| Matt Schenauer
Department of Chemistry
Genome Center
University of California
Davis, CA 95616
(530) 754-4038
sestosterschen@gmail.com | Position: | Graduate Student | | Education: | B.S. in Biochemistry, University of Nevada, Las Vegas, 2003 | | Research Topic: | | | Research Summary: | Chemokines are class of cytokines known to influence the migration of leukocytes from the bloodstream and lymph in processes such as inflammation, angiogenesis, wound healing and metastases. Chemokines exert this function by binding to 7-pass transmembrane G-protein coupled receptors in the leukocyte cellular membrane. More than 45 human chemokines and 18 receptors have been identified to date. Significant cross-reactivity has been observed in vitro with multiple chemokines signaling through a single receptor and likewise single receptors bind to multiple chemokines. Based on these studies, the chemokine/receptor interaction has thus been deemed redundant. However, this so-called redundancy is not observed in vivo where knockout mutations, individual chemokine-targeted antibodies, and specific small molecule inhibitors exhibit significant defects in the inflammatory process in mouse models.
If not at the receptor, then where is the specific in vivo chemokine response derived?
Chemokines also bind to a class of molecules known as glycosaminoglycans (GAGs). GAGs are linear, highly sulfated, acetylated polysaccharides that are components of the extracellular matrix and complexed with core proteins of cellular membranes as proteoglycans. GAGs are divided into sub-families, each with characteristic features, while the sequence of individual polysaccharide chains can vary within each class. Minimally GAGs are thought to facilitate the formation of highly concentrated chemokine gradients at their site of production, but an emerging hypothesis and preliminary evidence suggests that GAGs may offer specificity to the in vivo chemokine/receptor interaction. My research project aims to characterize the important noncovalent interactions between chemokines and glycosaminoglycans via high resolution FT-ICR (Fourier transform- ion cyclotron resonance) and tandem mass spectrometry.^M^M | | |
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