The primary objective of the Resource for Integrated Glycotechnology is the development of multidisciplinary approaches to the solution of problems in glycobiology. A particular focus is a subset of problems related to glycosaminoglycan function. Glycosaminoglycans such as heparin, heparan sulfate, and chondroitin sulfate play important roles in modulating intracellular signaling, influencing the migration of immune cells to sites of infection, controlling angiogenesis in tumors, and regulating regeneration of neurons. They also serve as receptors for pathogenic organisms. To fulfill these roles, binding proteins interact with specific regions of these glycosaminoglycans. Understanding these interactions is an important step toward intervention in human disease, yet little information is available on the specific sequences recognized, the structural aspects of the interactions, or they way in which interactions result in cellular response. The lack of information is in part due to the extraordinary complexity of the sequences of these carbohydrate based polymers. The Resource develops technology to provide this information by combining advances in separation and synthesis of glycosaminoglycan oligomers that display binding specificity, in mass spectrometry (MS) based means of identifying oligomer structures, in nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry based means of defining three dimensional structures of complexes, in computational modeling and prediction of glycosaminoglycan-protein interactions, and in cell and biochemically based means of monitoring a biological response. The technology development is driven by selected driving biomedical projects with external collaborators. These include ones that address the function of Robo-Slit signaling in angiogenesis, the function of DLB domains in survival of the malaria parasite in placental infection, the specificity of glycosaminoglycan binding antibodies in detection of cellular abnormalities, and the regulation of immune cell migration by chemokines. Technology is disseminated through extensive training programs and additional collaborations and service functions hosted by the Resource.
The interactions between glycosaminoglycans such as heparin, heparan sulfate, and chondroitin sulfate, and a variety of proteins involved in cellular signaling or cellular adhesion play important roles in human disease. These diseases include developmental abnormalities, cancer, coronary disease, a number of immune disorders and parasite invasion, malaria, for example. Understanding the molecular basis of specificity in these interactions is an essential component in the rational design of agents the can combat disease. The Resource for Integrated Glycotechnology develops methods that can provide this understanding.
|Lak, Parnian; Makeneni, Spandana; Woods, Robert J et al. (2015) Specificity of furanoside-protein recognition through antibody engineering and molecular modeling. Chemistry 21:1138-48|
|Lu, Jingning; Auduong, Linda; White, Eric S et al. (2014) Up-regulation of heparan sulfate 6-O-sulfation in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 50:106-14|
|Makeneni, Spandana; Ji, Ye; Watson, David C et al. (2014) Predicting the Origins of Anti-Blood Group Antibody Specificity: A Case Study of the ABO A- and B-Antigens. Front Immunol 5:397|
|Chuang, Yen-Jun; Zhen, Zipeng; Zhang, Fan et al. (2014) Photostimulable near-infrared persistent luminescent nanoprobes for ultrasensitive and longitudinal deep-tissue bio-imaging. Theranostics 4:1112-22|
|Prestegard, James H; Agard, David A; Moremen, Kelley W et al. (2014) Sparse labeling of proteins: structural characterization from long range constraints. J Magn Reson 241:32-40|
|Hadden, Jodi A; French, Alfred D; Woods, Robert J (2014) Effect of microfibril twisting on theoretical powder diffraction patterns of cellulose I? Cellulose (Lond) 21:879-884|
|Zhang, Bing; Xiao, Wenyuan; Qiu, Hong et al. (2014) Heparan sulfate deficiency disrupts developmental angiogenesis and causes congenital diaphragmatic hernia. J Clin Invest 124:209-21|
|Kailemia, Muchena J; Ruhaak, L Renee; Lebrilla, Carlito B et al. (2014) Oligosaccharide analysis by mass spectrometry: a review of recent developments. Anal Chem 86:196-212|
|Zhen, Zipeng; Tang, Wei; Chuang, Yen-Jun et al. (2014) Tumor vasculature targeted photodynamic therapy for enhanced delivery of nanoparticles. ACS Nano 8:6004-13|
|Zhang, Fuming; Moniz, Heather A; Walcott, Benjamin et al. (2014) Probing the impact of GFP tagging on Robo1-heparin interaction. Glycoconj J 31:299-307|
Showing the most recent 10 out of 44 publications