A5078981002- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Reproductive Biology and Fertility
- RNA Research and Splicing
- TGF-β signaling in diseases
- Kruppel-like factors research
- RNA modifications and cancer
- Ovarian cancer diagnosis and treatment
- Microtubule and mitosis dynamics
- Multiple Myeloma Research and Treatments
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- Cancer Cells and Metastasis
- Acute Myeloid Leukemia Research
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Chronic Myeloid Leukemia Treatments
- Extracellular vesicles in disease
- Genomics and Chromatin Dynamics
- Cell death mechanisms and regulation
- Cancer Genomics and Diagnostics
- Caveolin-1 and cellular processes
Monash University
2021-2025
University of Colorado Boulder
2022-2024
Alfred Health
2021-2024
The University of Sydney
2014-2022
Centenary Institute
2018-2022
Royal North Shore Hospital
2014-2020
UNSW Sydney
2013
Garvan Institute of Medical Research
2010
microRNAs have emerged as powerful regulators of many biological processes, and their expression in cancer tissues has been shown to correlate with clinical parameters such type prognosis. Present a variety fluids, described 'gold mine' potential noninvasive biomarkers. Release microRNA content blood cells upon hemolysis dramatically alters the profile blood, potentially affecting levels significant number proposed biomarker and, consequently, accuracy serum or plasma-based tests. Several...
Randomized trials in acute myeloid leukemia (AML) have demonstrated improved survival by the BCL-2 inhibitor venetoclax combined with azacitidine older patients, and clinical are actively exploring role of combination intensive chemotherapy fitter patients AML. As most still develop recurrent disease, understanding relapse mechanisms is needed. We find that 17% relapsing after venetoclax-based therapy for AML acquired inactivating missense or frameshift/nonsense mutations apoptosis effector...
Breast cancers display phenotypic and functional heterogeneity several lines of evidence support the existence cancer stem cells (CSCs) in certain breast cancers, a minor population capable tumor initiation metastatic dissemination. Identifying factors that regulate CSC phenotype is therefore important for developing strategies to treat disease. The Inhibitor Differentiation Protein 1 (Id1) its closely related family member 3 (Id3) (collectively termed Id) are expressed by diversity required...
We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence increase ovarian cancer chemoresistance. The goal of this work was better understand mechanisms NFATC4-driven chemoresistance.We used RNA sequencing identify NFATC4-mediated differential gene expression. CRISPR-Cas9 and FST (follistatin)-neutralizing antibodies were assess impact loss function on cell proliferation ELISA quantify induction patient samples vitro chemotherapy.We...
Abstract Many of the biological functions performed by RNA are mediated RNA-binding proteins (RBPs), and understanding molecular basis these interactions is fundamental to biology. Here, we present massively parallel assay combined with immunoprecipitation (MPRNA-IP) for in vivo high-throughput dissection RNA–protein describe statistical models identifying domains parsing structural contributions RNA. By using custom pools tens thousands sequences containing systematically designed...
Vast transcriptomics and epigenomics changes are characteristic of human cancers, including leukaemia. At remission, we assume that these normalise so omics-profiles resemble those healthy individuals. However, an in-depth transcriptomic epigenomic analysis cancer remission has not been undertaken. A striking exemplar targeted induction occurs in chronic myeloid leukaemia (CML) following tyrosine kinase inhibitor (TKI) therapy. Using RNA sequencing whole-genome bisulfite sequencing, profiled...
The accumulation of poorly differentiated cells is a hallmark breast neoplasia and progression. Thus an understanding the factors controlling mammary differentiation critical to proper tumourigenesis. Inhibitor Differentiation 1 (Id1) protein has well documented roles in control epithelial proliferation vitro cancer progression vivo. However, it not been determined whether Id1 expression sufficient for inhibition or promotion neoplastic transformation We now show that commonly expressed by...
Chimeric RNAs are often associated with chromosomal rearrangements in cancer. In addition, they also widely detected normal tissues, contributing to transcriptomic complexity. Despite their prevalence, little is known about the characteristics and functions of chimeric RNAs. Here, we examine genetic structure biological roles CLEC12A-MIR223HG, a novel transcript produced by fusion cell surface receptor CLEC12A miRNA-223 host gene (MIR223HG), first identified chronic myeloid leukemia (CML)...
