Research in the Lazo lab is focused on the biophysics of misfolding and self-assembly of proteins associated with disease. Proteins of interest include the amyloid ß-protein in Alzheimer’s disease, islet amyloid polypeptide associated with type 2 diabetes, the prion protein in various forms of prionoses, and skin proteins linked to epidermolysis bullosa, a disease characterized by skin blistering following little or no trauma. A combination of biophysical and biochemical methods including NMR spectroscopy, limited proteolysis/mass spectrometry, circular dichroism, and electron microscopy is used to investigate key events in protein misfolding and self-assembly. Knowing these events at the atomic level may lead to the development of therapeutics. Other research interests include NMR spectroscopy of membrane proteins, methods development, and the structure and dynamics of amyloid fibrils and intermediate filaments.
Current topics include….
- Elucidation of the early events in protein self-assembly at the atomic level
- Discovering small molecules that completely inhibit the self-assembly of highly amyloidogenic peptides and proteins
- Elucidation of the mechanisms for amyloid detection and inhibition by small molecules