A5058603994- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- Prostate Cancer Treatment and Research
- vaccines and immunoinformatics approaches
- Bioinformatics and Genomic Networks
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Proteoglycans and glycosaminoglycans research
- Acne and Rosacea Treatments and Effects
- Herpesvirus Infections and Treatments
- Canadian Identity and History
- Advanced biosensing and bioanalysis techniques
- melanin and skin pigmentation
University of Cambridge
2020-2025
Wellcome/MRC Cambridge Stem Cell Institute
2023-2025
Wellcome Sanger Institute
2020-2021
Altnagelvin Area Hospital
2016
University of Ulster
2016
Nature has evolved intricate machinery to target and degrade RNA, some of these molecular mechanisms can be adapted for therapeutic use. Small interfering RNAs RNase H-inducing oligonucleotides have yielded agents against diseases that cannot tackled using protein-centered approaches. Because are nucleic acid-based, they several inherent drawbacks which include poor cellular uptake stability. Here we report a new approach RNA small molecules, proximity-induced acid degrader (PINAD). We...
Data-driven computational analysis and simulation identified drug repurposing opportunities for COVID-19.
Progressive macular hypomelanosis (PMH) is a common skin disorder that causes hypopigmentation in variety of types. Although the underlying aetiology this condition unclear, there circumstantial evidence links bacterium Propionibacterium acnes to condition. We now describe first detailed population genetic analysis P. isolates recovered from paired lesional and non-lesional PMH patients. Our results demonstrate strong statistical association between strains type III phylogenetic lineage...
Abstract Receptor-ligand interactions govern a wide array of biological pathways, facilitating cell’s ability to interrogate and integrate information from the extracellular space. Here, using an unbiased genome-wide knockout screen, we identify heparan sulfate proteoglycans (HSPGs) as major component in organizational mechanism cell surface glycoRNA RNA binding proteins (csRBPs). Cleavage mature chains, N- 6- O -sulfotransferases, overexpression endo-6- -sulfatases, or addition exogenous...
METTL1 catalyzes N7-methylation of guanine (m7G) in a subset transfer RNAs (tRNAs). We have shown that is promising therapeutic target for various malignancies, including acute myeloid leukemia (AML), melanoma, and pancreatic ductal adenocarcinoma (PDAC). Here, we present characterization STM9005, novel small-molecule inhibitor METTL1, as an effective strategy against cancer.Aims: To evaluate the potential bioavailable tRNA methyltransferase inhibitor, aggressive malignancies. Methods:...
Abstract Background: Diffuse hemispheric glioma, H3 G34-mutant, is a pediatric-type high-grade glioma with limited treatment options and poor prognosis. RNA-modifying enzymes, including METTL3, are critical for the initiation maintenance of various cancers, brain tumors. We previously presented STM2457, first-in-class enzyme inhibitor targeting catalytic activity preventing m6A deposition on mRNA. Here, we show small-molecule inhibition METTL3 as novel therapeutic strategy G34-mutant...
Abstract Immunotherapies for acute myeloid leukemia (AML) and other cancers are limited by a lack of tumor-specific targets. Here we discover that RNA-binding proteins glycosylated RNAs (glycoRNAs) form precisely organized nanodomains on cancer cell surfaces. We characterize nucleophosmin (NPM1) as an abundant surface protein (csNPM1) variety tumor types. With focus AML, observe csNPM1 blasts leukemic stem cells but not normal hematopoietic cells. develop monoclonal antibody to target...
The RNA methyltransferase METTL1 in complex with the adaptor protein WDR4 is responsible for deposition of N7-methylguanosine at position 46 (m7G46) a subgroup transfer RNAs (tRNAs). m7G46 modification tRNAs mediates their increased structural stability and elevated expression levels, which turn enables translation rates mRNAs enriched codons matching those tRNAs. often found over-expressed cancer tissue, its gene locus frequently amplified tumours. Recent studies have shown that reducing...
Abstract METTL1 is an RNA methyltransferase that catalyzes N7-methylation on guanine at position 46 (m7G46) in a subset of transfer RNAs (tRNAs). These tRNAs are stabilized by m7G46, and this increases the translation mRNAs containing cognate codons. often over-expressed cancer tissue, its gene locus frequently amplified specific tumor types. Recent studies have shown reducing expression leads to growth inhibition highlighting enzyme as potential novel target for anti-cancer drugs. We...
Abstract METTL3 is an RNA methyltransferase which responsible for the deposition of N-6-methyladenosine (m6A) on mRNA targets such as SP1, to modulate their stability and expression. was identified essential gene growth AML cells proposed a novel target cancer therapy (Barbieri 2017). We present in vitro vivo characterization small molecule inhibitors METTL3, recapitulate genetic validation using pharmacological audit trail. Small from 2 distinct chemical series were optimised...
SUMMARY The global outbreak of SARS-CoV-2 necessitates the rapid development new therapies against COVID-19 infection. Here, we present identification 200 approved drugs, appropriate for repurposing COVID-19. We constructed a SARS-CoV-2-induced protein (SIP) network, based on disease signatures defined by multi-omic datasets(Bojkova et al., 2020; Gordon 2020), and cross-examined these pathways drugs. This analysis identified drugs predicted to target pathways, 40 which are already in...
Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Targeting RNA methylation by selective catalytic inhibition of the methyltransferase METTL3 has shown significant promise as a therapeutic strategy against AML. While hematopoietic defects have been reported in KO models, non-catalytic functions are increasingly being recognized, highlighting importance identifying specific effects its inhibition. Here we report first characterization on healthy murine hematopoiesis. Aims:...