A5021787274- Chromatin Remodeling and Cancer
- Mechanisms of cancer metastasis
- Cancer Mechanisms and Therapy
- Cancer-related gene regulation
- Esophageal Cancer Research and Treatment
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Cancer-related molecular mechanisms research
- Gastric Cancer Management and Outcomes
- Epigenetics and DNA Methylation
- Neurofibromatosis and Schwannoma Cases
- Renin-Angiotensin System Studies
- RNA Research and Splicing
- Nuclear Receptors and Signaling
- FOXO transcription factor regulation
- Gastrointestinal Tumor Research and Treatment
- Sarcoma Diagnosis and Treatment
- Helicobacter pylori-related gastroenterology studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Alzheimer's disease research and treatments
- RNA regulation and disease
- CAR-T cell therapy research
- Gene expression and cancer classification
Garvan Institute of Medical Research
2014-2025
C4 Therapeutics (United States)
2025
Memorial Sloan Kettering Cancer Center
2018-2022
Kettering University
2020-2022
UNSW Sydney
2014-2017
St Vincent's Clinic
2016-2017
The Kinghorn Cancer Centre
2017
Uppsala University
2012-2013
The University of Adelaide
2012
Despite the prevalence of long noncoding RNA (lncRNA) genes in eukaryotic genomes, only a small proportion have been examined for biological function. lncRNAdb, available at http://lncrnadb.org, provides users with comprehensive, manually curated reference database 287 lncRNAs that described independently scientific literature. In addition to capturing great recent literature describing functions individual lncRNAs, lncRNAdb now offers an improved user interface enabling greater...
RNA-sequencing has become the gold standard for whole-transcriptome gene expression quantification. Multiple algorithms have been developed to derive counts from sequencing reads. While a number of benchmarking studies conducted, question remains how individual methods perform at accurately quantifying levels We performed an independent study using data well established MAQCA and MAQCB reference samples. reads were processed five workflows (Tophat-HTSeq, Tophat-Cufflinks, STAR-HTSeq,...
Displaying data onto anatomical structures is a convenient technique to quickly observe tissue related information. However, drawing tissues complex task that requires both expertise in anatomy and the arts. While web based applications exist for displaying gene expression on anatograms, other non-genetic disciplines lack similar tools. Moreover, tools often modularity associated with packages programming languages, such as R. Here I present gganatogram, an R package used plot modular...
<ns4:p>Displaying data onto anatomical structures is a convenient technique to quickly observe tissue related information. However, drawing tissues complex task that requires both expertise in anatomy and the arts. While web based applications exist for displaying gene expression on anatograms, other non-genetic disciplines lack similar tools. Moreover, tools often modularity associated with packages programming languages, such as R.</ns4:p><ns4:p>Here I present gganatogram, an R package...
Despite their abundance, the molecular functions of long non-coding RNAs in mammalian nervous systems remain poorly understood. Here we show that RNA, NEAT1, directly modulates neuronal excitability and is associated with pathological seizure states. Specifically, NEAT1 dynamically regulated by activity vitro vivo, binds epilepsy-associated potassium channel-interacting proteins including KCNAB2 KCNIP1, induces a hyper-potentiation phenotype iPSC-derived human cortical neurons following...
Abstract The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die the disease. Here our analyses RNA sequencing data identify long noncoding lncNB1 as one transcripts most over-expressed in -amplified, compared -non-amplified, human cells also all other cancers. binds ribosomal protein RPL35 enhance E2F1 synthesis, leading DEPDC1B gene transcription. GTPase-activating induces ERK phosphorylation stabilization....
Abstract Mutations of subunits the SWI/SNF chromatin remodeling complexes occur commonly in cancers different lineages, including advanced thyroid cancers. Here we show that thyroid-specific loss Arid1a, Arid2, or Smarcb1 mouse BRAFV600E-mutant tumors promotes disease progression and decreased survival, associated with lesion-specific effects on accessibility differentiation. As compared normal thyrocytes, papillary have lineage transcription factor expression to their target DNA binding...
We investigated the role of PRMT5 in myeloproliferative neoplasm (MPN) pathogenesis and aimed to elucidate key targets contributing MPN maintenance. is overexpressed primary cells, inhibition potently reduced cell proliferation ex vivo. was efficacious at reversing elevated hematocrit, leukocytosis, splenomegaly a model JAK2V617F+ polycythemia vera leukocyte platelet counts, hepatosplenomegaly, fibrosis MPLW515L myelofibrosis. Dual targeting JAK superior or inhibitor monotherapy, further...
