeloid Leukemia Research
- Plant Molecular Biology Research
- T-cell and B-cell Immunology
- Plant nutrient uptake and metabolism
- Plant Virus Research Studies
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Reproductive System and Pregnancy
- Adipokines, Inflammation, and Metabolic Diseases
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
- Cancer-related molecular mechanisms research
- Autophagy in Disease and Therapy
- Retinoids in leukemia and cellular processes
- Clostridium difficile and Clostridium perfringens research
- Protein Degradation and Inhibitors
University of Utah
2017-2025
Huntsman Cancer Institute
2020-2025
Donald Danforth Plant Science Center
2018-2019
University of Missouri–St. Louis
2017
RAS mutations are among the most prevalent oncogenic drivers in cancers. proteins propagate signals only when associated with cellular membranes as a consequence of lipid modifications that impact their trafficking. Here, we discovered RAB27B, RAB family small GTPase, controlled NRAS palmitoylation and trafficking to plasma membrane, localization required for activation. Our proteomic studies revealed RAB27B upregulation CBL- or JAK2-mutated myeloid malignancies, its expression correlated...
Extracellular vesicles, including exosomes, have recently been implicated as novel mediators of immune cell communication in mammals. However, roles for endogenously produced exosomes regulating functions vivo are just beginning to be identified. In this article, we demonstrate that Rab27a and Rab27b double-knockout (Rab27DKO) mice deficient exosome secretion a chronic, low-grade inflammatory phenotype characterized by elevated cytokines myeloproliferation. Upon further investigation, found...
Identifying regulatory mechanisms that influence inflammation in metabolic tissues is critical for developing novel disease treatments. Here, we investigated the role of microRNA-146a (miR-146a) during diet-induced obesity mice. miR-146a reduced obese and type 2 diabetic patients our results reveal miR-146a-/- mice fed a high-fat diet (HFD) have exaggerated weight gain, increased adiposity, hepatosteatosis, dysregulated blood glucose levels compared to wild-type controls. Pro-inflammatory...
Abstract Tumor associated macrophage responses are regulated by distinct metabolic states that affect their function. However, the ability of specific signals in local tumor microenvironment to program metabolism remains under investigation. Here, we identify NAMPT, rate limiting enzyme NAD salvage synthesis, as a target STAT1 during cellular activation interferon gamma, an important driver polarization and antitumor responses. We demonstrate occupies conserved element within first intron...
Metabolic pathways regulate T cell development and function, but many remain understudied. Recently, the mitochondrial pyruvate carrier (MPC) was identified as transporter that mediates entry into mitochondria, promoting oxidation. Here we find deleting Mpc1, an obligate MPC subunit, in hematopoietic system results a specific reduction peripheral αβ numbers. MPC1-deficient cells have defective thymic at β-selection, intermediate single positive (ISP)-to-double-positive (DP), selection steps....
The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8+ T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific cell-expressed microRNAs. cell miR-155 is...
Intestinal epithelial cells (IECs) have long been understood to express high levels of major histocompatibility complex class II (MHC II) molecules but are not considered canonical antigen-presenting cells, and the impact IEC-MHC signaling on gut homeostasis remains enigmatic. As IECs serve as primary barrier between underlying host immune we reasoned that IEC-intrinsic antigen presentation may play a role in responses toward microbiota. Mice with an deletion MHC (IECΔMHC healthy fewer...
Abstract The proinflammatory microRNA-155 (miR-155) is highly expressed in the serum and CNS lesions of patients with multiple sclerosis (MS). Global knockout (KO) miR-155 mice confers resistance to a mouse model MS, experimental autoimmune encephalomyelitis (EAE), by reducing encephalogenic potential CNS-infiltrating Th17 T cells. However, cell-intrinsic roles for during EAE have not been formally determined. In this study, we use single-cell RNA sequencing cell-specific conditional KOs...
