A5009131786- Cell death mechanisms and regulation
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- NF-κB Signaling Pathways
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- interferon and immune responses
- Lung Cancer Treatments and Mutations
- Immune Response and Inflammation
- Advanced Breast Cancer Therapies
- HER2/EGFR in Cancer Research
- Cancer therapeutics and mechanisms
- Immunotherapy and Immune Responses
- Hepatitis B Virus Studies
- Pleural and Pulmonary Diseases
- Biomedical and Engineering Education
- Protein Degradation and Inhibitors
- Cancer Treatment and Pharmacology
- Melanoma and MAPK Pathways
Walter and Eliza Hall Institute of Medical Research
2016-2025
Olivia Newton-John Cancer Wellness & Research Centre
2018-2025
La Trobe University
2018-2025
The University of Melbourne
2012-2025
Metropolitan University
2023
Sheba Medical Center
2023
Cancer Research Center
2018
Royal Women's Hospital
2013
The Royal Melbourne Hospital
2013
Inserm
2002-2011
The development of BH3 mimetics, which antagonize prosurvival proteins the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting member MCL-1 has been an area intense interest because it is frequently deregulated cancer. In breast cancer, often amplified, and high expression predicts poor patient outcome. We tested inhibitor S63845 cell lines patient-derived xenografts with MCL-1. displayed synergistic activity docetaxel triple-negative trastuzumab or lapatinib...
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that induces cancer cell death by apoptosis with some selectivity. TRAIL-induced mediated transmembrane receptors receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can also bind decoy 1 (DcR1) (TRAIL-R3) DcR2 (TRAIL-R4) fail to induce since they lack have truncated cytoplasmic domain, respectively. In addition, DcR1 inhibit DR4- DR5-mediated, we demonstrate here this occurs...
Proteins of the Bcl-2 family are critical regulators apoptosis, but how its BH3-only members activate essential effectors Bax and Bak remains controversial. The indirect activation model suggests that they simply must neutralize all prosurvival members, whereas direct proposes Bim Bid directly. As numerous in vitro studies have not resolved this issue, we investigated Bim's activity vivo by a genetic approach. Because BH3 domain determines binding specificity for relatives, generated mice...
Abstract Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) track the spatio-temporal fate thousands barcoded clones in primary tumors, their metastases. Tumor resection had a major impact on reducing clonal diversity secondary sites, indicating that most disseminated tumor cells lacked...
Human epidermal growth factor receptor-2 (HER2)-targeted therapies prolong survival in HER2-positive breast cancer patients. Benefit stems primarily from improved control of systemic disease, but up to 50% patients progress incurable brain metastases due acquired resistance and/or limited permeability inhibitors across the blood-brain barrier. Neratinib, a potent irreversible pan-tyrosine kinase inhibitor, prolongs disease-free extended adjuvant setting, and several trials evaluating its...
Background TRAIL/Apo2L is a pro-apoptotic ligand of the TNF family that engages apoptotic machinery through two receptors, TRAIL-R1 and TRAIL-R2. This cell death program tightly controlled by antagonistic TRAIL-R3 TRAIL-R4, both devoid functional domain, an intracellular region receptor, required for recruitment activation initiator caspases. Upon TRAIL-binding, TRAIL-R4 forms heteromeric complex with agonistic receptor TRAIL-R2 leading to reduced caspase-8 apoptosis. Methodology/Principal...
Abstract Smac mimetics target inhibitor of apoptosis (IAP) proteins, thereby suppressing their function to facilitate tumor cell death. Here we have evaluated the efficacy preclinical Smac-mimetic compound A and clinical lead birinapant on breast cancer cells. Both exhibited potent in vitro activity triple-negative (TNBC) cells, including those from patient-derived xenograft (PDX) models. Birinapant was further studied using vivo PDX models TNBC estrogen receptor-positive (ER + ) cancer....
Solid tumours routinely access the blood supply by promoting endothelium-dependent angiogenesis; but tumour vasculature can also be formed cancer cells themselves via vasculogenic mimicry (VM). Investigation of gene expression profile during early stages VM formation MDA-MB-231-LM2 breast identified transcriptional regulator inhibitor DNA binding 1 (ID1) to elevated ~ 10-fold within first 2 hours. This role for ID1 in was supported genetic knockdown or chemical inhibition interrupting...
Arsenic trioxide (As<sub>2</sub>O<sub>3</sub>) is known to be toxic toward leukemia cells. In this study, we determined its effects on survival of human monocytic cells during macrophagic differentiation, an important biological process involved in the immune response. As<sub>2</sub>O<sub>3</sub> used at clinically relevant pharmacological concentrations induced marked apoptosis blood monocytes differentiation with either granulocyte-macrophage colony-stimulating factor or macrophage factor....
Abstract Tumor necrosis factor-α–related apoptosis-inducing ligand (TRAIL) is a potential anticancer agent that induces apoptosis in cancer cells but not most normal cells. How tumor physiology, particularly acidic extracellular pH (pHe), would modify sensitivity of to TRAIL-induced cell death known. We have previously shown cells, resistant at physiologic pHe (7.4), could be sensitized TRAIL (6.5). However, this pHe, was necrotic. show here that, spite necrosis-like morphology, caspases are...
Intratumoral heterogeneity is a driver of breast cancer progression, but the nature clonal interactive network involved in this process remains unclear. Here, we optimized use optical barcoding to visualize and characterize 31 subclones vivo. By mapping composition thousands metastases two clinically relevant sites, lungs liver, found that were highly polyclonal not liver. Furthermore, transcriptome varied according their metastatic niche. We also identified reversible niche-driven signature...