A5021719937- Cellular Mechanics and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Cell Adhesion Molecules Research
- Hippo pathway signaling and YAP/TAZ
- Protease and Inhibitor Mechanisms
- Melanoma and MAPK Pathways
- Liver physiology and pathology
- Bacillus and Francisella bacterial research
- Wnt/β-catenin signaling in development and cancer
- Pancreatic and Hepatic Oncology Research
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Advanced Fluorescence Microscopy Techniques
- RNA Interference and Gene Delivery
- Microtubule and mitosis dynamics
- Insect and Pesticide Research
- Cancer Genomics and Diagnostics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Prostate Cancer Treatment and Research
- Insect Resistance and Genetics
- Ubiquitin and proteasome pathways
- Molecular Junctions and Nanostructures
- Advanced Electron Microscopy Techniques and Applications
- Caveolin-1 and cellular processes
- Epigenetics and DNA Methylation
University of Calgary
2025
King's College London
2014-2024
University of Memphis
2019
The University of Tokyo
2017
Scripps Research Institute
2017
Huntsman (United States)
2010-2017
King's College - North Carolina
2017
University of North Carolina at Chapel Hill
2017
University of Illinois Chicago
2017
Guy's Hospital
2015
Rac GTPases are believed to contribute migration in leukocytes by transducing signals from cell surface receptors the actin and microtubule cytoskeletons. Mammals have three closely related isoforms, Rac1, Rac2 Rac3, it is widely assumed that requires activity of these GTPases. We previously shown Rac1-null mouse macrophages altered shape reduced membrane ruffling but normal speed. Here we investigate behaviour lacking (Rac2–/–) or Rac1 (Rac1/2–/–). Rac2–/– F-actin levels lack podosomes,...
Rac GTPases are activated by extracellular stimuli and contribute to cellular responses including cytoskeletal changes cell migration. Dominant-negative Rac1 has been used implicate in these responses, but which of the three mammalian isoforms it inhibits is not known. We show that mouse bone marrow-derived macrophages express Rac1, low levels Rac2 Rac3. As Rac1-null mice die early development, we have with a loxP-flanked allele type I interferon-inducible Mx1-Cre transgene address for first...
We investigated the myosin expression profile in prostate cancer cell lines and found that Myo1b, Myo9b, Myo10, Myo18a were expressed at higher levels cells with high metastatic potential. Moreover, Myo1b Myo10 tumors. Using an siRNA-based approach, we knockdown of each resulted distinct phenotypes. ablated filopodia decreased 2D migration speed. increased circumferential non-muscle 2A-associated actin filament arrays lamella reduced directional persistence migration. Myo9b stress fiber...
Hepatocyte growth factor (HGF) is associated with tumour progression and increases the invasiveness of prostate carcinoma cells. Migration invasion require coordinated reorganisation actin cytoskeleton regulation cell-adhesion dynamics. Rho-family GTPases orchestrate both these cellular processes. p21-activated kinase 4 (PAK4), a specific effector Rho GTPase Cdc42, activated by HGF, we have previously shown that PAK4 induces loss stress fibres focal adhesions. We now report DU145 human...
Potassium ion channels are critical in the regulation of cell motility. The acquisition motility is an essential parameter cancer metastasis. However, role K+ metastasis has been poorly studied. High expression hG1 gene, which encodes for Kv11.1 channel associates with good prognosis estrogen receptor-negative breast (BC). We evaluated efficacy activator NS1643 arresting a triple negative (TNBC) mouse model. significantly reduces metastatic spread tumors vivo by inhibiting motility,...
P21-activated kinase 4 (PAK4) is a Cdc42 effector protein thought to regulate cell adhesion disassembly in kinase-dependent manner. We found that PAK4 expression significantly higher high-grade human breast cancer patient samples, whereas depletion of modifies dynamics cells. Surprisingly, systematic analysis functionality revealed PAK4-driven turnover neither dependent on binding nor activity. Rather, reduced leads concomitant loss RhoU expression. report targeted for ubiquitination by the...
Abstract During their metastatic spread, cancer cells need to remodel the extracellular matrix in order migrate through stromal compartments adjacent primary tumor. Dissemination of breast carcinoma is mediated by membrane type 1-matrix metalloproteinase (MT1-MMP/MMP14), main invadopodial degradative component. Here, we identify MT1-MMP as a novel interacting partner dual-specificity LIM Kinase-1 and -2 (LIMK1/2) provide several evidence for phosphorylation tyrosine Y573 cytoplasmic domain...
