A5023652153- Wnt/β-catenin signaling in development and cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer-related gene regulation
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Helicobacter pylori-related gastroenterology studies
- interferon and immune responses
- Gut microbiota and health
- Chemokine receptors and signaling
- Eicosanoids and Hypertension Pharmacology
- Cancer Research and Treatments
- Inflammasome and immune disorders
- Heart Rate Variability and Autonomic Control
- Genetic factors in colorectal cancer
- PARP inhibition in cancer therapy
- IL-33, ST2, and ILC Pathways
- RNA Research and Splicing
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Spaceflight effects on biology
- Inflammatory Bowel Disease
- Pancreatic and Hepatic Oncology Research
- Neuroblastoma Research and Treatments
- Immunotherapy and Immune Responses
University of Colorado Anschutz Medical Campus
2020-2023
University of Colorado Denver
2020-2023
Michigan State University
2018-2019
Grand Valley State University
2018-2019
Abstract Background Intestinal epithelial cell (IEC) mitochondrial dysfunction involvement in inflammatory bowel diseases (IBD), including Crohn’s disease affecting the small intestine, is emerging recent studies. As interface between self and gut microbiota, IECs serve as hubs of bidirectional cross-talk host luminal microbiota. However, role mitochondrial-microbiota interaction ileum largely unexplored. Prohibitin 1 (PHB1), a chaperone protein inner membrane required for optimal electron...
Paneth cell defects in Crohn’s disease (CD) patients (called the Type I phenotype) are associated with worse clinical outcomes. Recent studies have implicated mitochondrial dysfunction cells as a mediator of ileitis mice. We hypothesized that CD exhibit impaired health and mitochondrial-targeted therapeutics may provide novel strategy for ileal CD. Terminal mucosal biopsies from adult non-IBD were characterized phenotyping damage. To demonstrate response CD, treated vehicle or Mito-Tempo,...
Colorectal cancer exhibits aberrant activation of Wnt/β-catenin signaling. Many inhibitors the pathway have been tested for Wnt-dependent cancers including colorectal cancer, but are unsuccessful due to severe adverse reactions. FL3 is a synthetic derivative natural products called flavaglines, which exhibit anti-inflammatory and cytoprotective properties in intestinal epithelial cells, has not previously cell or preclinical models tumorigenesis. In vitro studies suggest that flavaglines...
Autophagy of damaged mitochondria, called mitophagy, is an important organelle quality control process involved in the pathogenesis inflammation, cancer, aging, and age-associated diseases. Many these disorders are associated with altered expression inner mitochondrial membrane (IMM) protein Prohibitin 1. The mechanisms whereby dysfunction occurring internally at IMM matrix activate events outer (OMM) to induce mitophagy not fully elucidated. Using gastrointestinal epithelium as a model...
Defining feature of pancreatic ductal adenocarcinoma (PDAC) that participates in the high mortality rate and drug resistance is immune-tolerant microenvironment which enables tumors to progress unabated by adaptive immunity. In this study, we report PDAC cells release CSF-1 induce nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) activation myeloid cells. Increased NLRP3 expression was found pancreas patients with when compared normal correlated...
The heat shock response is a critical component of the inflammatory cascade that prevents misfolding new proteins and regulates immune responses. Activation clusters differentiation (CD)4+ T cells causes an upregulation transcription factor, factor 1 (HSF1). We hypothesized HSF1 promotes pro-regulatory phenotype during inflammation. To validate this hypothesis, we interrogated cell-specific knockout mice transgenic using in vitro vivo techniques. determined while expression was induced by...
Abstract The mammogenic, lactogenic, and lactopoetic effects of prolactin (PRL) in the mammary gland are mediated through a specific cytokine receptor, PRL-receptor (PRLR). PRLR is anchored to cytoskeleton its activation, subsequent signal transduction, dependent on an integral/intact cytoskeletal organization. Previous studies revealed down-regulation reduced metabolic output rats exposed hypergravity (HG). Therefore, objective this study was use quantitative immunohistochemistry determine...
Dysbiosis in gut microbiota is associated with inflammatory bowel diseases (IBD), such as Crohn's disease. Prohibitin 1 (PHB1) a mitochondrial protein important optimal respiration and decreased biopsies from IBD patients. Intestinal epithelial dysfunction emerging an underlying contributor to inflammation IBD. Previous studies our laboratory have demonstrated that mice Phb1-deficiency the intestinal epithelium (Phb1iΔIEC ) manifest dysfunction, Paneth cell defects, spontaneous ileum...
Abstract INTRODUCTION Prohibitin 1 (PHB1) is a mitochondrial chaperone protein important for maximal activity of the electron transport chain. PHB1 deficiency in intestinal epithelial cells (IECs) or specifically Paneth (PCs) induces dysfunction, PC defects, gut microbiota dysbiosis, and spontaneous ileitis mice by 20 weeks-of-age. Dysbiotic has been implicated inflammatory bowel diseases associated with decreased abundance short chain fatty acids (SCFAs; acetate, propionate,...
<div>Abstract<p>Colorectal cancer exhibits aberrant activation of Wnt/β-catenin signaling. Many inhibitors the pathway have been tested for Wnt-dependent cancers including colorectal cancer, but are unsuccessful due to severe adverse reactions. FL3 is a synthetic derivative natural products called flavaglines, which exhibit anti-inflammatory and cytoprotective properties in intestinal epithelial cells, has not previously cell or preclinical models tumorigenesis. <i>In...
<div>Abstract<p>Colorectal cancer exhibits aberrant activation of Wnt/β-catenin signaling. Many inhibitors the pathway have been tested for Wnt-dependent cancers including colorectal cancer, but are unsuccessful due to severe adverse reactions. FL3 is a synthetic derivative natural products called flavaglines, which exhibit anti-inflammatory and cytoprotective properties in intestinal epithelial cells, has not previously cell or preclinical models tumorigenesis. <i>In...
<p>PHB1 expression is required for FL3 anti-tumorigenic action in the colon</p>
<p>Supplemental methods</p>
<p>Inhibition of Wnt/β-catenin by FL3 is prevented S45 deletion</p>
<p>FL3 does not decrease viability in IEC6 cells compared to standard CRC chemotherapeutic drugs.</p>
<p>In vivo cell proliferation and GI histology are not altered by FL3</p>
<p>FL3 induces death of established colonic tumoroids derived from mice.</p>
<p>FL3 does not alter cell proliferation</p>
<p>FL3 induces RKO and SW48 cell death</p>
<p>Inhibition of Wnt/β-catenin by FL3 is prevented S45 deletion</p>
<p>FL3 does not alter cell proliferation</p>