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Isolation of compounds that inhibit fibrosis and tumor stroma formation and optimalization of drug delivery
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 fourth line of investigation is based on inhibiting fibrosis and targeting the non-endothelial compartment of the tumor stroma in solid tumors. We have found potential sources for these inhibitors. The rational is to treat diseases characterized by fibrosis by inhibiting the earliest stages of the fibrotic response. Conventional treatment of fibrosis, target collagen production which is a relatively late event in fibrotic disease. Furthermore, existing inhibitors will also be tested that target growth factor receptors in the above mentioned animal models. Small peptide inhibitors and drug delivery systems will also be part of this line of investigation with the goal of increasing treatment efficiency and improving the pharmacokinetics of experimental compounds.
This project is basically the following. We know which tumor cell lines and which compound/s stimulate production of this compound/s. Culture medium has been accumulated. The first step is to repeat previous results and make sure that we are able to inhibit fibrosis. The next step is to try and isolate this compound inorder to identify it. At our department we have the expertise inorder to expedite this project.
This project I think would interest scientists whom want to learn about cell biological techniques, proliferation and differentiation assays, and protein purification.
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