A5001015289- Acute Lymphoblastic Leukemia research
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- TGF-β signaling in diseases
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Genomic variations and chromosomal abnormalities
- Protease and Inhibitor Mechanisms
- Click Chemistry and Applications
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Immunodeficiency and Autoimmune Disorders
- Williams Syndrome Research
- Cancer Research and Treatments
- Barrier Structure and Function Studies
- Genetic factors in colorectal cancer
- T-cell and Retrovirus Studies
- Eosinophilic Disorders and Syndromes
- Nuclear Receptors and Signaling
- Pancreatic and Hepatic Oncology Research
- Gender, Feminism, and Media
- Genomics and Chromatin Dynamics
Wrightington, Wigan and Leigh NHS Foundation Trust
2021
University of Manchester
2007-2019
St Mary's Hospital
2005-2019
AbbVie (United States)
2018
Meharry Medical College
2010-2014
Manchester Academic Health Science Centre
2011-2012
Health Sciences Centre
2011
Cancer Research UK Manchester Institute
2008
National Cancer Institute
2005
Eastman Dental Hospital
2005
Craniofacial abnormalities account for about one-third of all human congenital defects, but our understanding the genetic mechanisms governing craniofacial development is incomplete. We show that GTF2IRD1 a determinant mammalian and cognitive development, we implicate another member TFII-I transcription factor family, GTF2I , in both aspects. Gtf2ird1 -null mice exhibit phenotypic reminiscent microdeletion disorder Williams-Beuren syndrome (WBS); imaging reveals skull jaws may arise through...
Antibody-drug conjugates (ADC) have emerged as potent antitumor drugs that provide increased efficacy, specificity, and tolerability over chemotherapy for the treatment of cancer. ADCs generated by targeting cysteines lysines on antibody shown but these products are heterogeneous, instability may limit their dosing. Here, a novel technology is described enables site-specific conjugation toxins to antibodies using chemistry produce homogeneous, potent, highly stable conjugates. We developed...
Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for largest subtype ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases 7224 controls). After genotyping an additional 2525 3575 controls, BCP-ALL mapping 10q26.13 (rs35837782,...
Abstract Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much the heritable risk remains unidentified. Here, we perform a GWAS and conduct meta-analysis with two existing GWAS, totaling 2442 cases 14,609 controls. We identify loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10 −9 , odds ratio (OR) 1.34) ETV6-RUNX1 fusion-positive 2q22.3 (rs17481869, 3.20 −8 OR 2.14). Our findings...
Our goal in this study was to define the mechanisms by which fetuin‐A mediates adhesion of tumor cells. The data show that absence fetuin‐A, detached cells secrete exosomes contain most known exosomal associated proteins but lack capacity mediate cellular adhesion. In presence exosomes, contain, addition other proteins, plasminogen and histones. These cell spreading. Plasminogen is a participant novel mechanism. suggest these play role progression.
The expression of annexin A6 (AnxA6) in AnxA6-deficient non-invasive tumor cells has been shown to terminate epidermal growth factor receptor (EGFR) activation and downstream signaling. However, as a scaffolding protein, AnxA6 may stabilize activated cell-surface receptors promote cellular processes such cell motility invasiveness. In this study, we investigated the contribution activity EGFR invasive breast cancer examined whether status influences response these EGFR-targeted tyrosine...
Antibody–drug conjugates (ADCs) have become a powerful platform to deliver cytotoxic agents selectively cancer cells. ADCs traditionally been prepared by stochastic conjugation of drug using an antibody's native cysteine or lysine residues. Through strategic selection the mammalian expression host, we were able introduce azide-functionalized glycans onto homogeneously glycosylated anti-EphA2 monoclonal antibody in one step. Conjugation with alkyne-bearing pyrrolobenzodiazepine dimer payload...
Abstract Genome-wide association studies (GWAS) have provided strong evidence for inherited predisposition to childhood acute lymphoblastic leukaemia (ALL) identifying a number of risk loci. We previously shown common SNPs at 9p21.3 influence ALL risk. These SNP associations are generally not themselves candidates causality, but simply act as markers functional variants. By means imputation GWAS data and subsequent validation genotyping totalling 2,177 cases 8,240 controls, we that the can...
Antibody-drug conjugates (ADCs) have emerged as an important class of therapeutics for cancer treatment that combine the target specificity antibodies with killing activity anticancer chemotherapeutics. Early conjugation technologies relied upon random to either lysine or cysteine residues, resulting in heterogeneous ADCs. Recent technology advancements resulted preparation homogeneous ADCs through site-specific at engineered cysteines, glycosylated amino acids, and bioorthogonal unnatural...
Mammals are able to rapidly produce red blood cells in response stress. The molecular pathways used this process important understanding responses anaemia multiple biological settings. Here we characterise the novel gene Claudin 13 (Cldn13), a member of family tight junction proteins using RNA expression, microarray and phylogenetic analysis. We present evidence that Cldn13 appears be co-ordinately regulated as part stress induced erythropoiesis pathway is mouse-specific mainly expressed...
GTF2IRD1 is a member of family transcription factors whose defining characteristic varying numbers helix–loop–helix like motif, the I‐repeat. Here, we present functional analysis human in regulation three genes ( HOXC8 , GOOSECOID and TROPONIN I SLOW ). We define regulatory motif (GUCE–GTF2IRD1 Upstream Control Element) common to all genes. GUCE bound vitro by domain I‐4 mediates transcriptional vivo. Definition this site will assist identification other downstream targets elucidation its...
Childhood Acute Lymphoblastic Leukemia (ALL) is a malignant lymphoid disease of which B-cell precursor- (BCP) and T-cell- (T) ALL are subtypes. The role alleles encoded by major histocompatibility loci (MHC) have been examined in number previous studies results indicating weak, multi-allele associations between the HLA-DPB1 locus BCP-ALL suggested for immunosusceptibility possibly infection. Two independent SNP association identified approximately 37 kb from one another flanking strong...
Abstract Antibody drug conjugates (ADCs) combine the specificity of antibodies with potent cytotoxicity small molecule drugs and have shown to provide therapeutic options for various cancers. We report herein discovery a HER2-targeting ADC MEDI4276 that showed cell killing activity in vitro cancer lines express HER2 receptor. The observed translated into vivo tumor growth inhibition xenograft mouse models. is homogeneous precise control loading following site specific conjugation cytotoxic...