A5013835204- Helicobacter pylori-related gastroenterology studies
- Mycobacterium research and diagnosis
- Veterinary medicine and infectious diseases
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Sphingolipid Metabolism and Signaling
- Microscopic Colitis
- Histone Deacetylase Inhibitors Research
- Colorectal Cancer Screening and Detection
- Cancer-related molecular mechanisms research
- Protein Kinase Regulation and GTPase Signaling
- Esophageal Cancer Research and Treatment
- Colorectal Cancer Treatments and Studies
- PI3K/AKT/mTOR signaling in cancer
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomic variations and chromosomal abnormalities
- Mechanisms of cancer metastasis
- Single-cell and spatial transcriptomics
- Neuroblastoma Research and Treatments
- Vitamin D Research Studies
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- Pain Mechanisms and Treatments
University of Virginia
2020-2025
University of Helsinki
2024
University of Luxembourg
2023
Maastricht University
2023
Office of Public Health Genomics
2020-2023
University of Georgia
2010-2018
Georgia College & State University
2018
University of Hawaii at Hilo
2017
Georgia State University
2016
RGS10 is an important regulator of cell survival and chemoresistance in ovarian cancer. We recently showed that transcript expression suppressed during acquired The suppression due to DNA hypermethylation histone deacetylation, two mechanisms contribute silencing tumor suppressor genes cancer progression. Here, we fully investigate the molecular epigenetic chemoresistant A2780-AD cells. identify regulators, HDAC1 DNMT1, exhibit aberrant association with promoters Knockdown or DNMT1...
A critical therapeutic challenge in epithelial ovarian carcinoma is the development of chemoresistance among tumor cells following exposure to first line chemotherapeutics. The molecular and genetic changes that drive are unknown, this lack mechanistic insight a major obstacle preventing predicting occurrence refractory disease. We have recently shown Regulators G-protein Signaling (RGS) proteins negatively regulate signaling by lysophosphatidic acid (LPA), growth factor elevated malignant...
Abstract Patients receiving paclitaxel for cancer treatment often develop an acute pain syndrome (paclitaxel‐associated syndrome, P‐APS), which occurs immediately after treatment. Mechanisms underlying P‐APS remain largely unknown. We recently reported that rodents and activation of spinal microglial toll like receptor 4 (TLR4) by penetrating into the cord is a critical event in genesis P‐APS. Our current study dissected cellular molecular mechanisms demonstrated bath‐perfusion paclitaxel,...
RGS10 regulates ovarian cancer cell growth and survival, expression is suppressed in models of chemoresistance. However, the mechanisms governing are poorly understood. Here we report suppression primary CAOV-3 cells compared to immortalized surface epithelial (IOSE) cells, A2780-AD chemoresistant parental A2780 cells. RGS10-1 RGS10-2 transcripts expressed but only promoter uniquely enriched CpG dinucleotides. Pharmacological inhibition DNA methyl-transferases (DNMTs) increased expression,...
RGS10 has emerged as a key regulator of proinflammatory cytokine production in microglia, functioning an important neuroprotective factor. Although is normally expressed microglia at high levels, expression silenced vitro following activation TLR4 receptor. Given the ability to regulate inflammatory signaling, dynamic regulation levels may be mechanism tune responses. The goals current study were confirm that suppressed vivo model microglial and determine for activation-dependent silencing...
Abstract Background Familial adenomatous polyposis (FAP) is an inherited colorectal cancer (CRC) syndrome resulting from germ line mutations in the coli ( APC ) gene. While FAP accounts for less than 1% of all CRC cases, loss expression seen > 80% non-hereditary CRCs. To better understand molecular mechanisms underlying APC-driven CRC, we performed epigenome-wide analysis colon organoids derived normal-appearing colons patients versus healthy subjects to identify differentially methylated...
Abstract Introduction Lynch syndrome (LS) is a hereditary condition that increases the risk of colorectal (CRC) and extracolonic cancers exhibit microsatellite instability (MSI‐H). MSI‐H driven by defective mismatch repair (dMMR), approximately 15% nonhereditary CRCs also MSI‐H. Here, we aimed to better define mechanisms underlying tumor initiation in LS through multi‐omic analyses normal colon organoids tumors. Methods Right ( n = 35) left 23) generated from biopsies at routine colonoscopy...
We present an efficient approach for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to rapidly create a library of complex functional ionizable lipopolymers. synthesized diverse 155 polymers, formulated them into polyplexes establish structure-activity relationships crucial endosomal escape and transfection. After discovering lead structure, lipopolymer-lipid hybrid nanoparticles are introduced preferentially deliver elicit effective mRNA...
G protein-coupled receptors (GPCRs) and their ligands are critical regulators of neural progenitor differentiation, GPCR signaling pathways regulated by regulator protein (RGS) proteins. RGS expression is dynamically regulated, we have recently described the epigenetic regulation transcript expression. Given potential proteins to regulate established role in explored impact transcripts during vitro differentiation human progenitors. Here, demonstrate robust upregulation RGS4, RGS5, RGS6,...
