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Role Of The Novel TGF-b Superfamily Cytokine MIC-1 In The Pathogenesis And Treatment Of Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$309,536.00
Summary
Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important family of proteins that are involved in wound healing, development and inflammation. Our data thus far suggests that MIC-1 is an anti-inflammatory factor that is of particular relevance in rheumatoid arthritis. We wish to determine the relationship between the amount of this cytokine in the ....Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important family of proteins that are involved in wound healing, development and inflammation. Our data thus far suggests that MIC-1 is an anti-inflammatory factor that is of particular relevance in rheumatoid arthritis. We wish to determine the relationship between the amount of this cytokine in the joint and the blood and the activity of rheumatoid arthritis. To better understand the actions of this molecule, we also want to study the factors that regulate the production of MIC-1 from human blood cells. Finally, to assess whether MIC-1 is useful for the treatment of rheumatoid arthritis, we will use gene therapy approaches to develop animals that produce increased amounts of MIC-1 and determine whether this prevents or mitigates the development of rheumatoid arthritis.Read moreRead less
The In Vivo Biology Of The Novel TGF-b Superfamily Cytokine, MIC-1
Funder
National Health and Medical Research Council
Funding Amount
$280,430.00
Summary
Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important familty of proteins that are involved in wound healing, development and inflammation. Our data thus far suggest thatMIC-1 is an antiinflammatory factor that also involved in reproduction, especially in the health of the placenta. To determine the accuracy of these predictions we wish to use ....Cytokines are hormone like messengers that mediate the interactions between cells. We have discovered a new cytokine that we have named macrophage inhibitory cytokine 1 (MIC-1). It belongs to a very important familty of proteins that are involved in wound healing, development and inflammation. Our data thus far suggest thatMIC-1 is an antiinflammatory factor that also involved in reproduction, especially in the health of the placenta. To determine the accuracy of these predictions we wish to use genetic techniques to delete this gene from a mouse. Study of this genetically modified mouse will give us a great deal of information on the most important roles of MIC-1.Read moreRead less
We discovered, characterised and commercialised Macrophage inhibitory cytokine-1 (MIC-1/GDF15) for human therapy. Its blood level predicts death from cancer, heart attack/stroke and other diseases. This study will add important information for understandg the actions of this important protein
The Role Of The TGF-b Superfamily Cytokine MIC-1 In Prostate Cancer Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
We have discovered that a protein called MIC-1 is strongly linked to prostate cancer and is made in large amounts by this tumor. There is a lot of circumstantial evidence that it is involved in the prostate cancer but the proof is missing. We propose to breed mice that are both prostate cancer prone and have genetically modified MIC-1 : mice either are unable to make MIC-1 , or make it in large amounts. We will determine how MIC-1 affects prostate cancer development.
Development Of A Humanised Antibody To MIC-1/GDF15 For Therapy Of Anorexia/cachexia Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$587,349.00
Summary
Severe starvation and weight loss (cachexia) is a complication that affects about one quarter of cancer patients. In many this is due to the cancer producing a powerfula appetite suppressive protein called MIC-1/GDF15. This weight loss can be prevented by blocking the protein with an antibody drug. We have already shown that we can treat mice in this way by using a mouse antibody. We now aim to engineer these antibodies by making them more human-like. This will allow us to treat weight loss in h ....Severe starvation and weight loss (cachexia) is a complication that affects about one quarter of cancer patients. In many this is due to the cancer producing a powerfula appetite suppressive protein called MIC-1/GDF15. This weight loss can be prevented by blocking the protein with an antibody drug. We have already shown that we can treat mice in this way by using a mouse antibody. We now aim to engineer these antibodies by making them more human-like. This will allow us to treat weight loss in human cancer patients.Read moreRead less
Cancer Anorexia/cachexia: Mechanisms For Anorexia And Appetite Regulation By Tumour Derived MIC-1/GDF15
Funder
National Health and Medical Research Council
Funding Amount
$643,060.00
Summary
We have recently discovered that MIC-1 is a new appetite suppressive agent which when overproduced in some diseases like cancer, causes severe weight loss. This project sets out to determine the mechanisms it employs in regulation of appetite centres in the brain.
The Role Of The TGF-b Superfamily Cytokine MIC-1 In The Pathogenesis Of Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$348,950.00
Summary
MIC-1 is a protein first cloned and characterised by our research group. It belongs to the TGF beta protein superfamily which is very important in development, cancer, wound - fracture healing and inflammation. The aim of this project was to start to gain an understanding of the role of this protein, both in normal biological processes (especially pregnancy) and in disease. MIC-1 is present in the blood of all individuals and high levels are associated with an increased risk of heart attacks and ....MIC-1 is a protein first cloned and characterised by our research group. It belongs to the TGF beta protein superfamily which is very important in development, cancer, wound - fracture healing and inflammation. The aim of this project was to start to gain an understanding of the role of this protein, both in normal biological processes (especially pregnancy) and in disease. MIC-1 is present in the blood of all individuals and high levels are associated with an increased risk of heart attacks and strokes. In this study we wish to use animal models, in which the gene for MIC-1 has either been deleted or enhanced, to determine whether MIIC-1 plays a direct role in these diseases.Read moreRead less
MODULATING MIC-1 CYTOKINE BIOAVAILABILITY: IMPACT ON TUMOUR BIOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$341,210.00
Summary
MIC-1 cytokine is secreted by many tumour cells. It is commonly secreted as an inactive precursor form of MIC-1 which binds to the extracellular matrix surrounding cells, via its propeptide. This creates latent stores of cytokine which can be released and activated under specific conditions. The propeptide controls the balance between latent stores of inactive MIC-1 precursor and soluble forms of mature bioactive cytokine, which can act on surrounding cells or move into the circulation. The sign ....MIC-1 cytokine is secreted by many tumour cells. It is commonly secreted as an inactive precursor form of MIC-1 which binds to the extracellular matrix surrounding cells, via its propeptide. This creates latent stores of cytokine which can be released and activated under specific conditions. The propeptide controls the balance between latent stores of inactive MIC-1 precursor and soluble forms of mature bioactive cytokine, which can act on surrounding cells or move into the circulation. The significance of these latent stores is underscored by the finding that the level of these stores correlates with prostate cancer outcome, and also that very high circulating levels of active MIC-1 cytokine in the blood, leads to the massive weight loss characteristic of a syndrome called cancer cachexia. This is common in late stages of cancer and is a major contributing factor to the death of cancer patients. Understanding the mechanisms by which latent MIC-1 stromal stores are created and regulated, as well as their role in tumourigenesis, will have major impact on our understanding of the role of this cytokine in cancer. This is essential in order to adequately harness that knowledge for the benefit of patients.Read moreRead less
Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15), CCAAT/enhancer Binding Protein Delta (CEBPD) And Neuroinflammtion
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
I will develop new therapies for multiple sclerosis and spinal cord injury. I will also evaluate diagnostic and therapeutic uses for macrophage inhibitory cytokine-1 (MIC-1/GDF15) that was discovered in Australia. I will confirm its use in screening for bowel cancer. Also, I will look at using it in the indigenous and wider Australian community to improve health and close the gap in life expectancy. Finally, I will conduct trials of MIC-1/GDF15 therapy of obesity and inflammation.