A5060118604- Cellular transport and secretion
- PI3K/AKT/mTOR signaling in cancer
- Wnt/β-catenin signaling in development and cancer
- Protein Kinase Regulation and GTPase Signaling
- Autophagy in Disease and Therapy
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Calcium signaling and nucleotide metabolism
- Retinal Development and Disorders
- Cannabis and Cannabinoid Research
- Cell Adhesion Molecules Research
- Renal and related cancers
- Toxoplasma gondii Research Studies
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Lipid Membrane Structure and Behavior
- Peptidase Inhibition and Analysis
Australian Regenerative Medicine Institute
2019-2023
Monash University
2017-2023
Abstract INPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P 2 to PI(3)P and inactivation is common in triple-negative breast cancer. Paradoxically, also a reported oncogene other cancers. How these opposing roles relate PI3K regulation unclear. We report PIK3CA -mutant ER + cancers exhibit increased mRNA protein expression the proliferation tumor growth of cancer cells, despite suppression AKT signaling. used integrated proteomics, transcriptomics imaging demonstrate localized late...
Abstract Autophagy depends on the repopulation of lysosomes to degrade intracellular components and recycle nutrients. How cells co‐ordinate lysosome during basal autophagy, which occurs constitutively under nutrient‐rich conditions, is unknown. Here, we identify an endosome‐dependent phosphoinositide pathway that links PI3Kα signaling autophagy. We show PI3Kα‐derived PI(3)P generated by INPP4B late endosomes was required for but not starvation‐induced autophagic degradation. signals were...
Abstract Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal involves a phosphoinositide-driven gain or loss proteins on individual endosomes, emphasising an autonomous stochastic description. However, limitations in fast, volumetric imaging long hindered direct whole cell-level measurements absolute numbers events. Here, we use lattice light-sheet bespoke automated analysis track very...
Despite significant progress, our understanding of how specific oncogenes transform cells is still limited and likely underestimates the complexity downstream signalling events. To address this gap, we use mass spectrometry-based chemical proteomics to characterize global impact an oncogene on expressed kinome, then functionally annotate regulated kinases. As example, identify 63 protein kinases exhibiting altered expression and/or phosphorylation in Src-transformed mammary epithelial cells....
The majority of breast cancers are estrogen receptor-positive (ER+), and endocrine therapies that suppress ER signaling the standard-of-care treatment for this subset. However, up to half all ER+ eventually relapse, highlighting a need improved clinical therapies. phosphoinositide phosphatase, INPP4B, is overexpressed in almost cancers, promotes Wnt/β-catenin signaling, cell proliferation tumor growth. Here, using viability assays, we report INPP4B overexpression does not affect sensitivity...
Macroautophagy/autophagy occurs basally under nutrient-rich conditions in most mammalian cells, contributing to protein and organelle quality control, protection against aging neurodegeneration. During autophagy, lysosomes are heavily utilized via their fusion with autophagosomes must be repopulated maintain autophagic degradative capacity. starvation-induced generated de novo biogenesis the control of TFEB (transcription factor EB), or by recycling autolysosome membranes lysosome...
AKT is the central phosphoinositide 3-kinase (PI3K) signaling effector, however, PIK3CA (p110α subunit of PI3Kα)-mutant estrogen receptor-positive (ER+) breast cancers exhibit minimal activation and downstream poorly characterized. We discovered that a subset PIK3CA-mutant ER+ increased inositol polyphosphate 4-phosphatase type II (INPP4B) expression, which promotes late endosome formation glycogen synthase kinase 3 beta (GSK3β) trafficking, leading to enhanced Wingless-related integration...