A5057224766- PI3K/AKT/mTOR signaling in cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Estrogen and related hormone effects
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Nutrition, Genetics, and Disease
- Cancer Genomics and Diagnostics
- Ovarian cancer diagnosis and treatment
- Phytoestrogen effects and research
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Blood Coagulation and Thrombosis Mechanisms
- Genomics, phytochemicals, and oxidative stress
- RNA Interference and Gene Delivery
- Protease and Inhibitor Mechanisms
- PARP inhibition in cancer therapy
- Receptor Mechanisms and Signaling
- S100 Proteins and Annexins
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
Breast Cancer Now
2010-2022
King's College London
2018-2022
London Cancer
2018
Institute of Cancer Research
2009-2013
University of Alberta
2013
National Research Centre
2013
Breast Cancer Research Foundation
2013
Breakthrough
2013
Cancer Research Center
2013
Instituto Venezolano de Investigaciones Científicas
2005
Endometrioid endometrial cancer cell lines harboring PTEN loss of function have impaired homologous recombination response to DNA double-strand breaks and show an exquisite sensitivity PARP inhibition.
Abstract The design of targeted therapeutic strategies for cancer has largely been driven by the identification tumor-specific genetic changes. However, large number alterations present in tumor cells means that it is difficult to discriminate between genes are critical maintaining disease state and those merely coincidental. Even when can be identified, directly targeting these often challenging, meaning alternative such as exploiting synthetic lethality may beneficial. To address issues,...
Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance tamoxifen remains major clinical problem. Here we used genome-wide functional profiling approach identify multiple genes confer or sensitivity tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 on cellular response This screen,...
Abstract RNA interference (RNAi) screening is a state-of-the-art technology that enables the dissection of biological processes and disease-related phenotypes. The commercial availability genome-wide, short hairpin (shRNA) libraries has fueled interest in this area but generation analysis these complex data remain challenge. Here, we describe complete experimental protocols novel open source computational methodologies, shALIGN shRNAseq, allow RNAi screens to be rapidly deconvoluted using...
Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies validates gene addictions in TNBCs. CNAs expression alterations are integrated genes scored for pre-specified target features revealing 130 candidate genes. We test functional dependence on each of these using RNAi cancer non-malignant cells, validating malignant cell...
A recent screen of 6,961 siRNAs to discover possible synthetic lethal partners the DNA repair protein polynucleotide kinase/phosphatase (PNKP) led identification potent tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Here, we have confirmed PNKP/PTEN partnership in a variety different cell lines including PC3 prostate cancer line, which is naturally deficient PTEN. We provide evidence that codepletion PTEN PNKP induces apoptosis. In HCT116 colon cells, loss...
PTEN (Phosphatase and tensin homolog) is a tumour suppressor gene commonly defective in human cancer, thus potentially important therapeutic target. Targeting loss-of-function possible by exploiting the genetic concept of synthetic lethality (SL). By combining use isogenic models deficiency with high-throughput RNA interference (RNAi) screening, we have identified Nemo-Like Kinase (NLK) inhibition as being synthetically lethal deficiency. This SL likely mediated transcription factor FOXO1...
Abstract HORMAD1 expression is usually restricted to germline cells, but it becomes mis-expressed in epithelial cells ~60% of triple-negative breast cancers (TNBCs), where associated with elevated genomic instability (1). TNBC bimodal HORMAD1-positive representing a biologically distinct disease group. Identification HORMAD1-driven genetic dependencies may uncover novel therapies for this To study dependencies, we generated SUM159 cell line model doxycycline-inducible that replicated...
5065 Background: Loss of function PTEN is the most common genetic defect in endometroid endometrial carcinomas (EEC). plays a pivotal role regulation AKT and mTOR signalling pathways reported to be inactivated up 80% EECs. loss has recently been shown cause instability through defects homologous recombination (HR) DNA repair double strand breaks. Cancer cells with defective HR have an exquisite sensitivity inhibitors poly(ADP) ribose polymerase (PARP) inhibitors. Recent data suggest...
<p>PDF file, 110K, Supplementary Figure S1. Determination of ROS production in PTEN+/+ and PTEN-/- cells; S2. Cell proliferation assay the PC3 derived cell lines.</p>
<div>Abstract<p>A recent screen of 6,961 siRNAs to discover possible synthetic lethal partners the DNA repair protein polynucleotide kinase/phosphatase (PNKP) led identification potent tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (<i>PTEN</i>). Here, we have confirmed PNKP/PTEN partnership in a variety different cell lines including PC3 prostate cancer line, which is naturally deficient PTEN. We provide evidence that codepletion PTEN PNKP...
<div>Abstract<p>A recent screen of 6,961 siRNAs to discover possible synthetic lethal partners the DNA repair protein polynucleotide kinase/phosphatase (PNKP) led identification potent tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (<i>PTEN</i>). Here, we have confirmed PNKP/PTEN partnership in a variety different cell lines including PC3 prostate cancer line, which is naturally deficient PTEN. We provide evidence that codepletion PTEN PNKP...
<p>PDF file, 110K, Supplementary Figure S1. Determination of ROS production in PTEN+/+ and PTEN-/- cells; S2. Cell proliferation assay the PC3 derived cell lines.</p>
<p>PDF file - 3567K</p>
Press Conference from Functional Viability Profiles of Breast Cancer
Press Conference from Functional Viability Profiles of Breast Cancer
<p>PDF file - 3567K</p>
<div>Abstract<p>The design of targeted therapeutic strategies for cancer has largely been driven by the identification tumor-specific genetic changes. However, large number alterations present in tumor cells means that it is difficult to discriminate between genes are critical maintaining disease state and those merely coincidental. Even when can be identified, directly targeting these often challenging, meaning alternative such as exploiting synthetic lethality may beneficial....
<div>Abstract<p>The design of targeted therapeutic strategies for cancer has largely been driven by the identification tumor-specific genetic changes. However, large number alterations present in tumor cells means that it is difficult to discriminate between genes are critical maintaining disease state and those merely coincidental. Even when can be identified, directly targeting these often challenging, meaning alternative such as exploiting synthetic lethality may beneficial....
Abstract In order to identify novel tumor drivers and gene addictions in breast cancer we have recently completed an integrated silico/in vitro analysis of copy-number alterations gene-expression profiles a Triple Negative Breast Cancer-enriched cohort. An amplified overexpressed that appeared be driver required for cell proliferation is GPHR/GPR89. Several lines evidence suggested GPHR anion channel, resident the Golgi, where it controls intraluminal pH. Perturbation function leads altered...