Christa Hestekin

HestekinInvestigation of early stage protein aggregation using microchannel electrophoresis

Early stage protein aggregation has been implicated in a variety of diseases in includeing alzheimer's disease and diabetes. Alzheimer's Disease (AD) is a complex and devastating neurodegenerative disease.  Currently, AD is believed to progress from harmless amyloid beta (Aβ) monomers through a nucleation step to oligomeric species and then larger aggregates.  There is a need to develop a technique that can detect the aggregation of early species (oligomers) at physiological concentrations with rapid analysis times.  Microchannel electrophoresis offers an attractive approach for detecting low concentration, transient species that may be key to the development of Alzheimer’s disease.  The Hestekin lab has previously explored the use of microchannel electrophoresis to investigate the effects of solution conditions and sample preparation on the oligomeric, pre-beta sheet aggregates.  The lab is currently focused on investigating changes to the primary sequence that alter the protein’s aggregation in an effort to understand the driving mechanism.  The information gleaned from these studies could be used to enhance drug design.  In addition, the conditions for physiological detection of protein aggregates using fluorescent labels as well as the separation and identification of individual oligomeric species are also being explored.