COLORECTAL CANCER - MOLECULAR BASIS TO TARGETED THERAPEUTICS
Grant number: 487922 | Funding period: 2012 - 2013
Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal cancer (CRC) and more than one third of people will die of their disease. CRC is caused by mistakes in production of colon cells. Our research aims to discover new ways to detect CRC, develop smart drugs and nanoparticle delivery systems for destroying all types of CRC cells. We will then test our new anti-cancer drugs in clinical trials with CRC patients.
Related publications (39)
TGF-beta and IL-6 family signalling crosstalk: an integrated model
Shabnam Khatibi, Jeff Babon, John Wagner, Jonathan H Manton, Chin Wee Tan, Hong-Jian Zhu, Sam Wormald, Antony W Burgess
Mathematical models for TGF-β and IL-6 signalling have been linked, providing a platform for analyzing the crosstalk between the s..
Intestinal-specific activatable Myb initiates colon tumorigenesis in mice
J Malaterre, L Pereira, T Putoczki, R Millen, S Paquet-Fifield, M Germann, J Liu, D Cheasley, S Sampurno, SA Stacker, MG Achen, RL Ward, P Waring, T Mantamadiotis, M Ernst, RG Ramsay
Transcription factor Myb is overexpressed in most colorectal cancers (CRC). Patients with CRC expressing the highest Myb are more ..
Frizzled7 Functions as a Wnt Receptor in Intestinal Epithelial Lgr5( ) Stem Cells
Dustin J Flanagan, Toby J Phesse, Nick Barker, Renate HM Schwab, Nancy Amin, Jordane Malaterre, Daniel E Stange, Cameron J Nowell, Scott A Currie, Jarel TS Saw, Eva Beuchert, Robert G Ramsay, Owen J Sansom, Matthias Ernst, Hans Clevers, Elizabeth Vincan
The mammalian adult small intestinal epithelium is a rapidly self-renewing tissue that is maintained by a pool of cycling stem cel..
MYB Elongation Is Regulated by the Nucleic Acid Binding of NF kappa B p50 to the Intronic Stem-Loop Region
Lloyd A Pereira, Honor J Hugo, Jordane Malaterre, Huiling Xu, Secondo Sonza, Alina Cures, Damian FJ Purcell, Paul A Ramsland, Steven Gerondakis, Thomas J Gonda, Robert G Ramsay
MYB transcriptional elongation is regulated by an attenuator sequence within intron 1 that has been proposed to encode a RNA stem ..
Particle generation, functionalization and sortase A-mediated modification with targeting of single-chain antibodies for diagnostic and therapeutic use
Christoph E Hagemeyer, Karen Alt, Angus PR Johnston, Georgina K Such, Hang T Ta, Melissa KM Leung, Sandeep Prabhu, Xiaowei Wang, Frank Caruso, Karlheinz Peter
Antibody fusion to nonprotein materials such as contrast agents or radio-tracers, nano- or microparticles or small-molecule drugs ..
Therapeutic DNA vaccination against colorectal cancer by targeting the MYB oncoprotein
Ryan S Cross, Jordane Malaterre, Alexander J Davenport, Sandra Carpinteri, Robin L Anderson, Phillip K Darcy, Robert G Ramsay
Cancers can be addicted to continued and relatively high expression of nuclear oncoproteins. This is evident in colorectal cancer ..
Tripartite interactions between Wnt signaling, Notch and Myb for stem/progenitor cell functions during intestinal tumorigenesis
Markus Germann, Huiling Xu, Jordane Malaterre, Shienny Sampurno, Mathilde Huyghe, Dane Cheasley, Silvia Fre, Robert G Ramsay
Deletion studies confirm Wnt, Notch and Myb transcriptional pathway engagement in intestinal tumorigenesis. Nevertheless, their co..
Partial inhibition of gp130-Jak-Stat3 signaling prevents Wnt-beta-catenin-mediated intestinal tumor growth and regeneration
Toby J Phesse, Michael Buchert, Emma Stuart, Dustin J Flanagan, Maree Faux, Shoukat Afshar-Sterle, Francesca Walker, Hui-Hua Zhang, Cameron J Nowell, Robert Jorissen, Chin Wee Tan, Yumiko Hirokawa, Moritz F Eissmann, Ashleigh R Poh, Jordane Malaterre, Helen B Pearson, David G Kirsch, Paolo Provero, Valeria Poli, Robert G Ramsay
Most colon cancers arise from somatic mutations in the tumor suppressor gene APC (adenomatous polyposis coli), and these mutations..