Abstract Aging-related chronic inflammation is a risk factor for many human disorders through incompletely understood mechanisms. Aged mice deficient in microRNA (miRNA/miR)-146a succumb to life-shortening inflammation. In this study, we report that miR-155 T cells contributes shortened lifespan of miR-146a−/− mice. Using single-cell RNA sequencing and flow cytometry, found promotes the activation effector cell populations, including follicular helper cells, increases germinal center B...
Intercellular communication is critical for homeostasis in mammalian systems, including the gastrointestinal (GI) tract. Exosomes are nanoscale lipid extracellular vesicles that mediate between many cell types. Notably, roles of immune exosomes regulating GI and inflammation largely uncharacterized. By generating mouse strains deficient cell-specific exosome production, we demonstrate deletion small GTPase Rab27A CD11c+ cells exacerbated murine colitis, which was reversible through...
Graphical Abstract We blocked pyruvate entry into mitochondria and decreased Oxidative Phosphorylation (OXPHOS) in human AML cell lines MV4-11 MOLM-14 by using gene editing tools. This metabolic shift led to increased expression of miR-1 the lines. TARGET TCGA patient sample dataset analysis revealed that is overexpressed patients with FLT3-ITD + mutation, independently from FLT3-ITD, high levels also correlates reduced survival. Transcriptional profiling overexpressing cells promotes OXPHOS...
ARGONAUTES are the central effector proteins of RNA silencing which bind target transcripts in a small RNA-guided manner. Arabidopsis thaliana has 10 ARGONAUTE (AGO) genes, with specialized roles RNA-directed DNA methylation, post-transcriptional gene silencing, and antiviral defense. To better understand specialization among AGO genes at level transcriptional regulation we tested library 1497 transcription factors for binding to promoters AGO1,AGO10, AGO7 using yeast 1-hybrid assays. A...
SUMMARY Regulation of the microbiota is critical to intestinal health yet mechanisms employed by innate immunity remain unclear. Here we show that mice deficient in C-Type-lectin receptor, Clec12a developed severe colitis, which was dependent on microbiota. Fecal-microbiota-transplantation (FMT) studies into germfree revealed a colitogenic formed within -/- marked expansion gram-positive organism, Faecalibaculum rodentium . Treatment with F. sufficient worsen colitis wild-type mice....
Abstract Colorectal cancer (CRC) is the 2 nddeadliest globally and has 3 rdhighest incidence mortality in United States. Advanced-stage disease incurable by current clinical standards. Thus, alternative treatments are being explored, including immune checkpoint blockade (ICB) to prevent T cell inactivation tumors. ICB induces a robust response patients with microsatellite instability-high (MSI-H) metastatic CRC. However, most CRC not responsive ICB. Our analysis revealed MSI-H exhibit an...
Endogenous small interfering (esi)RNAs repress mRNA levels and retrotransposon mobility in Drosophila somatic cells by poorly understood mechanisms. 21 nucleotide esiRNAs are primarily generated from retrotransposons two inverted repeat (hairpin) loci culture a Dicer2 dependent manner. Additionally, proteins involved 3' end processing, such as Symplekin, CPSF73 CPSR100, have been recently implicated the esiRNA pathway.Here we present evidence of overlap between essential RNA metabolic...
Abstract ARGONAUTES are the central effector proteins of RNA silencing which bind target transcripts in a small RNA-guided manner. Arabidopsis thaliana has ten ARGONAUTE (AGO) genes, with specialized roles RNA-directed DNA methylation, post-transcriptional gene silencing, and antiviral defense. To better understand specialization among AGO genes at level transcriptional regulation we tested library 1497 transcription factors for binding to promoters AGO1, AGO10 , AGO7 using yeast 1-hybrid...
Abstract Intercellular communication is critical for maintaining homeostasis in mammalian organ systems, including the gastrointestinal (GI) tract. Exosomes are small nanoscale lipid extracellular vesicles that mediate between a wide variety of cell types. Notably, roles played by immune exosomes regulating and inflammation GI tract largely uncharacterized. Here, we describe an unknown mechanism exosome-mediated regulation within By generating novel mouse strains, demonstrate disruption...