Role Of PAK1 In Colorectal Cancer Growth And Metastasis Regulated By Gastrins
Funder
National Health and Medical Research Council
Funding Amount
$460,070.00
Summary
Increased level of PAK1(a protein kinase) was associated with the progression of colorectal (large bowel) cancer (CRC). Gastrin peptides are growth factors responsible for CRC development. The objective of this project is to determine the role of PAK1 in the regulation of CRC growth and metastasis by gastrin peptides. We will use cell culture, animal models and clinical samples in the program. A successful outcome will lead to the development of new CRC therapies such as inhibitors of PAK1.
Tumour cells are often characterized by defects in signaling pathways. One of the most important signaling cascades involved in the development of cancer is the EGFR-Ras-MAPK pathway. EGFR is often overexpressed in breast cancer, leading to enhanced Ras signaling (hyperactive Ras) and cell transformation. The proposed project aims to identify the molecular mechanisms that can downregulate hyperactive Ras and will make a valuable contribution to our understanding of EGFR-Ras related cancers.
Fluorescence Analysis Of The EGFreceptor Signalling Network
Funder
National Health and Medical Research Council
Funding Amount
$490,750.00
Summary
Receptors are cell-surface molecules that enable the cell to receive chemical messages from the outside environment and transmit these signals to the inside of cell. These messages tell the cells to grow, divide or die. The Epidermal Growth Factor Receptor is linked to a variety of cell signalling pathways that are critical to the normal functioning of cells. Conversely, abberations in Epidermal Growth Factor-mediated cell signalling leads to many types of cancers. A basic understanding of how t ....Receptors are cell-surface molecules that enable the cell to receive chemical messages from the outside environment and transmit these signals to the inside of cell. These messages tell the cells to grow, divide or die. The Epidermal Growth Factor Receptor is linked to a variety of cell signalling pathways that are critical to the normal functioning of cells. Conversely, abberations in Epidermal Growth Factor-mediated cell signalling leads to many types of cancers. A basic understanding of how the receptor is turned off or on is essential to designing drugs that can specifically inhibit its hyperproliferative response. High resolution structures of a key part of the Epidermal Growth Factor Receptor have identified several structural forms of the receptor that are providing valuable clues as to the structural basis for receptor activation. Armed with this information and advanced microscopic imaging technology we are in the unique position to probe receptor activation in living cells. This project seeks to determine which structural form of the receptor is responsible for transmission of cellular messages and how it is impaired in cancerous cells.Read moreRead less
The focus of my research is mechanisms of growth factor receptor signal transduction and how they are altered in specific disease states, particularly cancer.
The regulated movement of membrane receptors and ligands between the cell surface and intracellular compartments is vital to many cellular operations, including communication between cells and their environment. However, the molecular details of these sorting events remain poorly defined. Determination of the mechanisms that control the cellular distribution of receptors is critical for understanding normal cellular processes and in pathological processes like tumorigenesis.
Elucidation of the hierarchy of stem, progenitor and mature cells in the mouse mammary gland. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last 30 years, many women still die from the disease. It is therefore important to identify new targets for breast cancer treatment. There is growing interest in the concept that a cancer-initiating cell may arise from a stem cell or progenitor cell in the mammary gland. O ....Elucidation of the hierarchy of stem, progenitor and mature cells in the mouse mammary gland. Breast cancer is the most common cause of cancer-related death in women in Australia. Although the treatments have improved over the last 30 years, many women still die from the disease. It is therefore important to identify new targets for breast cancer treatment. There is growing interest in the concept that a cancer-initiating cell may arise from a stem cell or progenitor cell in the mammary gland. Our goal is to identify those cells and to determine which genes are involved in transforming a normal cell to a cancerous cell.Read moreRead less
Regulated Shuttling Of Beta-catenin And IQGAP1 Between Nucleus And Plasma Membrane In Migrating Cells
Funder
National Health and Medical Research Council
Funding Amount
$511,703.00
Summary
Inherited gene mutations that cause colon cancer kill 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by age 75. Activation of the beta-catenin protein is a critical switch in the path to colon cancer. We discovered that beta-catenin, and another protein it interacts with called IQGAP1, move between different cellular compartments. We plan to study this process in more detail, as it relates to how beta-catenin works and to understanding its role in cancer.
Targeting Of The APC Tumour Suppressor To Mitochondria: Implications For APC Regulation And Cellular Function
Funder
National Health and Medical Research Council
Funding Amount
$390,116.00
Summary
Inherited mutations in the APC gene cause colon cancer, and kills 4,700 Australians every year. About 1 in 21 Australians develop colorectal cancer by the age of 75. APC mutations change cells in different ways, triggering the cancer process. We have discovered a new pathway, involving altered movement of APC to mitochondria in tumour cells. This study will investigate how this cancerous change may help our understanding of colon cancer progression.
Structural Basis Of Ligand Binding To Type 1 Insulin-like Growth Factor Receptor (IGF-1R)
Funder
National Health and Medical Research Council
Funding Amount
$446,562.00
Summary
Insulin-like growth factors are involved in normal growth and development. However, they are also implicated in cancer development and progression. We are seeking to understand the way in which these growth factors bind to their receptor on the surface of the cell and stimulate the cell to survive, proliferate and migrate to new tumour sites. Such knowledge will be useful in the design of molecules that could potentially intervere with this process and thus be used as anti-cancer therapeutics.