Biomedical subjects

Patricia LiWang

Publications and source records attributed to Patricia LiWang.

3 recordsLinked to original sources

PubMed2006

Detecting protein dissimilarities in multiple alignments using Bayesian variable selection.

MOTIVATION: We present an application of Bayesian variable selection to the novel detection of sequence elements that confer negative design to protein structure and function. As an illustration, we analyze the different dimer interfaces between the CXCL8 chemokine family with the CCL4 and CCL2 chemokine families to discover the changes that disfavor CXCL8 of quaternary structure. RESULTS: In comparison with known experimental results, our method identifies evolutionarily conserved sequence changes in the CC families that inhibit CXCL8 quaternary structure. Therefore, we find positive selection of negative design elements. Furthermore, our approach predicts that a two-residue deletion conserved in the CCL4 chemokine family disfavors CXCL8 dimerization. AVAILABILITY: The Matlab code for the Bayesian variable selection is freely available at http://stat.tamu.edu/~mvannucci/webpages/codes.html

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PubMed2003

Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines.

During organogenesis, immunosurveillance, and inflammation, chemokines selectively recruit leukocytes by activating seven-transmembrane-spanning receptors. It has been suggested that an important component of this process is the formation of a haptotactic gradient by immobilization of chemokines on cell surface glycosaminoglycans (GAGs). However, this hypothesis has not been experimentally demonstrated in vivo. In the present study we investigated the effect of mutations in the GAG binding sites of three chemokines, monocyte chemoattractant protein-1/CC chemokine ligand (CCL)2, macrophage-inflammatory protein-1beta/CCL4, and RANTES/CCL5, on their ability to recruit cells in vivo. These mutant chemokines retain chemotactic activity in vitro, but they are unable to recruit cells when administered intraperitoneally. Additionally, monomeric variants, although fully active in vitro, are devoid of activity in vivo. These data demonstrate that both GAG binding and the ability to form higher-order oligomers are essential for the activity of particular chemokines in vivo, although they are not required for receptor activation in vitro. Thus, quaternary structure of chemokines and their interaction with GAGs may significantly contribute to the localization of leukocytes beyond migration patterns defined by chemokine receptor interactions.

Animals↗

PubMed2003

Optimization of gene expression in nonactivated circulating lymphocytes.

Circulating lymphocytes are important target cells for the treatment of HIV-related and autoimmune diseases and for stimulating anti-tumor immunity. To date, gene transfection of these nonactivated cells after intravenous delivery of viral or nonviral vectors remains low although these circulating cells are highly accessible. Optimized lentiviral vectors currently can transduce less than 10% of nonactivated circulating lymphocytes. Here we report transfection of up to 15% of these nonactivated cells using liposomes directed to human CCR5 displayed on the surface of helper T cells and macrophages in transgenic mice. Attachment of modified MIP-1 beta to the surface of DNA-liposome complexes increased gene delivery and expression in nonactivated circulating lymphocytes approximately sixfold. In vitro data using these complexes to transfect PM1 cells that have elevated levels of CCR5 supported our data obtained in vivo. Therefore, ligands that bind to cell surface receptors on circulating lymphocytes can be used with optimized systemic liposomes to increase transfection and gene expression in these cells without activation.

Animals↗