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The world is witnessing an unprecedented pace of medical discovery, aided in part by tremendous advances in genetics and proteomics that are ushering in a new generation of therapies. Dr. Matthias Clauss, a researcher at Indiana Center for Vascular Biology and Medicine and associate professor of cellular and integrative physiology at Indiana University School of Medicine, is on the cutting edge. Among other things, he is researching new methods to more accurately promote the growth of blood vessels (angiogenesis) to oxygen-starved heart muscle and conversely inhibit growth of blood vessels (anti-angiogenesis) to combat cancers. Dr. Clauss’ targeted vascular research will one day lead to the development of drugs tailored to treat diseases with fewer of the side effects common to many of today’s less targeted therapies. NHW spoke with Dr. Clauss to learn more about this exciting field of research.
NHW: Could you tell us about your research?
MC: The overall focus of my research is to treat dis-eases associated with blood vessels, which would include a wide range of therapies and diseases. My research focuses on the inner lining of blood vessels, which is called the endothelium.
NHW: What is vascular targeting, and how would it benefit patients?
MC: Vascular targeting can affect future patients on many levels. Vascular targeting exploits the fact that our blood vessels are under the influence of their environment--the tissue environment and the disease environment. For instance, blood vessels in the heart are not only different from the architecture of the blood vessels in the lung, but they are also different because cardiomyocytes--heart muscle cells--emit different signals to blood vessels than, for example, epithelial lung cells. We have tissue-specific differences.
One novel concept is to identify proteins that vascular cells express in order to deliver drugs more specific to organs. For instance, you may be able to deliver a drug specifically to treat heart disease without affecting the liver or brain. This way you avoid toxic side effects. In tumors, you would like the anti-tumor agent targeting the tumor without negatively affecting surrounding organs and tissues. Obviously, a better understanding of what is different in blood vessels at the tumor site is essential to tailor drugs more specifically to focus on the site of disease.
NHW: How can you use the therapy to stop tumor growth in cancer?
MC: A tumor produces an angiogenic vessel growth factor, called vascular endothelial growth factor (VEGF), which supports the action of TNF (tumor necrosis factor) only to the blood vessels within the tumor. By studying signal transduction, we were able to identify the so-called intracellular switch inside the cell that enhances the action of TNF throughout the vascular endothelium. The knowledge that tumor vasculature is different from normal vasculature led to the employment of new medications which can localize the effect of TNF more specifically to the tumor vasculature. The new tailored medications resulted in thrombotic occlusions in the tumor and subsequent regression. When blood flow to the tumor is stopped, the tumor dies.
NHW: How do you identify the target of a particular drug and tailor the medication to attack that particular disease, organ or tissue?
MC: We are identifying the targets, drawing on findings from the field of proteomics and identifying the overall protein composition in cells or disease states. We are focusing on the proteins expressed on the blood side of our blood vessels. We can use these proteins as docking sites for other compounds that can specifically bind to these proteins.
NHW: Are you also identifying better methods to promote new blood vessel growth in, for example, heart disease?
MC: We are identifying signaling molecules that can stimulate blood vessel growth, or angiogenesis, but at the same time prevent vessels from becoming leaky. One side effect of VEGF is leaky vessels, a condition that can cause edema, or the accumulation of water in the tissue. We identified molecules that can distinguish blood vessel growth and vascular leakage, so we can specifically develop drugs to better support blood vessel growth with fewer side effects.
NHW: Are you working with the Indiana Genomics Initiative (INGEN) at Indiana University?
MC: Yes. INGEN is one of the reasons that I came to Indiana from Germany. With INGEN, Indianapolis is competitive worldwide in this field of translation of the human genome into biomedical function. This rapid development in turn gives chances to patients to get a remedy or treatment that wasn’t even thought about 10 years ago.
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