We are studying the pathogenesis of the fatal myoclonous epilepsy, Lafora Disease. Lafora Disease is a disease where abnormal polyglucosan accumulations form in Lafora Bodies in dendrites and perikaryon in the brain, sweat glands, muscle and liver. At present two gene products have been identified (malin and laforin) and the focus has been to identify their role in glycogenesis and how their absence results in the formation of these abnormal polyglucosans.
The intercalated disk in cardiac myocytes of patients affected with arrythmogenic right ventricular cardiomyopathy (ARVC), a cause of sudden death in the young is being studied using electron tomography. In addition, proteins associated with the intercalated disks that have been implicated as playing a role in ARVC are also being investigated.
A microfluidic device capable capable of retaining liquid at one atmosphere with an electron lucent partition membrane has been developed for the observation of cells in a hydrated state in the scanning electron microscope. Cells can be grown on the internal face of the electron lucent partition membrane and viewed either live or processed using a number of protocols including conventional electron microscopy fixation and staining procedures including cytochemistry and immunogold immunocytochemistry. The capsule is sealed and the cells imaged using backscatter electron (BE) imaging. Images, although limited to portions of the cells in intimate contact with the partition membrane, far exceed the resolution of the confocal microscope and other light optical methods .We are currently able to obtain serial images of the same cell over 8 hour periods.