A5056928011- Histone Deacetylase Inhibitors Research
- Autophagy in Disease and Therapy
- PARP inhibition in cancer therapy
- Cancer Mechanisms and Therapy
- Advanced Breast Cancer Therapies
- Melanoma and MAPK Pathways
- Cell death mechanisms and regulation
- Lipid metabolism and disorders
- Cancer Treatment and Pharmacology
- Cancer, Stress, Anesthesia, and Immune Response
- Ferroptosis and cancer prognosis
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Extracellular vesicles in disease
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Biomedical Research and Pathophysiology
- FOXO transcription factor regulation
- Bacillus and Francisella bacterial research
- Kruppel-like factors research
- Apelin-related biomedical research
- Phagocytosis and Immune Regulation
- Lysosomal Storage Disorders Research
- Nanopore and Nanochannel Transport Studies
- Helicobacter pylori-related gastroenterology studies
Olivia Newton-John Cancer Wellness & Research Centre
2019-2025
La Trobe University
2019-2025
Peter MacCallum Cancer Centre
2017
Keck Graduate Institute
2016
Abstract Malignant melanoma is one of the most difficult cancers to treat due its resistance chemotherapy. Despite recent successes with BRAF inhibitors and immune checkpoint inhibitors, many patients do not respond or become resistant these drugs. Hence, alternative treatments are still required. Due importance BCL-2-regulated apoptosis pathway in cancer development drug resistance, it interest establish which proteins important for cell survival, though outcomes previous studies have been...
Autophagy-related genes have been closely associated with intestinal homeostasis. BECLIN1 is a component of Class III phosphatidylinositol 3-kinase complexes that orchestrate autophagy initiation and endocytic trafficking. Here we show epithelium-specific deletion in adult mice leads to rapid fatal enteritis compromised gut barrier integrity, highlighting its intrinsic critical role maintenance. BECLIN1-deficient epithelial cells exhibit extensive apoptosis, impaired autophagy, stressed...
BECN1/Beclin 1 is a critical protein in the initiation of autophagosome formation. Recent studies have shown that phosphorylation BECN1 by STK4/MST1 at threonine 108 (T108) within its BH3 domain blocks macroautophagy/autophagy increasing affinity for negative regulators, anti-apoptotic proteins BCL2/Bcl-2 and BCL2L1/Bcl-xL. It was proposed this increased binding due to formation an electrostatic interaction with conserved histidine residue on molecules. Here, we performed biophysical which...
Disrupted intestinal homeostasis and barrier function contribute to the development of diseases such as inflammatory bowel disease. BECLIN-1, a core component two class III phosphatidylinositol 3 kinase complexes, has dual role in autophagy endocytic trafficking. Emerging evidence suggests that its trafficking is essential for integrity. To investigate fatal gastrointestinal phenotype observed BECLIN-1 knockout mice, we used organoids derived from these animals show deletion disrupts...
The prototypical autophagy regulator BECLIN1, orchestrates both autophagic and endocytic trafficking, its homozygous deletion in the intestinal epithelium leads to disruption bearing similarities inflammatory bowel disease (IBD). However, complete loss of BECLIN1 is rare human disease. To model effects a partial reduction we examined mice with monoallelic Becn1 epithelium, which decreased protein levels by approximately 50%. Unlike fatal phenotype following deletion, heterozygous were...
Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach discovering therapies capable of inhibiting that mediate multiple pathways. This can be widely used, as it combines genetic-based target identification with cell survival-based protein function-based multiplex drug screens, concurrently discovers therapeutic compounds their targets....
Landmark genome-wide association studies (GWAS) identified that mutations in autophagy genes correlated with inflammatory bowel disease (IBD), a heterogenous characterised by prolonged inflammation of the gastrointestinal tract, can reduce person's quality life. Autophagy, delivery intracellular components to lysosome for degradation, is critical cellular housekeeping process removes damaged proteins and turns over organelles, recycling their amino acids other constituents supply cells...
Abstract The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors this that they primarily induce cytostatic effects cancer cells. Nevertheless, these drugs do expression proapoptotic factors, suggesting may prime cells to undergo apoptosis. As histone deacetylase (HDACis) multiple proteins, we examined whether could synergize with ERK/MAPK trigger cell Combined MEK/ERK and HDAC inhibition synergistically induced...
Abstract The major limitations of pathogen-directed therapies are the emergence drug-resistance and their narrow spectrum coverage. A recently applied approach directs against host proteins exploited by pathogens in order to circumvent these limitations. However, host-oriented drugs leave unaffected may result continued pathogen dissemination. In this study we aimed discover that could simultaneously cross-inhibit pathogenic agents, as well mediate lethality. We observed many host-assisting...
Abstract Early studies of the free-living nematode C. elegans informed us how BCL-2-regulated apoptosis in humans is regulated. However, subsequent showed has several unique features compared with human apoptosis. To date, there been no detailed analysis regulators nematodes other than . Here, we discovered BCL-2 orthologues 89 and parasitic taxa representing four evolutionary clades (I, III, IV V). Unlike , 15 species possess multiple (two to five) BCL-2-like proteins, some do not have any...
Abstract Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial constantly exposed to a variety molecular factors and shear force that can induce cellular damage stress. However, how removed or eliminate unwanted contents, remains unclear. The generation large extracellular vesicles (EVs) has emerged as key mechanism for removal waste from dying stressed. Here, we used intravital microscopy bone marrow directly...
ABSTRACT Disrupted intestinal homeostasis and barrier function are key contributors to the development of various diseases, including inflammatory bowel disease (IBD). BECLIN-1, a core component two class III phosphatidylinositol 3-kinase (PtdIns3K) complexes, has dual role in autophagy endocytic trafficking. Emerging evidence suggests it is involved maintaining integrity which involves its trafficking function. To gain insights into fatal gastrointestinal (GI) phenotype observed BECLIN-1...
<p>Supplementary figure 2 shows the effect of trametinib plus panobinostat on colony formation in HCT 116 cells</p>
<p>Supplementary figure 3 shows combining trametinib with different classes of HDAC inhibitors in COLO 201 cells</p>
<div>Abstract<p>The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors this that they primarily induce cytostatic effects cancer cells. Nevertheless, these drugs do expression proapoptotic factors, suggesting may prime cells to undergo apoptosis. As histone deacetylase (HDACis) multiple proteins, we examined whether could synergize with ERK/MAPK trigger cell Combined MEK/ERK and HDAC inhibition...
<p>Supplementary Figure 1 shows the synergistic effect of trametinib plus panobinostat in CRC cell lines and PDTO's</p>
<p>Supplementary figure 2 shows the effect of trametinib plus panobinostat on colony formation in HCT 116 cells</p>
<p>Supplementary figure 3 shows combining trametinib with different classes of HDAC inhibitors in COLO 201 cells</p>
<div>Abstract<p>The EGFR/RAS/MEK/ERK signaling pathway (ERK/MAPK) is hyperactivated in most colorectal cancers. A current limitation of inhibitors this that they primarily induce cytostatic effects cancer cells. Nevertheless, these drugs do expression proapoptotic factors, suggesting may prime cells to undergo apoptosis. As histone deacetylase (HDACis) multiple proteins, we examined whether could synergize with ERK/MAPK trigger cell Combined MEK/ERK and HDAC inhibition...
<p>Supplementary figure 4 shows phosphorylated ERK staining in an adenoma from a ACDX2 mouse</p>