The Role Of Secretory Antibodies In Mucosal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of th ....This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of the mucosal tissues, to prevent recognition of this material by the immune system. Such recognition could result in serious consequences both locally (ie. in the gut) and more distally eg. in the pnacreas leading to diabetes. As a consequence, we believe that these antibodies are fundamental to health. The research could have important ramifications for diseases resulting from immune responses against host tissues, so-called autoimmune diseases like diabetes.Read moreRead less
CD44v3 And V6 As Targets For Anti-metastasis Therapy
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Cancer metastasis remains the principal cause of treatment failure in malignant disease. Current therapies for metastases are generally non-specific, and can cause considerable systemic toxicity. The ideal target for metastasis therapy would be expressed by a broad range of tumours, but be restricted in expression in normal tissues. CD44 is a family of widely expressed cell-surface adhesion molecules and its members are implicated in a variety of physiological and pathological processes, includi ....Cancer metastasis remains the principal cause of treatment failure in malignant disease. Current therapies for metastases are generally non-specific, and can cause considerable systemic toxicity. The ideal target for metastasis therapy would be expressed by a broad range of tumours, but be restricted in expression in normal tissues. CD44 is a family of widely expressed cell-surface adhesion molecules and its members are implicated in a variety of physiological and pathological processes, including tumour progression and metastasis. CD44 has considerable molecular diversity and its broad range of known biological activities suggests that multiple domains in the molecule may confer different biological functions. The core CD44 molecule, termed CD44s, is the most commonly expressed CD44 molecule. CD44 variants (termed CD44v) are much more restricted in their expression in normal tissues, and hence may make specific targets for anti-metastasis therapy. We have shown that CD44 variants are expressed by colorectal tumours from the earliest stages of tumour development, and that theses variants are found to be expressed by colorectal hepatic metastases. We targeted two key domains in the variants and found that by inhibiting expression in these domains we showed complete abrogation of metastasis, and of primary tumour growth in mice. Hence these domains in the CD44 molecule are directly involved in cancer spread. We propose to develop a number of specific methods of targeting CD44 in order to prevent the spread of cancer. We have and will develop additional agents directed to these key domains in CD44. Targeting these domains has great potential as metastasis therapy.Read moreRead less