A5086358405- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- DNA Repair Mechanisms
- Melanoma and MAPK Pathways
- Chemical Reactions and Isotopes
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Carcinogens and Genotoxicity Assessment
- Prostate Cancer Treatment and Research
- Lung Cancer Diagnosis and Treatment
- Cancer Cells and Metastasis
- Infection Control and Ventilation
- Computational Drug Discovery Methods
- Virus-based gene therapy research
- Neuroblastoma Research and Treatments
- Fibroblast Growth Factor Research
- PARP inhibition in cancer therapy
- Click Chemistry and Applications
- Immune cells in cancer
- BRCA gene mutations in cancer
University of Pennsylvania
2013-2025
QIMR Berghofer Medical Research Institute
2009-2023
The University of Queensland
1975-2023
Queensland University of Technology
2002-2020
Cancer Research Malaysia
2014-2019
Response Biomedical (Canada)
2009
Western University
1997
Mental Research Institute
1989-1995
Dermatology Research Center
1991
Lovelace Respiratory Research Institute
1990
The mammalian innate immune system is activated by foreign nucleic acids. Detection of double-stranded DNA (dsDNA) in the cytoplasm triggers characteristic antiviral responses and macrophage cell death. Cytoplasmic dsDNA rapidly caspase 3 1 bone marrow–derived macrophages. We identified HIN-200 family member candidate lupus susceptibility factor, p202, as a binding protein that bound stably to transfected DNA. Knockdown studies showed p202 be an inhibitor DNA-induced activation. Conversely,...
G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. genetically deregulated a variety tumor types can silence suppressor genes and, therefore, important for carcinogenesis. Although hypoxia recognized to be adverse factor growth metastasis, the role regulating expression has not been described extensively. Here, we show protein stability increased via reduced proline hydroxylation hence,...
Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived and RAW264 cell line. Overexpression a specific, alternatively spliced isoform lacking N-terminal 22 amino...
Histone deacetylases (HDACs) drive innate immune cell-mediated inflammation. Here we identify class IIa HDACs as key molecular links between Toll-like receptor (TLR)-inducible aerobic glycolysis and macrophage inflammatory responses. A proteomic screen identified the glycolytic enzyme pyruvate kinase M isoform 2 (Pkm2) a partner of proinflammatory Hdac7 in murine macrophages. Myeloid-specific overexpression transgenic mice amplifies lipopolysaccharide (LPS)-inducible lactate promotes...
Rationale: Epigenetic mechanisms are fundamental processes that can modulate gene expression, allowing cellular adaptation to environmental conditions. Hypoxia is an important factor known initiate the metastatic cascade in cancer, activating cell motility and invasion by silencing adhesion genes. G9a a histone methyltransferase previously shown accumulate hypoxic While its oncogenic activity has been reported, not much about role plays hypoxia-mediated cascade. Methods: The of condition was...
Abstract Purpose: G9a histone methyltransferase exerts oncogenic effects in several tumor types and its inhibition promotes anticancer effects. However, the impact on checkpoint inhibitor blockade response utility of or target genes as a biomarker is poorly studied. We aimed to examine whether can augment efficacy LC3B, gene, predict treatment response. Experimental Design: Clinical potential LC3B was assessed using patient samples including biopsies circulating cells from liquid biopsies....
Identification of germline mutations in DNA repair genes has significant implications for the personalized treatment individuals with prostate cancer (PrCa). To determine associated localized PrCa a diverse academic biobank and to genetic testing burden. A cross-sectional study 2391 patients was carried out. Genetic ancestry mutation rates (excluding somatic interference) 17 were determined 1588 3273 cancer-free males. Burden within genetically European (EUR) African (AFR) performed between...
Abstract TP53 is the most frequently mutated gene in cancer, and its encoded protein p53 has many tumor-suppressive functions. There are several different classes of mutant acquired human cancer inherited cancer-prone families with Li-Fraumeni Syndrome, where individuals have an 80-90% increased risk cancer. These include structural mutations that generally misfolded (R175H), DNA contact (R273H); oligomerization (A347D). A new class variants called “cooperativity” affect binding tetramer to...
Abstract IL-6 mediates broad physiological and pathological effects through its receptor signal transducing unit gp130. Due to the reportedly wide cellular expression of gp130, is thought ubiquitously via gp130 complex formation with membrane-bound IL-6Rα or soluble IL-6Rα. signaling primarily induces p-STAT3 p-STAT1. In contrast previous dogma, we show in this article that circulating mouse human granulocytes are unable induce p-STAT1 after stimulation an IL-6/soluble IL-6R complex....
Abstract G9a and EZH2 are two histone methyltransferases commonly upregulated in several cancer types, yet the precise roles that these enzymes play cooperatively is unclear. We demonstrate here frequent concurrent upregulation of both occurs human tumors. These repressed molecular pathways responsible for tumor cell death. In genetically distinct subtypes, concomitant inhibition potently induced death, highlighting existence survival dependency at epigenetic level. synergistically...