Abstract Background After many years of neglect in the field alternative splicing, importance intron retention (IR) cancer has come into focus following landmark discoveries aberrant IR patterns cancer. Many solid and liquid tumours are associated with drastic increases IR, such have been pursued as both biomarkers therapeutic targets. Paradoxically, breast (BrCa) is only tumour type which reduced compared to adjacent normal tissue. Methods In this study, we conducted a pan-cancer analysis...
Abstract Background Vast transcriptomics and epigenomics changes are characteristic of human cancers including leukemia. At remission, we assume that these normalise so omics-profiles resemble those healthy individuals. However, an in-depth transcriptomic epigenomic analysis cancer remission has not been undertaken. A striking exemplar targeted induction occurs in chronic myeloid leukemia (CML) following tyrosine kinase inhibitor (TKI) therapy. Methods Using RNA sequencing whole-genome...
Chemoresistance is a major driver of cancer deaths. One understudied mechanism chemoresistance quiescence. We used single cell culture to identify, retrieve, and RNA-Seq profile primary quiescent ovarian cells (qOvCa). found that many qOvCa differentially expressed genes are transcriptional targets the Myocardin Related Transcription Factor/Serum Response Factor (MRTF/SRF) pathway. also genetic disruption MRTF-SRF interaction, or an MRTF/SRF inhibitor (CCG257081) impact gene expression...
Abstract Breast cancers display phenotypic and functional heterogeneity several lines of evidence support the existence cancer stem cells (CSCs) in certain breast cancers, a minor population capable tumor initiation metastatic dissemination. Identifying factors that regulate CSC phenotype is therefore important for developing strategies to treat disease. The Inhibitor Differentiation Protein 1 (Id1) its closely related family member 3 (Id3) (collectively termed Id) are expressed by diversity...
ABSTRACT Many of the biological functions performed by RNA are mediated RNA-binding proteins (RBPs), and understanding molecular basis these interactions is fundamental to biology. Here, we present MPRNA-immunoprecipitation (MPRNA-IP), an adaptation previously developed massively parallel assay (MPRNA), a new avenue for in vivo high-throughput dissection RNA-protein interactions. By using custom pools tens thousands sequences containing systematically designed truncations mutations, able...
<div>AbstractPurpose:<p>We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence increase ovarian cancer chemoresistance. The goal of this work was better understand mechanisms NFATC4-driven chemoresistance.</p>Experimental Design:<p>We used RNA sequencing identify NFATC4-mediated differential gene expression. CRISPR-Cas9 and FST (follistatin)-neutralizing antibodies were assess impact loss function on cell...
<div>AbstractPurpose:<p>We recently reported that the transcription factor NFATC4, in response to chemotherapy, drives cellular quiescence increase ovarian cancer chemoresistance. The goal of this work was better understand mechanisms NFATC4-driven chemoresistance.</p>Experimental Design:<p>We used RNA sequencing identify NFATC4-mediated differential gene expression. CRISPR-Cas9 and FST (follistatin)-neutralizing antibodies were assess impact loss function on cell...
<p>Supplementary Figure 4. The effect of ATF2 siRNA on gene expression and PT340 FST induced chemoresistance. A. Schematic detailing the transwell experiments. CellTrace Violet cells were sorted for rapidly dividing (Dim) or quiescent (Bright) which then plated in chambers either as Dim:Dim Bright:Dim. Cells untreated treated with taxol alone combination IgG anti-FST antibody. Cell counts performed dim data was expressed fold chnage. B. Relative PT412 scrambled two independent siRNAs...
<p>Supplementary Table 1. Primers used in this study.</p>
<p>Supplementary Figure 3. The effect of FST or taxol treatment ovarian cancer proliferation and secretion, the ability a neutralization antibody to inhibit FST's on proliferation. A. PT340 PT412 cells were treated with 200 ng/mL for 72h before cell counts performed. B (i) IHC images (ii) FST+ bodies in OVSAHO tumor xenografts without stained both Ki67 (Forangi Blue) (Fast Red). C. Titer anti-FST neutralizing growth.</p>
<p>Supplementary Figure 5. Schematic of FST CRISPR KO guides and in vivo experiment. A. Binding the two commercially available to mediate KO. B. Mice were injected with SKOV3 cells expressing sgRNA #2. then treated 3 times 10mg/kg Taxol intraperitoneal Paclitaxel at days 7, 14 21. C Dissection control mice presenting multiple metastases an FST-KO which showed no residual disease. White arrows point sites disease.</p>