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 the mechanism and consequences of Ty1 retrotransposition in the budding yeast Saccharomyces. Ty1 elements are similar to retroviruses such as HIV and other retroelements that comprise almost half the human genome. We would like to understand how Ty1 and budding yeast coexist using a combination of genetic, molecular, and structural approaches. In particular, we have discovered a novel self-encoded derivative of the Ty1 capsid protein that modulates retrotransposition in a dose-dependent manner by restricting virus-like particle assembly and function.
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.
Research in my lab is at the intersection of genome biology, evolutionary biology and computational structural biology. We combine techniques and approaches from these diverse disciplines to understand the underlying mechanisms of signaling proteins in atomic detail.
Pectin is a family of complex polysaccharides present in all plant primary cell walls. Pectin plays multiple roles in plant growth, development, and defense responses; in part through contributing to cell wall strength, wall ion exchange and sieving properties, cell-cell adhesion, and cell-cell communication. Pectin is a food fiber and a commercial gelling agent that has beneficial effects on human health. Our long term goal is to decipher how the 53 distinct enzyme activities required for pectin synthesis interact to synthesize pectin and to modify pectin synthesis in order to study pectin function. Towards this goal we are purifying, cloning, and characterizing the biosynthetic enzymes; many of which are Golgi localized and membrane bound enzymes. Current emphasis is on the galacturonosyltransferase and the methyltransferase that synthesize the pectic polysaccharide homogalacturonan.
Research in the Moremen lab focuses on the structure, enzymology, regulation, and localization of enzymes involved in the biosynthesis, recognition, and catabolism of mammalian glycoproteins. Carbohydrate structures on glycoproteins contribute to many biological recognition events between molecules and between cells in an organism. Alterations in the synthesis and degradation of these structures can also occur in human genetic disease. Work in the Moremen lab is focused on (1) the characterization of enzymes involved in mammalian glycoprotein biosynthesis and catabolism and the functionally defective forms of these enzymes involved in human genetic disease and (2) the identification and characterization of carbohydrate-binding proteins and their roles in vertebrate development and physiology.
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.
Research in our lab is mainly focused on proteases:
The CaaX proteases: Rce1 and Ste24 mediate a proteolytic cleavage event associated with the maturation of proteins that contain a covalently attached isoprenyl lipid at their C-terminus (e.g. Ras, nuclear lamins, fungal pheromones). We are investigating the mechanism and specificity of these proteases in an effort to better understand their role in human disease (e.g. Ras and cancer; lamins and progeria).
The M16A proteases: This evolutionarily conserved metalloprotease family includes the human insulin-degrading enzyme, which mediates degradation of amyloidogenic peptides such as the Abeta peptide associated with Alzheimer’s disease. We are investigating the mechanism and specificity of these enzymes to better understand their physiological role in the cell.
Our research program is multi-disciplinary, allowing for exposure to the disciplines of biochemistry, cell biology, chemistry, genetics, and microbiology.
Our research focuses on protein structure and function and protein-protein interactions. We employ an approach combining modern analytical, biophysical and molecular biology techniques, with an emphasis on biomolecular NMR spectroscopy. Our core projects include the study of gene regulation and novel regulators of transcription initiation in bacteria, oxidative stress and calcium signaling, steroid hormone (estrogen) receptor activation, and regulation of biofilm formation and pathogenesis in Pseudomonas aeruginosa. These projects are important fundamentally, and they important biomedically with respect to antibiotic target development, oxidative stress and biological aging, and diseases such as breast cancer and cystic fibrosis.
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.