ABSTRACT Extended-spectrum β-lactamases (ESBLs) are active against oxyimino cephalosporins and monobactams. Twenty-one Klebsiella pneumoniae isolates obtained between 1991 1995 at the Princess Alexandra Hospital in Brisbane, Australia, were subject to amplification sequencing of SHV β-lactamase-encoding genes. Thirteen strains phenotypically ESBL positive. Of these, six carried bla SHV-2a gene seven SHV-12 gene. Eight negative. non-ESBL SHV-11 one strain SHV-1 There was complete...
Activation of the K-ras protooncogene and inactivation p53 tumor suppressor gene are events common to many types human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose this paper is review investigations that examined role lung tumors induced F344 rat by mutagenic nonmutagenic Mutation within genes, if present tumors, would help define some molecular mechanisms underlying cancer induction various environmental...
Abstract Specific, transforming point mutations of ras and alterations in expression have been associated with many neoplastic processes, their presence may be pivotal transformation. Our objectives were to evaluate the molecular genetic Ki‐ras preneoplastic foci neoplasms lungs rats that inhaled 239 PuO 2 aerosols. Histologically classified pulmonary lesions evaluated by vitro nucleic acid amplification, oligonucleotide hybridization, direct sequencing for activating mutations. We similar...
Production of the pigment eumelanin is controlled by α‐melanocyte stimulating hormone (α‐MSH) stimulation melanocortin 1 receptor (Mc1r), whereas production pheomelanin results from agouti antagonism α‐MSH signalling through Mc1r. The role in mouse pigmentation has been extensively investigated but a for protein (ASIP) human not determined. To determine whether ASIP regulates known melanogenic genes humans, was over‐expressed melanoma cell line. Levels mRNA and were measured to be up or...
Chemotherapy is used as a standard-of-care against cancers that display high levels of inherent genome instability. induces DNA damage and intensifies pressure on the repair pathways can lead to deregulation. There an urgent clinical need be able track emergence driven chemotherapy resistance tailor patient staging appropriately. have been numerous studies into chemoresistance but date no study has elucidated in detail roles key components associated with frontline combination anthracyclines...
The expression of epidermal growth factor receptor (EGF-R) was examined in canine lung tumors and proliferative epithelial foci induced by plutonium-239 to determine if EGF-R associated with specific neoplastic phenotypes or putative preneoplastic lesions. Seventeen (47%) 36 expressed EGF-R. Of these 17 tumors, three hybridized an erb-B RNA probe, which identified activated cell oncogenes. not correlated tumor etiology, e.g., spontaneous versus radiation induced, but did correlate histologic...
Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike cancer, anti-oestrogen therapy has had limited success in raising the possibility that different effects both cancers. We investigated role using data from The Cancer Genome Atlas (TCGA) conjunction with cell line studies. Using phosphorylation ERα (ERα-pSer118) as a marker transcriptional activation TCGA datasets, we found genes associated ERα-pSer118 were predominantly unique between tumour types...
overexpression of the erythroblast transformation‑specific‑related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)‑ERG fusion, most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared African or Asian descent. To best our knowledge, this first study investigate prevalence ERG alterations a multiethnic cohort CaP patients. A total 191 formalin‑fixed paraffin‑embedded sections transrectal...
10612 Background: Patients with Li-Fraumeni syndrome (LFS) are predisposed to a 90% lifetime risk of cancer, thus undergoing extensive cancer surveillance. While thyroid is not core LFS-associated malignancy, increased incidence carcinoma has been reported within the LFS tumor spectrum. In general population, soared mainly via incidental detection. We investigated rate in relation p53 mutational process and screening. Methods: A retrospective chart review was conducted for...
Tartrate-resistant acid phosphatases (TRAcPs), also known as purple (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is major histochemical marker for the diagnosis bone-related diseases. TRAcPs can occur small form possessing only ~35 kDa catalytic domain, or larger ~55 both domain an additional N-terminal unknown function. Due to its role bone resorption 35 TRAcP has become promising target development...
The tumor suppressor gene p53 plays a critical role in the cellular response to genetic damage caused by radiation. In addition, mutations this are often encountered cells lung tumors resected from uranium miners whose exposure radon daughters exceeded 450 working level months. However, most of these also smoked tobacco products. Thus whether is specific importance cancer unclear. study, aberrations were investigated using an immunohistochemical assay on 38 (26 squamous cell carcinomas, 9...
Membrane skeleton protein 4.1 and other members of a family proteins that link the cytoskeleton to plasma membrane may play an integral role in cell communication during development. The polymerase chain reaction degenerate oligodeoxynucleotide primers consensus sequences putative membrane-binding domain superfamily were used isolate cDNAs encoding zebrafish family. Zebrafish stage- tissue-specific first strand cDNA was PCR. After reaction, amplicons predicted size sequenced confirm their...
Abstract The adaptor protein ASC (apoptosis-associated speck-like containing a CARD) is known to facilitate caspase-1 activation, which essential for innate host immunity via the formation of inflammasome complex, multiprotein structure responsible processing IL1β and IL18 into their active moieties. Here, we demonstrated that ASC-deficient CD8+ T cells failed induce severe graft-versus-host disease (GVHD) had impaired capacity graft rejection graft-versus-leukemia (GVL) activity. These...