A5081085768- Acute Myeloid Leukemia Research
- Advanced Proteomics Techniques and Applications
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Ubiquitin and proteasome pathways
- Sperm and Testicular Function
- Glioma Diagnosis and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- PARP inhibition in cancer therapy
- Multiple Myeloma Research and Treatments
- Immune cells in cancer
- Histone Deacetylase Inhibitors Research
- Synthetic Organic Chemistry Methods
- Reproductive Biology and Fertility
- DNA Repair Mechanisms
- Acute Lymphoblastic Leukemia research
- CRISPR and Genetic Engineering
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Mast cells and histamine
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
Vanderbilt University
2025
University of Newcastle Australia
2013-2024
Hunter Medical Research Institute
2015-2024
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...
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...
The seminal vesicles are male accessory sex glands that contribute the major portion of plasma in which mammalian spermatozoa bathed during ejaculation. In addition to conveying sperm through ejaculatory duct, vesicle secretions support survival after ejaculation, and influence female reproductive tract promote receptivity pregnancy. Analysis fluid (SVF) composition by proteomics has proven challenging, due its highly biased protein signature with a small subset dominant proteins difficulty...
Mutations in the type III receptor tyrosine kinase FLT3 are frequent patients with acute myeloid leukemia (AML) and associated a poor prognosis. AML is characterized by overproduction of reactive oxygen species (ROS), which can induce cysteine oxidation redox-sensitive signaling proteins. Here, we sought to characterize specific pathways affected ROS assessing oncogenic primary samples. The or phosphorylation proteins that mediate growth proliferation was increased samples from patient...
Abstract Background and objective Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness death worldwide. Current treatments aim to control symptoms with none able reverse or stop its progression. We explored major molecular changes in COPD pathogenesis. Methods employed quantitative label‐based proteomics map lung tissue proteome cigarette smoke‐induced experimental that induced over 8 weeks progresses 12 weeks. Results Quantification 7324 proteins enabled...
Acute myeloid leukemia (AML) is the most common and aggressive form of acute leukemia, with a 5-year survival rate just 24%. Over third all AML patients harbor activating mutations in kinases, such as receptor tyrosine kinases FLT3 (receptor-type tyrosine-protein kinase FLT3) KIT (mast/stem cell growth factor kit). are associated poor clinical outcomes lower remission rates response to standard-of-care chemotherapy. We have recently identified that core non-homologous end joining DNA repair...
Brain endothelial cells experience mechanical forces in the form of blood flow-mediated shear stress and underlying matrix stiffness, but intersectional contributions these factors towards blood-brain barrier (BBB) impairment neurovascular dysfunction have not been extensively studied. Here, we developed vitro models to examine sensitivity primary human brain microvascular (BMECs) substrate with or without exposure fluid stress. Using a combination molecular profiling techniques, show that...
Microfluidic devices are defined by the application of fluid flow to micron-scale features. Inherent most experiments involving microfluidic is need precisely and reproducibly control at microliter scale, often through multiple inlet ports on a single device. While number channels per device varies, perfusing inputs requires either use controllers (often syringe or peristaltic pumps) ability evenly divide across outlets. Towards latter approach, while handful commercial systems exist for...
The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely characterised. UVA UVB components of sunlight are implicated in melanomagenesis; majority studies have focused on effects UVC light. Interestingly, tumour sequencing has revealed an overrepresentation mutations signature unrepaired UV-induced DNA damage. Repair UVA-induced damage thought to occur primarily through Nucleotide Excision (NER) pathway, which...
Identification of recurrent driver mutations in genes encoding tyrosine kinases has resulted the development molecularly targeted strategies designed to improve outcomes for patients diagnosed with acute myeloid leukemia (AML). The receptor kinase FLT3, is most commonly mutated gene AML, internal tandem duplications within juxtamembrane domain (FLT3-ITD) or missense (FLT3-TKD), present 30%-35% AML at diagnosis. An established mutation and marker poor prognosis, FLT3 emerged as an attractive...
