A5067011297- Neurogenesis and neuroplasticity mechanisms
- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- Advanced Neuroimaging Techniques and Applications
- Neuroblastoma Research and Treatments
- Neonatal Respiratory Health Research
- RNA Interference and Gene Delivery
- Advanced MRI Techniques and Applications
- Protein Degradation and Inhibitors
- Alzheimer's disease research and treatments
- Garlic and Onion Studies
- Immune cells in cancer
- Functional Brain Connectivity Studies
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Microtubule and mitosis dynamics
- Ocular Oncology and Treatments
- Mesenchymal stem cell research
- Brain Metastases and Treatment
- Cancer Mechanisms and Therapy
Stanford University
2023-2024
Australian Regenerative Medicine Institute
2021-2024
Monash University
2021-2024
Fudan University
2024
Palo Alto University
2023
Florey Institute of Neuroscience and Mental Health
2014-2018
The University of Melbourne
2012-2018
Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which is capable regulating myelination at the individual axon level unclear. Here we demonstrate stimulation somatosensory axons in mouse brain increases proliferation and differentiation oligodendrocyte progenitor cells (OPCs) within underlying white matter. Stimulated display an increased probability being myelinated compared...
Parenchymal oligodendrocyte progenitor cells (pOPCs) are considered the principal cell type responsible for oligodendrogenesis and remyelinaton in demyelinating diseases. Recent studies have demonstrated that neural precursor (NPCs) from adult subventricular zone (SVZ) can also generate new oligodendrocytes after demyelination. However, relative contribution of NPCs versus pOPCs to remyelination is unknown. We used vivo genetic fate mapping assess behavior each within corpus callosi (CCs)...
The critical role of oligodendrocytes in producing and maintaining myelin that supports rapid axonal conduction CNS neurons is well established. More recently, additional roles for have been posited, including provision trophic factors metabolic support neurons. To investigate the functional consequences oligodendrocyte loss, we generated a transgenic mouse model conditional ablation. In this model, are rendered selectively sensitive to exogenously administered diphtheria toxin (DT) by...
Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent CNS have limitations extent and duration of OPC depletion. We developed a pharmacogenetic approach for conditional ablation, eliminating >98% OPCs throughout brain. By combining recombinase-based transgenic viral strategies targeting ventricular-subventricular zone (V-SVZ)-derived neural precursor (NPCs), we found that new PDGFRA-expressing born V-SVZ repopulated OPC-deficient...
Abstract The identification of factors that regulate myelination provides important insight into the molecular mechanisms coordinate nervous system development and myelin regeneration after injury. In this study, we investigated role amyloid precursor protein (APP) its paralogue precursor‐like 2 (APLP2) in using APP APLP2 knockout (KO) mice. Given BACE1 regulates sheath thickness both peripheral central systems, sought to determine if APLP2, as alternate substrates, also modulate...
Rodents, particularly mice and rats, are extensively utilized in fundamental neuroscience research. Brain atlases have played a pivotal role this field, evolving from traditional printed histology to digital incorporating diverse imaging datasets. Magnetic resonance (MRI)-based brain atlases, also known as maps, been employed specific studies. However, the existence of numerous versions MRI-based has impeded their standardized application widespread use, despite consensus within academic...
Low-grade glioma (LGG) is the most common brain tumor affecting pediatric patients (pLGG) and BRAF mutations constitute frequent genetic alterations. Within spectrum of pLGGs, approximately 70%-80% diagnosed with transforming pleomorphic xanthoastrocytoma (PXA) harbor V600E mutation. However, impact cell regulation tumor-infiltrating immune cells their contribution to progression remains unclear. Moreover, efficacy inhibitors in treating pLGGs limited compared on BRAF-mutated melanoma. Here...
ABSTRACT BRAF V600E pediatric low-grade gliomas frequently transform into high-grade (HGG) and poorly respond to chemotherapy, resulting in high mortality. Although combined MEK inhibition (BRAFi+MEKi) outperforms ∼70% of HGG patients are therapy resistant undergo unbridled tumor progression. glioma have an immune-rich microenvironment suggesting that they could be responsive immunotherapy but effects BRAFi+MEKi on anti-tumor immunity unclear. Using patient tissue before after BRAFi+MEKi,...
Abstract In multiple sclerosis (MS), chronic demyelination initiated by immune-mediated destruction of myelin, leads to axonal damage and neuronal cell death, resulting in a progressive decline neurological function. The development interventions that potentiate remyelination could hold promise as novel treatment strategy for MS. To this end, our group has demonstrated neural precursor cells (NPCs) residing the ventricular-subventricular zone (V-SVZ) adult mouse brain contribute...
Desmoplastic infantile ganglioglioma/desmoplastic astrocytoma (DIG/DIA) are low-grade glial/glioneuronal tumors occurring predominantly in the cerebral hemispheres of infants. DIG/DIA exhibit BRAF or RAF1 alterations leading to oncogenic mitogen-activated protein kinase (MAPK) pathway activation. Here, we report discovery novel CDC42BPA::BRAF fusion a three-month-old patient with left frontotemporal DIA using DNA sequencing. Independent validation was performed through RNA This joins domains...
<title>Abstract</title> Brain metastases (BM) occur in 2.3% of patients with colorectal cancer (CRC), which is the second leading cause deaths globally. Despite aggressive treatment like surgery and chemo-irradiation, median survival for BM originating from CRC (CRC-BM) remains poor at 5.3 months, highlighting need improved therapies. Next-generation sequencing has identified <italic>KRAS </italic>mutations approximately 40% metastatic cases. Therapies targeting mutant KRAS downstream MAPK...
Abstract BACKGROUND Despite the availability of targeted therapies, gliomas carrying BRAFV600E mutation remain challenging to treat. Combined pharmacologic and MEK inhibition is clinically used in patients with mutant gliomas, but primary acquired resistance reported ~70% high-grade glioma patients. OBJECTIVES To gain mechanistic insights into therapy adaptation escape for developing combination therapies that enhance clinical effects combined Dabrafenib Trametinib (BRAFi+MEKi) gliomas....
Abstract Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent central nervous system have been limited methodological challenges resulting only partial and transient OPC depletion. We developed a novel pharmacogenetic model of conditional ablation, eliminating 98.6% all OPCs throughout brain. By combining recombinase-based transgenic viral strategies for targeting ventricular-subventricular zone (V-SVZ)-derived neural precursor...
Molecular cloning techniques enabling contemporaneous expression of two or more protein-coding sequences provide an invaluable tool for understanding the molecular regulation cellular functions. The Cre-lox system is used inducing recombinant proteins encoded within a bi-/poly-cistronic cassette. However, leak transgenes often observed in absence Cre recombinase activity, compromising utility this approach. To investigate mechanism expression, we generated Cre-inducible bi-cistronic vectors...
Abstract Colorectal adenocarcinomas (CRC) rarely metastasize to the brain, however, survival rates in patients with colorectal brain metastases (CBM) are short, a median of only 4 months from diagnosis. Currently, no evidence-based treatment options against these rare available (PMC). Therefore, characterization tumors and development targeted therapies imperative. Optimal models for neoplasms heighten notoriously low success rate bench-to-bedside translation. Historically, cancer...
Abstract Molecular cloning techniques enabling contemporaneous expression of two or more protein-coding sequences in a cell type interest provide an invaluable tool for understanding the molecular regulation cellular functions. DNA recombination employing Cre-lox system is commonly used as switch inducing recombinant proteins encoded within bicistronic cassette. In such approach, are separated by 2A peptide internal ribosome entry site (IRES), and designed to be strictly Cre-dependent using...