A5001494140- Lung Cancer Treatments and Mutations
- Ubiquitin and proteasome pathways
- Micro and Nano Robotics
- HER2/EGFR in Cancer Research
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- Catalytic Processes in Materials Science
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- Zeolite Catalysis and Synthesis
- Fluid Dynamics and Heat Transfer
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Pickering emulsions and particle stabilization
- Chemical Synthesis and Characterization
- Nonlinear Dynamics and Pattern Formation
- Cancer-related gene regulation
- Mesoporous Materials and Catalysis
- Histone Deacetylase Inhibitors Research
- Cancer Research and Treatments
- High-pressure geophysics and materials
- Microfluidic and Bio-sensing Technologies
- Protein Kinase Regulation and GTPase Signaling
University of Bristol
2022-2025
Brown University
2021-2023
University of Oxford
2001-2021
Massachusetts Institute of Technology
2018-2021
University of Limerick
2017
University of Dhaka
2017
Stony Brook University
2015
Stony Brook Medicine
2015
Ono Pharmaceutical (United States)
2011
University of Manchester
2003-2007
Abstract Treatment of second- and third-line patients with non–small-cell lung carcinoma (NSCLC) the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib significantly increased survival relative to placebo. Whereas patient tumors EGFR mutations have shown responses inhibitors, an exclusive role for in benefit from inhibition is unclear. Here we show that wild-type EGFR–containing human NSCLC lines grown both culture as xenografts a range sensitivities dependent on degree which...
Abstract We show that two commonly occurring epidermal growth factor receptor (EGFR) somatic mutations, L858R and an in-frame deletion mutant, Del(746-750), exhibit distinct enzymatic properties relative to wild-type EGFR are differentially sensitive erlotinib. Kinetic analysis of the purified intracellular domains Del(746-750) reveals both mutants active but a higher KM for ATP lower Ki erlotinib receptor. When expressed in NR6 cells, cell line does not express or other ErbB receptors,...
Resistance to androgen receptor (AR) blockade in castration-resistant prostate cancer (CRPC) is associated with sustained AR signaling, including through alternative splicing of (AR-SV). Inhibitors transcriptional coactivators that regulate activity, the paralog histone acetyltransferase proteins p300 and CBP, are attractive therapeutic targets for lethal cancer. Herein, we validate targeting p300/CBP as a strategy describe CCS1477, novel small-molecule inhibitor conserved bromodomain. We...
Epithelial-mesenchymal transition (EMT) is an important contributor to the invasion and metastasis of epithelial-derived cancers. While considerable effort has focused in regulators involved process, we have on consequences EMT prosurvival signaling. Changes distinct metastable 'epigentically-fixed' states were measured by correlation protein, phosphoprotein, phosphopeptide RNA transcript abundance. The assembly 1167 modulated components into functional systems or machines simplified...
Epidermal growth factor receptor (EGFR) and insulin-like factor-I (IGF-IR) can cooperate to regulate tumor survival, synergistic inhibition has been reported for combined blockade of EGFR IGF-IR. However, in preclinical models, only a subset tumors exhibit high sensitivity this combination, highlighting the potential need patient selection optimize clinical efficacy. Herein, we have characterized molecular basis cooperative upon dual IGF-IR provide biomarkers that seem differentiate...
NSCLC cells with a mesenchymal phenotype have shown marked reduction in sensitivity to EGFR inhibitors, though the molecular rationale has remained obscure. Here we find that mesenchymal-like tumor both tyrosine phosphorylation of EGFR, ErbB2, and ErbB3 signaling networks expression family ligands were decreased. While chronic activation can promote an EMT-like transition, once having occurred was attenuated. We investigated mechanisms by which bypass acquire alternative routes proliferative...
Mammalian proteasomes are composed of 14–17 different types subunits, some which, including major-histocompatibility-complex-encoded subunits LMP2 and LMP7, non-essential present in variable amounts. We have investigated the distribution total individual rat liver by quantitative immunoblot analysis purified subcellular fractions (nuclei, mitochondria, microsomes cytosol). Proteasomes were mainly found cytosol but also nuclear microsomal fractions. In nuclei, soluble or loosely attached to...
ERK and p38 MAP kinases, acting through the downstream mitogen- stress-activated kinase 1/2 (MSK1/2), elicit histone H3 phosphorylation on a subfraction of nucleosomes – including those at Fos Jun concomitant with gene induction. S10 S28 tail have both been shown to be phospho-acceptors in vivo. Both phospho-epitopes appear similar time-courses occur tails that are highly sensitive TSA-induced hyperacetylation, similarities which might suggest MSK1/2 phosphorylates sites same tails. Indeed,...
Objectives Human serum paraoxonase (PON1) hydrolyses organophosphate pesticides (OPs) entering the blood circulation and tissue fluid thus limiting toxicity. The PON1 coding region has two polymorphisms involving amino acids at position 55 (Lt←M) 192 (Qt←R), giving rise to isoenzymes which differ in their catalytic rate for hydrolysis of OPs. We therefore hypothesized that individuals inheriting low activity isoforms would be more liable report symptoms OP Methods have investigated...
Metastasis is the major cause of death in cancer patients, yet genetic and epigenetic programs that drive metastasis are poorly understood. Here, we report an reprogramming pathway required for breast metastasis. Concerted differential DNA methylation initiated by activation RON receptor tyrosine kinase its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression G:T mismatch-specific thymine glycosylase MBD4. MBD4-dependent aberrant results...
Abstract Nature has evolved a vast array of strategies for propulsion at the air-fluid interface. Inspired by survival mechanism initiated honeybee ( Apis mellifera ) trapped on surface water, we here present SurferBot : centimeter-scale vibrating robotic device that self-propels fluid using analogous hydrodynamic mechanisms as stricken honeybee. This low-cost and easily assembled is capable rectilinear motion thanks to forces arising from wave-generated, unbalanced momentum flux, achieving...
Abstract When a solid body floats at the interface of vibrating liquid bath, motion object generates outwardly propagating surface waves. We here demonstrate that chiral objects on fluid are set into steady rotation, with angular speed and direction rotation controlled by interplay between geometry driving parameters. Scaling laws simplified model wavefield reveal underlying physical mechanism while collapsing measurements velocity across Leveraging control over object’s we an asymmetric...