Andrew Miranker, PhD

Research in our laboratory is focused on conformational changes in proteins which give rise to a special class of protein complex known as amyloid fibrils. This folding problem is particularly fascinating as proteins which are seemingly unrelated in primary sequence and in their native 3 dimensional structure form aggregates which share common structural features. Depending on the protein involved, fibril formation gives rise or contributes to the pathogenesis of more than 20 clinical conditions. Projects currently underway in the laboratory include the islet amyloid polypeptide system which forms fibrils in the pancreas of type II diabetics, and beta-2 microglobulin which forms deposits on the connective tissues of long term dialysis patients. We are studying both the folding and the fibrillogenesis properties of these systems. Biophysical techniques enable these investigations to be conducted at a molecular level. These include high field NMR, optical spectroscopy and electrospray ionization mass spectrometry.