For further information go to; www.daltonlab.uga.edu Our work focuses on the generation of therapeutically useful cell types that can be used to treat cardiovascular disease, diabetes, stroke, autoimmune disease, spinal cord injury and neurological diseases. We are also interested in early development and how pluripotent cells contribute to the developing embryo.
We study how protein glycosylation affects cellular communication as well as protein folding using biochemical, cell biological and animal studies. The forms of glycosylation we study affect development, birth defects, and cancer.
Our research focuses on the function of glycoconjugates in the regulation of cell adhesion. 1) investigation of the mechanism how glycosyltransferases and oligosaccharide expression regulate cell adhesion, migration, and invasiveness; 2) structure and function of the glycosyltransferase GlcNAc-T V to develop an inhibitor as a cancer therapeutic; 3) identification of glycoprotein glycoforms diagnostic for carcinomas; 4) function of a novel endothelial cell lectin, most likely in pathogen surveillance; 5) structural determination of a new family of animal and fungal lectins, the X-type lectins; 6) functions of lectins in animal development and as ligands for BT toxins.
Our laboratory utilizes multiple model systems including zebrafish to study the developmental consequences of impaired lysosomal catabolism of glycoproteins. We are focused on understanding how the mislocalization and inappropriate activity of specific enzymes impacts the normal development and function of several tissues including cartilage.
Specific cell surface oligosaccharides function as identity tags, allowing cells to appropriately interact with each other and with their environment. We utilize genetic, molecular, and chemical techniques in vertebrate (mouse) and insect (Drosophila) model systems to study two aspects of carbohydrate expression: 1) the influence of cell surface carbohydrates on development of the nervous system, 2) mechanisms that control tissue- and stage-specific oligosaccharide expression. Our results have implications for facilitating regeneration of axon pathways in the nervous system, for understanding innate immunity and tissue surveillance, and for controlling the cellular changes that precede tumor metastasis.
Research in the Wang laboratory focuses on the structure and function of heparan sulfate proteoglycans in vasculature and cancer biology. Heparan sulfate proteoglycans are glycoconjugates which are abundant on the cell surface and in the extracellular matrix. In vitro studies have suggested that heparan sulfate proteoglycans interact with growth factors, growth factor binding proteins, extracellular proteases, protease inhibitors, chemokines, morphogens, and cell adhesive proteins to modulate cell differentiation, proliferation, migration, blood coagulation, lipid metabolism, and leukocyte trafficking. However, the biological and pathological functions of heparan sulfate proteoglycans in vivo are still largely unknown. Using techniques, including conditional mouse gene targeting, embryonic stem (ES) cell differentiation, primary cell culture, and mouse models, the Wang lab is aiming to understand the roles and the underlying mechanisms of heparan sulfate proteoglycan in vascular development, cancer biology and blood coagulation in vivo, and to develop novel approaches to cure the related pathological conditions.
Our laboratory is interested in how post-translational modifications of proteins increase functional diversity. Primarily, we are interested in glycosylation, with a focus regarding: 1. O-GlcNAc in Type II diabetes and stem cell biology 2. O-Mannosylation in Congenital Muscular Dystrophy and viral entry into host cells 3. Glycoproteins as biomarkers in human disease, specifically pancreatic cancer and metabolic syndrome 4. Development of technology-based approaches, primarily mass-spectrometry, for quantitive proteomics/ glycomics/ glycoproteomics.
Glycosylation regulates the activities of proteins via multiple intrinsic and extrinsic mechanisms. A remarkable example, in our laboratory’s view, is the glycosylation of a subunit of the E3(SCF)ubiquitin ligases, Skp1. Skp1 glycosylation, which depends on its prior oxygen-dependent prolyl hydroxylation, promotes assembly and presumably the activities of this enzyme family toward the degradation of a whole host of cell regulatory factors. This mechanism underlies oxygen-sensing by a variety of unicellular organisms, including the social amoeba Dictyostelium and the human pathogen Toxoplasma gondii. Our multidisciplinary approaches to understand this mechanism, and exploit our understanding to control parasite virulence, embrace structural biology, metabolomics, bioinformatics, molecular genetics, enzymology, cell and developmental biology, and parasitology.