// Ingo Lange 1 , Italo Espinoza-Fuenzalida Mourad Wagdy Ali Laura Espana Serrano and Dana-Lynn T. Koomoa University of Hawaii at Hilo, The Daniel K. Inouye College Pharmacy, HI 96720, USA Correspondence to: Koomoa, email: danalynn@hawaii.edu Lange, ingo@hawaii.edu Keywords: neuroblastoma; calcium; FTY720; TRPM7; channel Received: June 08, 2017 Accepted: October 17, Published: November 06, ABSTRACT Neuroblastoma (NB) is the most common extra-cranial pediatric solid tumor. High-risk NB...
The bioactive lysophospholipids lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) have diverse effects on the developing nervous system neural progenitors, but molecular basis for their pleiotropic is poorly understood. We previously defined LPA S1P signaling in proliferating human progenitor (hNP) cells, current study investigates role neuronal differentiation of these cells. Differentiation presence or significantly enhanced cell survival decreased expression markers. Further,...
Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with glioma risk on 20q13.33, but the biological mechanisms underlying this are unknown. We tested hypothesis that a functional SNP 20q13.33 impacted activity of an enhancer, leading to altered expression nearby genes. To identify candidate SNPs, we all SNPs in linkage disequilibrium risk-associated rs2297440 mapped putative enhancers. Putative enhancers containing were for...
Abstract Mechanisms underlying aspirin chemoprevention of colorectal cancer remain unclear. Prior studies have been limited because the inability preclinical models to recapitulate human normal colon epithelium or cellular heterogeneity present in mucosal biopsies. To overcome some these obstacles, we performed vitro treatment organoids derived from biopsies reveal transcriptional networks relevant chemoprevention. Colon 38 healthy individuals undergoing endoscopy were treated with 50 μmol/L...
Several genome wide association studies of colorectal cancer (CRC) have identified single nucleotide polymorphisms (SNPs) on chromosome 15q13.3 associated with CRC risk. To identify functional variant(s) underlying this association, we investigated SNPs in linkage disequilibrium the risk-associated SNP rs4779584 that overlapped regulatory regions/enhancer elements characterized colon-related tissues and cells. We several SNP-containing regions exhibited enhancer activity vitro, including one...
Genome-wide association studies have identified SNPs associated with glioma risk on 9p21.3, but biological mechanisms underlying this are unknown. We tested the hypothesis that a functional SNP 9p21.3 affects activity of an enhancer, causing altered expression nearby genes. considered all in linkage disequilibrium sentinel rs634537 mapped to putative enhancers. An enhancer containing rs1537372 exhibited allele-specific effects luciferase activity. Deletion GBM cell lines correlated decreased...
Tobacco smoke and red/processed meats are well-known risk factors for colorectal cancer (CRC). Most research has focused on studies of normal colon biopsies in epidemiologic or treatment CRC cell lines vitro. These often constrained by challenges with accuracy self-report data or, the case lines, small sample sizes lack relationship to tissue at risk. In an attempt address some these limitations, we performed a 24-hour representative carcinogens cocktail 37 independent organoid derived from...
Abstract Observational studies indicate that calcium supplementation may protect against colorectal cancer. Stratified analyses suggest this protective effect differ based on anatomic subsite and sex, but these hypotheses have been difficult to test experimentally. Here, we exposed 36 patient-derived organoid lines derived from normal colon biopsies (21 right colons, 15 left colons) of unrelated subjects (18 female, 18 male) moderate (1.66 mmol/L) or high (5.0 concentrations for 72 hours. We...
Genome-wide association studies (GWAS) have identified ~20 genetic susceptibility loci for esophageal adenocarcinoma (EAC), and its precursor, Barrett's esophagus (BE). Despite such advances, functional/causal variants gene targets at these remain undefined, hindering clinical translation. A key challenge is that most causal map to non-coding regulatory regions as enhancers, typically, numerous potential candidate GWAS require testing. We developed a systematic informatics pipeline...
Abstract Nineteen genetic susceptibility loci for esophageal adenocarcinoma (EAC) and its precursor Barrett’s esophagus (BE) have been identified through genome-wide association studies (GWAS). Clinical translation of such discoveries, however, has hindered by the slow pace discovery functional/causal variants gene targets at these loci. We previously developed a systematic informatics pipeline to prioritize candidate functional using potential scores, applied select high-scoring BE/EAC risk...
Early onset colorectal cancer (EOCRC) rates have increased in recent decades. While lowering the recommended age for routine colonoscopies to 45 may reduce this burden, such measures do not address those who develop CRC before that age. Additional are needed identify individuals at-risk CRC. To better define transcriptomic events precede development of CRC, we performed RNA-sequencing analysis colon organoids derived from seven healthy and six familial adenomatous polyposis (FAP) patients....
The development of chemoresistance represents a critical therapeutic challenge in epithelial ovarian carcinoma. Receptor‐stimulated survival pathways are amplified chemoresistant cells. RGS proteins suppress GPCR stimulated signaling. We have recently reported RGS2, 10, and 17 downregulated models acquired cancer. Further, transcript expression is decreased following short term exposure to chemotherapeutic drugs. This suggests model which reduced drugs, thus indirectly amplifying mediated...
Regulator of G‐protein Signaling 10 (RGS10) has emerged as a key regulator pro‐inflammatory cytokine production in microglia, functioning an important neuroprotective factor. While RGS10 is normally expressed microglia at high levels, expression silenced vitro following activation TLR4 receptor‐activation. Given the ability to regulate inflammatory signaling, dynamic regulation may be mechanism tune responses. The goals current study were confirm that vivo model microglial and determine for...