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Theoharis C. Theoharides, M.D., Ph.D. |
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Professor of Pharmacology and Experimental Therapeutics
Biochemistry, Pharmacology
theoharis.theoharides@tufts.edu
Our laboratory investigates the secretory mechanism of cytokines and other proinflammatory molecules from a unique bone-marrow drived cell, the mast cell, commonly known for its involvement in allergic reactions. We have shown for the first time that mast cells can be activated by corticotropin-releasing hormone (CRH), the first molecule generated under stress, and interleukin-1 to release cytokines selectively through a unique process involving microvesicles. We have further shown that CRH-activated mast cells lead to vascular permeability investigated by extravasation of 99-Technetium gluceptate. This process can initiate sterile inflammation and may participate in the pathophysiology of conditions that worsen or precipitate under stress such as multiple sclerosis, migraines, psychogenic asthma, inflammatory arthrits, unstable angina, eczema, and interstitial cystits. We are currently investigating the expression of CRH receptors on mast cells in vitro and in situ, as well as ithe pathophysiological implications of their activation in animal models. We are also investigating the sitmulus-response coupling of CRH activated mast cells, and have cloned a protein that inhibits this process upon phosphorylation of unique sites in response to specificf lavonoids. This work has led to a number of patents and clinical trials.
Visit the Theoharides research web site |
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