Matthew D. Dun
A5018119432- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Sperm and Testicular Function
- Neuroblastoma Research and Treatments
- Reproductive Biology and Fertility
- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Advanced Proteomics Techniques and Applications
- MicroRNA in disease regulation
- Heat shock proteins research
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- Extracellular vesicles in disease
- Radiomics and Machine Learning in Medical Imaging
- Histone Deacetylase Inhibitors Research
- RNA Research and Splicing
- Acute Lymphoblastic Leukemia research
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Mass Spectrometry Techniques and Applications
- Single-cell and spatial transcriptomics
- Chronic Myeloid Leukemia Treatments
University of Newcastle Australia
2016-2025
Hunter Medical Research Institute
2016-2025
Suzhou Municipal Hospital
2024
Suzhou Vocational Health College
2024
Hunter Cancer Research Alliance
2014-2023
University of Delaware
2022
Naval University of Engineering
2019
Nanjing Forestry University
2018
Callaghan Innovation
2016
University of Groningen
2010-2015
Rapid input-restricted change in gene expression is an important aspect of synaptic plasticity requiring complex mechanisms post-transcriptional mRNA trafficking and regulation. Small non-coding miRNA are uniquely poised to support these functions by providing a nucleic-acid-based specificity component for universal-sequence-dependent RNA binding complexes. We investigated the subcellular distribution molecules resting potassium chloride depolarized human neuroblasts, found both selective...
Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3-specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), first-in-human phase I trial administering repeated locoregional CAR cells to children with recurrent/refractory CNS tumors DIPG. Here, report the results of first three...
Abstract Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized adults. Their potential heterogeneity at different ages and locations is vastly understudied. Here, through dissecting single-cell transcriptomic, epigenomic spatial architectures a comprehensive cohort patient H3-K27M DMGs, we delineate how age anatomical location shape glioma cell-intrinsic -extrinsic features light...
Abstract Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated two completed multisite studies. following initial radiation prior to recurrence a median overall survival of 21.7 months, whereas those after had 9.3...
Abstract Background Pediatric diffuse midline gliomas (DMGs) are incurable childhood cancers. The imipridone ONC201 has shown early clinical efficacy in a subset of DMGs. However, the anticancer mechanisms and its derivative ONC206 have not been fully described Methods DMG models including primary human vitro (n = 18) vivo (murine zebrafish) models, patient 20) frozen FFPE specimens were used. Drug-target engagement was evaluated using silico ChemPLP thermal shift assay. Drug toxicity...
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine (DIPG), are the most lethal of childhood cancers. Palliative radiotherapy is only established treatment, with median patient survival 9 to 11 months. ONC201 a DRD2 antagonist and ClpP agonist that has shown preclinical emerging clinical efficacy in DMG. However, further work needed identify mechanisms response DIPGs treatment determine whether recurring genomic features influence response. Using systems-biological approach,...
DNA repair has long been considered impossible in human spermatozoa due to the high level of compaction observed these cells. However, detailed examination base excision pathway revealed presence an enzyme critical this pathway, OGG1. This glycosylase was associated with sperm nucleus and mitochondria could actively excise 8-hydrdoxy, 2′-deoxyguanosine, releasing adduct into extracellular space. activity significantly reduced cadmium (II), a recognized inhibitor OGG1, time- dose- dependent...
The functional maturation of spermatozoa that is necessary to achieve fertilization occurs as these cells transit through the epididymis, a highly specialized region male reproductive tract. A defining feature this process it in complete absence nuclear gene transcription or de novo, protein translation spermatozoa. Rather, driven by sequential interactions between and complex external milieu which they are bathed within lumen epididymal tubule. dynamic microenvironment epididymosomes, small...
Sperm-oocyte interactions are among the most remarkable processes in cell biology. These cellular recognition events initiated by an exquisitely specific adhesion of free-swimming spermatozoa to zona pellucida, acellular matrix that surrounds ovulated oocyte. Decades research focusing on this interaction have led establishment a widely held paradigm pellucida receptor is single molecular entity constitutively expressed sperm surface. In contrast, we employed techniques blue...
The mammalian epididymis is responsible for the provision of a highly specialized environment in which spermatozoa acquire functional maturity and are subsequently stored preparation ejaculation. Making important contributions to both processes epididymosomes, small extracellular vesicles released from epididymal soma via an apocrine secretory pathway. While considerable effort has been focused on defining cargo transferred between epididymosomes spermatozoa, comparatively less known about...
Diffuse midline glioma (DMG), including those of the brainstem (diffuse intrinsic pontine glioma), are pediatric tumors central nervous system (CNS). Recognized as most lethal all childhood cancers, palliative radiotherapy remains only proven treatment option, however, even for that respond, survival is temporarily extended. DMG harbor an immunologically "cold" tumor microenvironment (TME) with few infiltrating immune cells. The mechanisms underpinning cold TME not well understood. Low...
Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine – DIPG), are uniformly fatal brain that lack effective treatment. Analysis of CRISPR-Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across DIPG patient models, highlighting therapeutic potential blood-brain barrier penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At human equivalent maximum tolerated dose, mice treated with paxalisib...
Abstract Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers median survival of 11 months. As B7-H3 expressed on pediatric CNS tumors, we conducted BrainChild-03, single-center, dose-escalation phase 1 clinical trial repetitive intracerebroventricular (ICV) dosing B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR cells) for children with recurrent or refractory tumors and DIPG. Here report results from Arm C, restricted to patients...
Mutations in the interleukin-7 receptor (IL7R) or Janus kinase 3 (JAK3) occur frequently T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation development of T-ALL mouse models. However, signal transduction pathways downstream JAK3 mutations remain poorly characterized. Here we describe phosphoproteome JAK3(L857Q)/(M511I) activating transformed Ba/F3 lymphocyte cells. Signaling regulated by mutants were assessed following inhibition JAK1/JAK3 using...
Post-testicular sperm maturation and storage within the epididymis is a key determinant of gamete quality fertilization competence. Here we demonstrate that mouse spermatozoa possess complex small non-protein-coding RNA (sRNA) profile, composition which markedly influenced by their epididymal transit. Thus, although microRNAs (miRNAs) are highly represented in proximal epididymis, this sRNA class largely diminished mature distal epididymis. Coincident with this, substantial enrichment...
Abstract To facilitate intercellular communication, cells release nano-sized, extracellular vesicles (EVs) to transfer biological cargo both local and distant sites. EVs are enriched in tetraspanins, two of which (CD9 CD151) have altered expression patterns many solid tumours, including prostate cancer, as they advance toward metastasis. We aimed determine whether from with CD9 CD151 could influence cellular behaviour increase the metastatic capabilities non-tumourigenic cells. were isolated...