The p21-activated kinases (PAKs) are divided into two subgroups based on sequence homology. Group 1 PAKs (PAK1-3) involved in cell migration, and activated by pro-migratory stimuli Cdc42/Rac GTPases. In contrast, little is known about the regulation of recently identified group II (PAK4-6). Here we report that PAK4 HGF, a migratory stimulus for epithelial cells. unstimulated MDCK cells, induces decrease stress fibres, when cells stimulated with it loss focal complexes rounding. This response...
ERK3 is an atypical Mitogen-activated protein kinase (MAPK6). Despite the fact that Erk3 gene was originally identified in 1991, its function still unknown. MK5 (MAP kinase- activated 5) also called PRAK only known substrate for ERK3. Recently, it found group I p21 kinases (PAKs) are critical effectors of PAKs link Rho family GTPases to actin cytoskeletal dynamics and be involved regulation cell adhesion migration. In this study we demonstrate levels elevated as MDA-MB-231 breast cancer...
Abstract Fatty acid synthase (FASN) is commonly overexpressed in prostate cancer and associated with tumour progression. FASN responsible for de novo synthesis of the fatty palmitate; building block protein palmitoylation. Recent work has suggested that alongside its established role promoting cell proliferation may also promote invasion. We now find depletion expression increases adhesiveness, impairs HGF-mediated migration reduces 3D These changes motility suggest can mediate actin...
A hydrogen peroxide-based decontaminant, Decon Green, is efficacious for the decontamination of chemical agents VX (S-2-(diisopropylamino)ethyl O-ethyl methylphosphonothioate), GD (Soman, pinacolyl methylphosphonofluoridate), and HD (mustard, bis(2-chloroethyl) sulfide); biological agent anthrax (Bacillus anthracis); radiological isotopes 137Cs 60Co; thus demonstrating ability this approach to ameliorate aftermath all three types weapons mass destruction (WMD). Reaction mechanisms afforded...
Abstract It has been reported that p21-activated kinase 4 (PAK4) is amplified in pancreatic cancer tissue. PAK4 a member of the PAK family serine/threonine kinases, which act as effectors for several small GTPases, and specifically identified to function downstream HGF-mediated c-Met activation PI3K dependent manner. However, functionality contribution made by HGF signalling cell motility remain be elucidated. We now find elevated expression coincident with increased levels p85α subunit...
During tumour progression, oxygen tension in the microenvironment surrounding cells is reduced, resulting hypoxia. It well established that cancer resist negative effects of hypoxia by inducing angiogenesis predominantly via activity transcription factor hypoxia-inducible factor-1 (HIF-1). However, more recently HIF-1α has also been linked to increased invasive potential, although molecular mechanisms remain be defined. Invasive are thought employ membrane protrusions, termed invadopodia,...
Imaging the spatiotemporal interaction of proteins in vivo is essential to understanding complexities biological systems. The highest accuracy monitoring protein-protein interactions achieved using Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging, with measurements taking minutes acquire a single frame, limiting their use dynamic live cell We present diffraction limited, massively parallel, time-resolved multifocal multiphoton microscope capable producing...
// Helen Ross-Adams 1 , Stephen Ball 2 Kate Lawrenson 3 Silvia Halim Roslin Russell Claire Wells 4 Siri H. Strand 5 Torben F. Ørntoft Melissa Larson 6 Sebastian Armasu Charles E. Massie Mohammad Asim Martin M. Mortensen 8 Michael Borre Kathryn Woodfine Anne Y. Warren 9 Alastair D. Lamb 1,10 Jonathan Kay 1,15 Hayley Whitaker Antonio Ramos-Montoya Adele Murrell 7 Karina Sørensen Brooke L. Fridley 11 Ellen Goode Simon A. Gayther John Masters David Neal 1,10,* and Ian G. Mills...
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis because of its high propensity to metastasize and immunosuppressive microenvironment. Using panel pancreatic cancer cell lines, three-dimensional (3D) invasion systems, microarray gene signatures, microfluidic devices, mouse models, intravital imaging, we demonstrate that ROCK-Myosin II activity in PDAC cells supports transcriptional program conferring amoeboid invasive traits vivo metastatic abilities. Moreover, find immune...
To develop test methods and evaluate the survival of Bacillus anthracis ∆Sterne thuringiensis Al Hakam spores after exposure to hot, humid air.Spores (>7 logs) both strains were dried on six different materials. Response surface methodology was employed identify limits spore at optimal combinations temperature (60, 68, 77°C), relative humidity 75, 90%) time (1, 4, 7 days). No survived harshest run (77°C, 90% r.h., days), while > 6·5 logs mildest (60°C, 60% 1 day). Spores inoculated nylon...