Physiological expression of the PI3K-activating mutation Pik3ca(H1047R) combines with Apc loss to promote development of invasive intestinal adenocarcinomas in mice
Lauren M Hare, Toby J Phesse, Paul M Waring, Karen G Montgomery, Kathryn M Kinross, Kevin Mills, Vincent Roh, Joan K Heath, Robert G Ramsay, Matthias Ernst, Wayne A Phillips
PIK3CA, the gene encoding the p110α catalytic subunit of PI3K (phosphoinositide 3-kinase), is mutated in approximately 20% of spor..
Differential Roles of the Protein Corona in the Cellular Uptake of Nanoporous Polymer Particles by Monocyte and Macrophage Cell Lines
Yan Yan, Katelyn T Gause, Marloes MJ Kamphuis, Ching-Seng Ang, Neil M O'Brien-Simpson, Jason C Lenzo, Eric C Reynolds, Edouard C Nice, Frank Caruso
Many biomolecules, mainly proteins, adsorb onto polymer particles to form a dynamic protein corona in biological environments. The..
Particles on the Move: Intracellular Trafficking and Asymmetric Mitotic Partitioning of Nanoporous Polymer Particles
Yan Yan, Zon W Lai, Robert JA Goode, Jiwei Cui, Tess Bacic, Marloes MJ Kamphuis, Edouard C Nice, Frank Caruso
Nanoporous polymer particles (NPPs) prepared by mesoporous silica templating show promise as a new class of versatile drug/gene de..
The Myb-p300-CREB axis modulates intestine homeostasis, radiosensitivity and tumorigenesis
S Sampurno, A Bijenhof, D Cheasley, H Xu, S Robine, D Hilton, WS Alexander, L Pereira, T Mantamadiotis, J Malaterre, RG Ramsay
The gastrointestinal (GI) epithelium is constantly renewing, depending upon the intestinal stem cells (ISC) regulated by a spectru..
The CSF-1 receptor fashions the intestinal stem cell niche
Dilara Akcora, Duy Huynh, Sally Lightowler, Markus Germann, Sylvie Robine, Jan R de May, Jeffrey W Pollard, E Richard Stanley, Jordane Malaterre, Robert G Ramsay
Gastrointestinal (GI) homeostasis requires the action of multiple pathways. There is some controversy regarding whether small inte..
CSF-1 Receptor-Dependent Colon Development, Homeostasis and Inflammatory Stress Response
Huynh Duy, Dilara Akcora, Jordane Malaterre, Chee Kai Chan, Xu-Ming Dai, Ivan Bertoncello, E Richard Stanley, Robert G Ramsay
The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) directly regulates the development of Paneth cells (PC) and influences p..
Direct repression of MYB by ZEB1 suppresses proliferation and epithelial gene expression during epithelial-to-mesenchymal transition of breast cancer cells
Honor J Hugo, Lloyd Pereira, Randy Suryadinata, Yvette Drabsch, Thomas J Gonda, NPA Devika Gunasinghe, Cletus Pinto, Eliza TL Soo, Bryce JW van denderen, Prue Hill, Robert G Ramsay, Boris Sarcevic, Donald F Newgreen, Erik W Thompson
INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) promotes cell migration and is important in metastasis. Cellular prolifer..
The tumor suppressor Apc controls planar cell polarities central to gut homeostasis
Julien Bellis, Isabelle Duluc, Beatrice Romagnolo, Christine Perret, Maree C Faux, Denis Dujardin, Caroline Formstone, Sally Lightowler, Robert G Ramsay, Jean-Noel Freund, Jan R De Mey
The stem cells (SCs) at the bottom of intestinal crypts tightly contact niche-supporting cells and fuel the extraordinary tissue r..
Estrogen receptor-alpha recruits P-TEFb to overcome transcriptional pausing in intron 1 of the MYB gene
Partha Mitra, Lloyd A Pereira, Yvette Drabsch, Robert G Ramsay, Thomas J Gonda
The MYB proto-oncogene is expressed in most estrogen receptor-positive (ERα(+)) breast tumors and cell lines. Expression of MYB is..
RAD21 Mutations Cause a Human Cohesinopathy
Matthew A Deardorff, Jonathan J Wilde, Melanie Albrecht, Emma Dickinson, Stephanie Tennstedt, Diana Braunholz, Maren Moennich, Yuqian Yan, Weizhen Xu, Maria Concepcion Gil-Rodriguez, Dinah Clark, Hakon Hakonarson, Sara Halbach, Laura Daniela Michelis, Abhinav Rampuria, Eva Rossier, Stephanie Spranger, Lionel Van Maldergem, Sally Ann Lynch, Gabriele Gillessen-Kaesbach
The evolutionarily conserved cohesin complex was originally described for its role in regulating sister-chromatid cohesion during ..
