Jacob Klickstein

Protein quality control is an essential part of cellular homeostasis and maintenance of proper cellular function for every cell in the body. The ubiquitin - proteasome pathway is an important mediator in clearance of misfolded, aggregation-prone proteins from the endoplasmic reticulum, cytoplasm and other intra-cellular compartments. The Raman lab is investigating the role of the AAA+ ATPase VCP/p97 and it's adapters in the ubiquitin - proteasome pathway. My project will focus on the role of this protein in protein aggregation disorders such as ALS and multisystem proteinopathy which includes inclusion body myopathy, Paget's disease of the bone and frontotemporal dementia. Certain mutations in VCP/p97 have been shown to cause familial forms of these diseases; however, the link between protein malfunction, aggregation and clinical symptoms has yet to be uncovered. I hope to elucidate the salient processes behind VCP/p97 function and dysfunction and the development of these diseases using an neuronal iPSC model of ALS and discovering changes in protein expression using tandem mass tag proteomics.