Clifford Lingwood , PhD
Molecular Structure & Function
University of Toronto
Department of Laboratory Medicine & Pathobiology
Cross appointed to the Department of Biochemistry
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- Glycolipid receptor function
- Verotoxin cytopathology
- HIV infection
- Glycolipid rafts
My laboratory is concerned with the molecular basis and physiology of glycosphingolipid (GSL) receptor function. Globotriaosyl ceramide (Gb3) binding is the mechanism by which verotoxin targets renal endothelial cells to initiate hemolytic uremic syndrome. Our studies on this interaction have led to our definition of a role for Gb3 in HIV infection also. Our interests are focused on the role of the glycolipid receptor lipid heterogeneity in determining the sensitivity of cells to verotoxin-induced pathology/trafficking and HIV binding and membrane fusion. We have made soluble GSL analogues which in large part mimic the properties of GSLs and prove effective as novel strategies against microbial pathogenesis. Gb3 is upgregulated in certain human tumour cells and VT is a potential novel antineoplastic. The role of the drug resistance efflux pump MDR1 in GSL biosynthesis and the soluble GSL mimics we have generated allow us to manipulate cellular GSL metabolism to provide new approaches to several genetic diseases in which GSL metabolism is aberrant.
Future Research Interests
Our future studies will attempt to define the functional components within glycolipids and their ligands. We will use the glycolipid mimics we have made to inhibit these interactions and prevent the clinical pathology they mediate. The use of verotoxin as an antineoplastic/antiangiogenic agent and GSL mimics to prevent HIV infection offers new directions in translational research.
Please visit the publications section in the Lingwood Lab website
Glycolipid Mimics and Methods of Use Thereof (US 5,973,128)