Enhanced Lithium-Induced Brain Recovery Following Cranial Irradiation Is Not Impeded by Inflammation
Jordane Malaterre, Cameron S McPherson, Delphine Denoyer, Emily Lai, Jim Hagekyriakou, Sally Lightowler, Koishi Shudo, Matthias Ernst, David M Ashley, Jennifer L Short, Greg Wheeler, Robert G Ramsay
Radiation-induced brain injury occurs in many patients receiving cranial radiation therapy, and these deleterious effects are most..
Macromolecule Functionalization of Disulfide-Bonded Polymer Hydrogel Capsules and Cancer Cell Targeting
Olga Shimoni, Almar Postma, Yan Yan, Andrew M Scott, Joan K Heath, Edouard C Nice, Alexander N Zelikin, Frank Caruso
We present a generic and versatile method for functionalization of disulfide-stabilized PMA hydrogel capsules (HCs) with macromole..
Bio-Click Chemistry: Enzymatic Functionalization of PEGylated Capsules for Targeting Applications
Melissa KM Leung, Christoph E Hagemeyer, Angus PR Johnston, Catalina Gonzales, Marloes MJ Kamphuis, Katie Ardipradja, Georgina K Such, Karlheinz Peter, Frank Caruso
All sorted: The enzyme Sortase A was used to catalyze functionalization of PEGylated capsules with an activation-specific anti-pla..
Cellular Association and Cargo Release of Redox-Responsive Polymer Capsules Mediated by Exofacial Thiols
Yan Yan, Yajun Wang, Joan K Heath, Edouard C Nice, Frank Caruso
Redox-responsive polymer capsules stabilized by disulfide bonds and loaded with hydrophobic cargo are prepared by templating mesop..
Colony-Stimulating Factor-1 Promotes Kidney Growth and Repair via Alteration of Macrophage Responses
Maliha A Alikhan, Christina V Jones, Timothy M Williams, Anthony G Beckhouse, Anne L Fletcher, Michelle M Kett, Samy Sakkal, Chrishan S Samuel, Robert G Ramsay, James A Deane, Christine A Wells, Melissa H Little, David A Hume, Sharon D Ricardo
Colony-stimulating factor (CSF)-1 controls the survival, proliferation, and differentiation of macrophages, which are recognized a..
Polymersome-Loaded Capsules for Controlled Release of DNA
Hannah Lomas, Angus PR Johnston, Georgina K Such, Zhiyuan Zhu, Kang Liang, Martin P van Koeverden, Siripong Alongkornchotikul, Frank Caruso
The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer cap..
PHLDA1 Expression Marks the Putative Epithelial Stem Cells and Contributes to Intestinal Tumorigenesis
Anuratha Sakthianandeswaren, Michael Christie, Carla D'Andreti, Cary Tsui, Robert N Jorissen, Shan Li, Nicholas I Fleming, Peter Gibbs, Lara Lipton, Jordane Malaterre, Robert G Ramsay, Toby J Phesse, Matthias Ernst, Rosemary E Jeffery, Richard Poulsom, Simon J Leedham, Stefania Segditsas, Ian PM Tomlinson, Oliver K Bernhard, Richard J Simpson
Studies employing mouse models have identified crypt base and position +4 cells as strong candidates for intestinal epithelial ste..
Bypassing Multidrug Resistance in Cancer Cells with Biodegradable Polymer Capsules
Yan Yan, Christopher J Ochs, Georgina K Such, Joan K Heath, Edouard C Nice, Frank Caruso
Biodegradable polymer capsules with drug-loaded multilayers were prepared through click chemistry via layer-by-layer assembly. The..
Targeting of Cancer Cells Using Click-Functionalized Polymer Capsules
Marloes MJ Kamphuis, Angus PR Johnston, Georgina K Such, Henk H Dam, Richard A Evans, Andrew M Scott, Edouard C Nice, Joan K Heath, Frank Caruso
Targeted delivery of drugs to specific cells allows a high therapeutic dose to be delivered to the target site with minimal harmfu..
Encapsulation of Water-Insoluble Drugs in Polymer Capsules Prepared Using Mesoporous Silica Templates for Intracellular Drug Delivery
Yajun Wang, Yan Yan, Jiwei Cui, Leticia Hosta-Rigau, Joan K Heath, Edouard C Nice, Frank Caruso
Water-insoluble compounds were encapsulated in polymer capsules through mesoporous silica nanoparticle-mediated layer-by-layer ass..
Uptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells
Yan Yan, Angus PR Johnston, Sarah J Dodds, Marloes MJ Kamphuis, Charles Ferguson, Robert G Parton, Edouard C Nice, Joan K Heath, Frank Caruso
Understanding the interactions between drug carriers and cells is of importance to enhance the delivery of therapeutics. The relea..