MINDS - Dr. Phedias Diamandis - Spatiotemporal Proteomic Profiling of Human Neurodevelopment & Neuropathologies

Description

Where: HSC/4E20


Spatiotemporal Proteomic Profiling of Human Neurodevelopment & Neuropathologies

Bio: I completed my Doctoral, Medical and Residency training in Neuropathology here at the University of Toronto. I carried out my PhD work under the mentorship of Professors Peter Dirks and Mike Tyers in neural stem cell and cancer stem cell biology. By harnessing the chemical diversity housed within small molecule libraries, we were able to uncover novel regulators of neural and cancer stem cell function. 


Our current research program focuses on strategic application of contemporary and comprehensive molecular tools to improve our understanding of neurobiology, neuroanatomy and microscopic characterization of disease. Our most recent large scale efforts have focused on mass spectrometry based proteomic methods to profile human neural tissue and expand our understanding of cancer and neurodevelopment. We use the generated datasets as a springboard for more focused mechanistic studies and novel biomarker discovery of neuropathological diseases. We also work on the application of computer vision and deep learning to augment clinical decision making. 



Abstract: Mass spectrometry (MS) analysis of human post-mortem central nervous system (CNS) tissue and induced pluripotent stem cell (iPSC)-based directed differentiations offer complementary avenues to define protein signatures of neurodevelopment. Methodological improvements of formalin-fixed, paraffin-embedded (FFPE) protein isolation now enable widespread proteomic analysis of well-annotated archival tissue samples in the context of development and disease. Here, we utilize a shotgun label-free quantification (LFQ) MS method to profile magnetically enriched human cortical neurons and neural progenitor cells (NPCs) derived from iPSCs. We use these signatures to help define spatiotemporal protein dynamics of developing human FFPE cerebral regions. We show that the use of high resolution Q Exactive mass spectrometers now allow simultaneous quantification of >2700 proteins in a single LFQ experiment and provide sufficient coverage to define novel biomarkers and signatures of NPC maintenance and differentiation. Importantly, we show that this abbreviated strategy allows efficient recovery of novel cytoplasmic, membrane-specific and synaptic proteins that are shared between both in vivo and in vitro neuronal differentiation. This study highlights the discovery potential of non-comprehensive high-throughput proteomic profiling of unfractionated clinically well-annotated FFPE human tissue from a diverse array of development and diseased states.

Location information

1200 Main St W, Hamilton, ON L8N 1H4, Canada

Country
Canada
County
Ontario
City
Hamilton L8N 1H4
Street
1200 Main Street West

Contact Department

Department of Psychology, Neuroscience & Behaviour (PNB)
Psychology Building (PC), Room 102
McMaster University
1280 Main Street West
Hamilton Ontario L8S 4K1
Canada