Mass Spectrometry-based Proteomics and Lipidomics of Niemann-Pick Type C Reveals Disease Markers and Novel Insights to Biomolecular Alterations

Speaker: Dr. Stephanie Cologna, University of Illinois-Chicago

Host: Dr. Peter Nemes, UMCP

Abstract: Mass spectrometry-based proteomics and lipidomics are powerful strategies to understand molecular mechanisms associated with human disease. Our laboratory studies Niemann-Pick Type C (NPC), a fatal, progressive neurodegenerative disorder that arises due to improper trafficking of cholesterol. As a result of the genetic defects in NPC, cholesterol storage is observed in late endosome/lysosome compartments. Subsequently, a series of downstream events occur including neuroinflammation, calcium imbalance, oxidative stress and progressive neuron loss with the disorder being ultimately fatal in the early adulthood years. In an effort to understand pathways associated with the downstream consequences of the genetic cause of NPC, we have employed mass spectrometry imaging, quantitative proteomics and lipidomics in multiple models of NPC. Studies using the null Npc1 mouse model in our laboratory demonstrated protein changes that occur late in the disease and can be monitored during disease progression. Furthermore, we were able to use mass spectrometry-imaging of lipids along with untargeted lipidomics and proteomics to demonstrate that phosphoinositide lipid homeostasis is altered in NPC. Finally, we have embarked on investigation of altered proteins in cerebrospinal fluid of NPC patients. These studies have provided insight into novel markers of the disease and insight into molecular alterations that may lend to mechanisms driving cell death. I will share several examples of our bench to bedside approach to reveal markers of NPC disease using mass spectrometry.

Biochemistry Seminar