Global high-throughput phosphoproteomic profiling is increasingly being applied to cancer specimens identify the oncogenic signaling cascades responsible for promoting disease initiation and progression; pathways that are often invisible genomics analysis. Hence, has enormous potential inform improve individualized anti-cancer treatment strategies. However, achieve adequate depth coverage necessary activated, hence, targetable kinases driving pathways, affinity phosphopeptide enrichment...
Nucleotide excision repair (NER) orchestrates the of helix distorting DNA damage, induced by both ultraviolet radiation (UVR) and cisplatin. There is evidence that global genome (GGR) arm NER dysfunctional in melanoma it known to have limited induction cell lines after cisplatin treatment. The aims this study were examine mRNA transcript levels regulators GGR investigate downstream effect on expression treatment tumours. regulators, BRCA1 PCNA, melanocytes cisplatin, but not lines....
Abstract Residing between the testes and vas deferens, epididymis is a highly convoluted tubule whose unique luminal microenvironment crucial for functional maturation of spermatozoa. This created by combined secretory resorptive activity lining epididymal epithelium, including release extracellular vesicles (epididymosomes), which encapsulate fertility modulating proteins myriad small non‐coding RNAs (sncRNAs) that are destined delivery to recipient sperm cells. To enable investigation this...
Abstract Fibroblasts are the most common cell type in stroma and function support repair of tissues. Mouse embryonic fibroblasts (MEFs) amenable to isolation rapid growth culture. MEFs therefore widely used as a standard model for functional characterisation gene knockouts, can also be co‐cultures, commonly stem cultures. To facilitate their use research tool, we have performed comprehensive proteomic phosphoproteomic wild‐type primary from C57BL/6 mice. EIF2/4 MTOR signalling pathways were...
Abstract FLT3-mutations are diagnosed in 25-30% of patients with acute myeloid leukemia (AML) and associated a poor prognosis. AML is the overproduction reactive oxygen species (ROS), which drives genomic instability through oxidation DNA bases, promoting clonal evolution, treatment resistance outcomes. ROS also important second messengers, triggering cysteine redox sensitive signaling proteins, however, specific pathways influenced by remain enigmatic. Here we have surveyed...
Abstract DNA hypomethylating agents (HMAs) are used to treat acute myeloid leukemia (AML) and myelodysplasia patients who unsuitable for intensive chemotherapy. However, low response rates therapy-resistant relapse remain significant challenges. To improve outcomes, we must understand how AML cells survive HMA treatment continue proliferate following therapy. We combine single-cell multiomics with parallel colony-forming assays link HMA-induced heterogeneity functional consequences in...
The CD117 mast/stem cell growth factor receptor tyrosine kinase (KIT) is critical for haematopoiesis, melanogenesis and stem maintenance. KIT commonly activated by mutation in cancers including acute myeloid leukaemia, melanoma gastrointestinal stromal tumours (GISTs). the juxtamembrane domains of are hotspots; with domain D816V common leukaemia V560G GISTs. Given importance mutant signalling cancer, we have conducted a proteomic phosphoproteomic analysis progenitor cells expressing D816V-...
The epididymis has long been of interest owing to its role in promoting the functional maturation male germline. More recent evidence also implicated as an important sensory tissue responsible for remodeling sperm epigenome, both under physiological conditions and response diverse forms environmental stress. Despite this knowledge, intricacies molecular pathways involved regulating adaptation epididymal paternal stressors remains be fully resolved.
ABSTRACT Alterations in the FMS-like tyrosine kinase 3 (FLT3) gene are most frequent driver mutations acute myeloid leukaemia (AML), linked to a high risk of relapse patients with internal tandem duplications (FLT3-ITD). Tyrosine inhibitors (TKIs) targeting FLT3 protein approved for clinical use, yet resistance often emerges. This is mainly seen following acquisition additional point domain (TKD), resulting double mutant FLT3-ITD/TKD, which sustains cell signalling and survival despite...
Acute myeloid leukemia (AML) is an aggressive and poor-prognosis blood cancer. Despite a low mutation burden compared to other cancers, AML heterogenous identifying robust therapeutic targets has been difficult. Genomic profiling greatly advanced our understanding of AML, revealed for therapy. However, only 50% patients have gene mutations that are currently druggable, relapse rates remain high. The addition proteomic emerging address these challenges.