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Gene therapeutic approach for studying fibrosis and blood vessel formation in the body
The main focus of this group is to understand the biology of bloodvessels and their role in tumor formation and fibrosis. Fibrosis is a common denominator in a wide variety of diseases characterized by chronic inflammation including stroma formation in solid tumors, rheumatoid arthritis and inflammatory bowel disease, connective tissue diseases, atherosclerosis, heart failure, transplant rejection and wound healing to name a few. The progression of fibrosis in these diseases leads to the derangement of tissue architecture and subsequent failure of the organ. In many of these diseases current therapeutic approaches have only marginally contributed to cure and must be seen as approaches that delay the progression of the disease. However, in certain circumstances in the adult, diseased organs (for instance the kidney in glomeruloid nephritis, the liver after hepatitis, and the heart during ventricular hypertrophia) are capable of healing themselves with minimal damage to the tissue and its function. Tissue regeneration following damage to an organ during embryogenesis and infancy is also an example of tissue repair with minimal functional sequel. In the adult, a pregnant women together with the fetus is able to create a new functional organ, namely the placenta. Thus, the adult body has mechanisms by which to adequately repair damaged organs and even create new organs. Why the body does not always achieve this, and what causes progression in one instance, and healing in another, is largely unknown and is one of the main subjects of study in the lab.
Several lines of investigation are currently being set up in the lab to address different aspects of the process of bloodvessel formation, fibrosis and tissue regeneration involving; gene therapy; microarray techniques combined with proteonomics; isolation of stem cells and how they are able to differentiate into collagen type I producing fibroblasts in the body and in the culture dish; low molecular weight drug therapy; and isolation of novel substances which may inhibit the development of fibrosis and tumor progression.
The second line of investigation is to study cell progression and events that occur during blood vessel formation and fibrosis in the body. To this effect gene therapy techniques will be used inorder to introduce genes for growth factors into normal and diseased tissues, both individually and in combination. Effects of these growth factors will be studied using advanced morphological and physiological techniques which are being developed. Previous studies by myself using this approach has lead to the discovery of three novel modes of angiogenesis including the creation of muscular arteries. This approach might be used for treatment of heart disease as well as diseases in other arteries in the body resulting from arteriosclerosis and diabetes. Furthermore, this technique will be used to complement the first line of investigation regarding stemcells and cell lineage progression.
This project is basically the following: We have a number of adenoviral constructs for gene therapeutic use. One of these constructs will be injected into animal skin. Tissues will be harvested and analyzed using advanced morphological techniques
This project I think would interest scientists whom want to learn about gene therapy, animal work, tissue processing and analysis.
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