Genotyping of large populations through genome-wide association studies (GWAS) has successfully identified many genomic variants associated with traits or disease risk. Unexpectedly, a proportion GWAS single nucleotide polymorphisms (SNPs) and haplotype blocks are in intronic intergenic regions, hindering their functional evaluation. While some these risk-susceptibility regions encompass cis-regulatory sites, transcriptional potential never been systematically explored. To detect rare...
Mutations in the ER chaperone calreticulin (CALR) are common myeloproliferative neoplasm (MPN) patients, activate thrombopoietin receptor (MPL), and mediate constitutive JAK/STAT signaling. The mechanisms by which CALR mutations cause myeloid transformation incompletely defined. We used mass spectrometry proteomics to identify CALR-mutant interacting proteins. Mutant caused mislocalization of binding partners increased recruitment FLI1, ERP57, MPL promoter enhance transcription. Consistent...
Long-term potentiation (LTP) of synaptic transmission is recognized as a cellular mechanism for learning and memory storage. Although de novo gene transcription known to be required in the formation stable LTP, molecular mechanisms underlying plasticity remain elusive. Noncoding RNAs have emerged major regulatory molecules that are abundantly specifically expressed mammalian brain. By combining RNA-seq analysis with LTP induction dentate gyrus live rats, we provide first global...
Esophageal adenocarcinoma (EAC) has one of the fastest increases in incidence any cancer, along with poor five-year survival rates. Barrett's esophagus (BE) is main risk factor for EAC; however, mechanisms driving EAC development remain poorly understood. Here, transcriptomic profiling was performed using RNA-sequencing (RNA-seq) on premalignant and malignant tissues to better understand this disease. Machine-learning network analysis methods were applied discover novel driver genes...
Abstract Polycomb repressive complex 2 (PRC2) has oncogenic and tumor-suppressive roles in cancer. There is clinical success of targeting this PRC2-dependent cancers, but an unmet therapeutic need exists PRC2-loss PRC2-inactivating mutations are a hallmark feature high-grade malignant peripheral nerve sheath tumor (MPNST), aggressive sarcoma with poor prognosis no effective targeted therapy. Through RNAi screening MPNST, we found that PRC2 inactivation increases sensitivity to genetic or...
Abstract Tumorigenic drivers of MYCN gene nonamplified neuroblastoma remain largely uncharacterized. Long noncoding RNAs (lncRNAs) regulate tumorigenesis, however, there is little literature on therapeutic targeting lncRNAs with small molecule compounds. Here PRKCQ‐AS1 identified as the lncRNA most overexpressed in nonamplified, compared ‐amplified, cell lines. expression controlled by super‐enhancers, and RNA bound to MSI2 protein. immunoprecipitation sequencing BMX mRNA transcript...
Abstract Background: While MYCN-amplified neuroblastoma has been the focus of research in past three decades, most human neuroblastomas do not harbour MYCN oncogene amplification, and their tumorigenic factors are unknown. Long non-coding RNAs (lncRNAs) regulate tumorigenesis by modulating expression molecular targets, however, there is limited literature on therapeutic targeting lncRNAs with small molecule compounds. Aims: To determine oncogenic mechanism though which lncRNA lncNB promotes...
The c-MYB (MYB) oncogenic transcription factor is a key regulator of hematopoietic cell differentiation and proliferation. Recurrent genetic lesions dysregulation MYB have been identified in variety cancers, including adenoid cystic carcinoma (ACC), acute myeloid leukemia (AML), colorectal cancer (CRC), others. We describe the mechanism action biological activity REM-422, first-in-class, potent, selective, oral small molecule messenger RNA (mRNA) degrader being developed for treatment ACC...
Immune checkpoint blockade (ICB) has demonstrated clinical success in "inflamed" tumors with substantial T cell infiltrates, but an immune-desert tumor microenvironment (TME) fail to benefit. The cell–intrinsic molecular mechanisms of the phenotype remain poorly understood. Here, we that inactivation polycomb-repressive complex 2 (PRC2) core components embryonic ectoderm development (EED) or suppressor zeste 12 homolog (SUZ12), a prevalent genetic event malignant peripheral nerve sheath...