A5022119524- Cellular Mechanics and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Cell death mechanisms and regulation
- Melanoma and MAPK Pathways
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Fibroblast Growth Factor Research
- Hippo pathway signaling and YAP/TAZ
- Phagocytosis and Immune Regulation
- Cancer Treatment and Pharmacology
- Cardiomyopathy and Myosin Studies
- Cellular transport and secretion
- Immune cells in cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Pancreatic and Hepatic Oncology Research
- Kruppel-like factors research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Wnt/β-catenin signaling in development and cancer
Toronto Metropolitan University
2015-2025
University of Toronto
1991-2024
Snow College
2024
University of Chicago
2024
Cancer Research UK Scotland Institute
2012-2023
Cancer Research UK
2002-2023
University of Glasgow
2011-2023
Baylor College of Medicine
2022-2023
California Air Resources Board
2022
MaRS
2020-2022
Members of the Rho family small guanosine triphosphatases (GTPases) regulate organization actin cytoskeleton; controls assembly stress fibers and focal adhesion complexes, Rac regulates filament accumulation at plasma membrane to produce lamellipodia ruffles, Cdc42 stimulates formation filopodia. When microinjected into quiescent fibroblasts, Rho, Rac, stimulated cell cycle progression through G1 subsequent DNA synthesis. Furthermore, microinjection dominant negative forms or inhibitor C3...
Receptor tyrosine kinase-mediated activation of the Raf-1 protein kinase is coupled to small guanosine triphosphate (GTP)-binding Ras. By contrast, C (PKC)-mediated thought be Ras independent. Nevertheless, stimulation PKC in COS cells led and formation Ras-Raf-1 complexes containing active Raf-1. mutations that prevent its association with blocked by PKC. However, was not dominant negative Ras, indicating activates a mechanism distinct from initiated receptor kinases.
The chemokine receptor CXCR2 is a key mediator of neutrophil migration that also plays role in tumor development. However, influences tumors through multiple mechanisms and might promote or inhibit development depending on context. Here, we used several mouse models spontaneous inflammation-driven neoplasia to define indispensable roles for benign malignant tumors. CXCR2-activating chemokines were part the secretome cultured primary intestinal adenomas (ApcMin/+) highly expressed by all...
Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that activity, myosin light chain (MLC) phosphorylation, MLC ATPase an intact actin cytoskeleton, but not microtubular are required for disruption nuclear integrity apoptosis. Inhibition or which protect integrity, does affect degradation proteins such as lamins A, B1, C. The conditional I was sufficient to tear apart nuclei in lamin A/C null fibroblasts,...
Apoptosis is a fundamental homeostatic mechanism essential for the normal growth, development and maintenance of every tissue organ. Dying cells have been defined as apoptotic by distinguishing features, including cell contraction, nuclear fragmentation, blebbing, body formation intact cellular membranes to prevent massive protein release consequent inflammation. We now show that during early apoptosis limited membrane permeabilization occurs in blebs bodies, which allows proteins may affect...
LIM kinases 1 and 2 (LIMK1/2) are centrally positioned regulators of actin cytoskeleton dynamics. Using siRNA-mediated knockdown or a novel small molecule inhibitor, we show LIMK is required for path generation by leading tumor cells nontumor stromal during collective cell invasion. inhibition lowers cofilin phosphorylation, F-actin levels, serum response factor transcriptional activity collagen contraction, reduces invasion in three-dimensional assays. Although motility was unaffected,...
The ability to observe changes in molecular behavior during cancer cell invasion vivo remains a major challenge our understanding of the metastatic process. Here, we demonstrate for first time, an analysis RhoA activity at subcellular level using FLIM-FRET (fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer) live animal model pancreatic cancer. In invasive mouse ductal adenocarcinoma (PDAC) cells driven by mutant p53 (p53(R172H)), observed discrete fraction high...
Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death; identifying PDAC enablers may reveal potential therapeutic targets. Expression the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression patients, or conditional activation Kras
Abstract Progression of tumors to invasive and metastatic forms requires that tumor cells undergo dramatic morphologic changes, a process regulated by Rho GTPases. Elevated expression RhoA RhoC, as well the effector proteins ROCK I II, are commonly observed in human cancers often associated with more phenotypes. To examine how contributes progression solid tumors, we established conditionally activated form II fusing kinase domain estrogen receptor hormone-binding (ROCK:ER)....
The lbc oncogene is tumorigenic in nude mice, transforms NIH 3T3 fibroblasts, and encodes a Dbl homology domain found several transforming gene products including the dbl product. While both lbc- dbl-transformed foci exhibited comparable gross appearance, lbc-transformed cell morphology was clearly distinct from that of cells. Given these differences, we investigated biochemical activity target specificity Lbc oncoprotein vivo vitro. Here show associates specifically with GTP-binding protein...