A5043964307- Bladder and Urothelial Cancer Treatments
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- RNA modifications and cancer
- Cancer Research and Treatments
- Urinary and Genital Oncology Studies
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- PARP inhibition in cancer therapy
- Genetic factors in colorectal cancer
- Prostate Cancer Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Protein Degradation and Inhibitors
Newcastle University
2021-2024
University of Oxford
2024
Centre for Human Genetics
2024
Koç University
2015-2021
Ten-eleven translocation enzymes (TETs) are Fe(II)/2-oxoglutarate (2OG) oxygenases that catalyze the sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine in eukaryotic DNA. Despite their roles epigenetic regulation, there is a lack reported TET inhibitors. The extent which 2OG oxygenase inhibitors, including clinically used inhibitors oncometabolites, modulate DNA modifications via TETs has been unclear. Here, we report studies on...
Ten-Eleven Translocation (TET) enzymes are Fe(II)/2OG-dependent oxygenases that play important roles in epigenetic regulation, but selective inhibition of the TETs is an unmet challenge. We describe profiling previously identified TET1-binding macrocyclic peptides. TiP1 established as a potent TET1 inhibitor (IC50 = 0.26 µM) with excellent selectivity over other and 2OG oxygenases. alanine scanning reveals critical Trp10 Glu11 residues for TET isoenzymes. The results highlight utility RaPID...
Abstract Androgen deprivation therapy (ADT) is the standard care for prostate cancer (PCa) patients who fail surgery or radiotherapy. While initially effective, almost always recurs as a more aggressive castration resistant (CRPC). Previous studies have demonstrated that chromatin modifying enzymes can play critical role in conversion to CRPC. However, only handful of these potential pharmacological targets been tested. Therefore, this study, we conducted focused shRNA screen previously...
Synchronous multifocal tumours are commonly observed in urothelial carcinomas of the bladder. The origin these physically independent has been proposed to occur by either intraluminal migration (clonal) or spontaneous transformation multiple cells carcinogens (field effect). It is unclear which model correct, with several studies supporting both hypotheses. A potential cause this uncertainty may be small number genetic mutations previously used quantify relationship between tumours. To...
Abstract 2-Oxoglutarate (2OG) dependent N ε -methyl lysine demethylases (JmjC-KDMs) regulate eukaryotic transcription. We report studies showing that isolated forms of all human KDM4 and KDM5 JmjC enzymes catalyse demethylation -methylated Arg-3 histone H2a. Unexpectedly, the results reveal KDM4E and, less efficiently, KDM4D C-4 hydroxylation Arg-20 H2a on peptides, recombinant H2a, calf extracts, including when guanidino group is -methylated. Combined with previous observations, our...
Abstract Background The detection rate of clinically significant prostate cancer has improved with the use multiparametric magnetic resonance imaging (mpMRI). Yet, even MRI‐guided biopsy 15%–35% high‐risk lesions (Prostate Imaging‐Reporting and Data System [PI‐RADS] 4 5) are histologically benign. It is unclear if these false positives due to diagnostic/sampling errors or pathophysiological alterations. To better understand this, we tested benign PI‐RAD 5 for common malignant epigenetic...