A5103151515- Cell death mechanisms and regulation
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Cytokine Signaling Pathways and Interactions
- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- interferon and immune responses
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Molecular Biology Techniques and Applications
- Sleep and Wakefulness Research
- Diabetes Management and Research
- X-ray Diffraction in Crystallography
- Cancer Mechanisms and Therapy
- CAR-T cell therapy research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Signaling Pathways in Disease
- Cancer therapeutics and mechanisms
- RNA modifications and cancer
- Plant Molecular Biology Research
- Phagocytosis and Immune Regulation
- Gene expression and cancer classification
North-West University
2024
University of California, Santa Cruz
2022-2023
Walter and Eliza Hall Institute of Medical Research
2012-2021
The University of Melbourne
2012-2020
University of California, Davis
2015
Deakin University
2002-2010
Nutrition Sciences (Belgium)
2006
Rockland Community College
2006
RELX Group (United States)
2005
National Institutes of Health
1998-2004
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...
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...
Improving outcomes in acute myeloid leukemia (AML) remains a major clinical challenge. Overexpression of pro-survival BCL-2 family members rendering transformed cells resistant to cytotoxic drugs is common theme cancer. Targeting with the BH3-mimetic venetoclax active AML when combined low-dose chemotherapy or hypomethylating agents. We now report pre-clinical anti-leukemic efficacy novel inhibitor S55746, which demonstrates synergistic pro-apoptotic activity combination MCL1 S63845....
PERIOD (PER) and Casein Kinase 1δ regulate circadian rhythms through a phosphoswitch that controls PER stability repressive activity in the molecular clock. CK1δ phosphorylation of familial advanced sleep phase (FASP) serine cluster embedded within 1 binding domain (CK1BD) mammalian PER1/2 inhibits its on phosphodegrons to stabilize extend period. Here, we show phosphorylated FASP region (pFASP) PER2 directly interacts with CK1δ. Co-crystal structures conjunction dynamics simulations reveal...
Mice with a null mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop disease marked expansion granulocytes and macrophages that frequently progresses to fatal blast crisis, thus resembling human chronic myelogenous leukemia (CML). One important feature CML is decreased responsiveness myeloid cells apoptotic stimuli. Here we show from mice deficient in ICSBP exhibit reduced spontaneous apoptosis significant decrease sensitivity induced by DNA damage. In...
Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies several infectious, allergic, autoimmune diseases have shown that chronic type-1 type-2 cytokine can also cause significant morbidity mortality if left unchecked. We used mouse cDNA microarrays molecularly phenotype the gene expression patterns characterize two disparate but equally lethal forms liver pathology develop in Schistosoma mansoni infected mice for responses....
Skeletal muscle tissue undergoes adaptive changes in response to stress and the genes that control these processes are incompletely characterised. NDRG2 (N-myc downstream-regulated gene 2), a stress- growth-related gene, was investigated skeletal growth adaption. While expression levels were found be up-regulated both differentiated human mouse myotubes compared with undifferentiated myoblasts, suppression of C2C12 myoblasts resulted slowed myoblast proliferation. The increased cell cycle...
A number of diazepines are known to inhibit bromo- and extra-terminal domain (BET) proteins. Their BET inhibitory activity derives from the fusion an acetyl-lysine mimetic heterocycle onto diazepine framework. Herein we describe a straightforward, modular synthesis novel 1,2,3-triazolobenzodiazepines show that 1,2,3-triazole acts as effective heterocycle. Structure-based optimization this series compounds led development potent bromodomain inhibitors with excellent against leukemic cells,...