A5053059447- Chronic Lymphocytic Leukemia Research
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Immunodeficiency and Autoimmune Disorders
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- Acute Myeloid Leukemia Research
- Advanced Breast Cancer Therapies
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Synthetic Organic Chemistry Methods
- Immune Cell Function and Interaction
- Microtubule and mitosis dynamics
- Glycosylation and Glycoproteins Research
- Histone Deacetylase Inhibitors Research
- X-ray Diffraction in Crystallography
- Genomic variations and chromosomal abnormalities
- Cell death mechanisms and regulation
- Crystallization and Solubility Studies
- Protein Degradation and Inhibitors
University of Birmingham
2015-2024
University of Belgrade
2019
University of Nis
2016-2019
Queen Elizabeth Hospital Birmingham
2005-2015
Pfizer (United Kingdom)
2013
University of Basel
2013
University Children’s Hospital Basel
2013
Dana-Farber Cancer Institute
2013
Harvard University
2013
Royal Bournemouth Hospital
2005-2012
Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4, BRDT) are transcriptional regulators required for efficient expression of several growth promoting antiapoptotic genes as well cell-cycle progression. BET recruited on transcriptionally active chromatin via their two N-terminal bromodomains (BRD), a protein interaction module that specifically recognizes acetylated lysine residues in histones H3 H4. Inhibition the BET-histone results downregulation number oncogenes, providing novel...
Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. To explore genetic resistance mechanisms, we performed genome-wide CRISPR-Cas9 screens cells treated with DNA topoisomerase I inhibitor topotecan. Thus, here establish that inactivating terminal components of non-homologous end-joining (NHEJ) machinery or BRCA1-A complex specifically topotecan ATM-deficient cells. We show ATM-mutant poly-(ADP-ribose) polymerase (PARP) olaparib reflects...
The ataxia telangiectasia mutated (ATM) gene is located on chromosome 11q and loss of this region common in B-cell chronic lymphocytic leukemia (CLL). Our aim was to determine if CLL tumors with a deletion might be divided into two subgroups based the status remaining ATM allele.The sequence residual allele determined 72 CLLs an deletion. This related cellular response irradiation or cytotoxic drug exposure vitro clinical outcome.We show that 36% these leukemias demonstrate impaired vitro....
Cellular DNA double-strand break-repair pathways have evolved to protect the integrity of genome from a continual barrage potentially detrimental insults. Inherited mutations in genes that control this process result an inability properly repair damage, ultimately leading developmental defects and also cancer predisposition. Here, we describe patient with previously undescribed syndrome, which termed RIDDLE syndrome (radiosensitivity, immunodeficiency, dysmorphic features learning...
Purpose The prognostic significance of ATM mutations in chronic lymphocytic leukemia (CLL) is unclear. We assessed their impact the context a prospective randomized trial. Patients and Methods analyzed gene 224 patients treated on Leukemia Research Fund Chronic Lymphocytic 4 (LRF-CLL4) trial with chlorambucil or fludarabine without cyclophosphamide. status was by denaturing high-performance liquid chromatography related to treatment response, survival, TP53 alterations for same patient...
The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but preferentially protected transcription-coupled repair
Abstract SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that mutant ( MUT ) cells selectively sensitive poly (ADP-ribose) polymerase inhibitors (PARPi), independent mutation site. display defective response PARPi-induced replication stress occurs via downregulation the cyclin-dependent kinase 2 interacting protein (CINP), leading increased fork origin...
Paediatric B-precursor ALL is a highly curable disease, however, treatment resistance in some patients and the long-term toxic effects of current therapies pose need for more targeted therapeutic approaches. We addressed cytotoxic effect JQ1, selective inhibitor against transcriptional regulators, bromodomain extra-terminal (BET) family proteins, paediatric ALL. showed potent vitro response panel primary to independent their prognostic features but dependent on high MYC expression coupled...