Nhat Le

Throughout my scientific career, I have received broad academic training in biochemistry, genetics, cell biology and neurobiology. With a long-standing interest in protein misfolding and neurodegeneration diseases, I am particularly interested in studying the molecular and cellular mechanism underlying neurotoxicity. My Ph.D. degree in the field of the neurodegenerative disease provided me with training in prion diseases and prion-like disorders, skills in protein biochemistry and cell biology, and mouse behavior. My first postdoctoral position gave me the opportunity to extend my research into amyotrophic lateral sclerosis (ALS), and to learn about mouse transgenic models and disease mechanisms. Drawing on this knowledge and my previous work with prion-proteins, I am currently researching the mechanism of prion neurotoxicity, particularly the cellular signaling pathways responsible for degeneration of synapses. I am using mouse models of these diseases, cultured primary neurons, and iPSC-derived neurons from prion patients to study the very earliest effects of prion infection, as well as testing therapeutic compounds.

Within Dr. Harris’s laboratory, I benefit from the multi-disciplinary approach being used. I am collaborating with several experts at Boston University, who are expanding my expertise in omics and stem cells, which will contribute significantly to the success of my research. My studies make use of cutting-edge proteomics (mass spectrometry), transcriptional profiling (RNA-seq), and sophisticated bioinformatics pipelines. These experiments are the first to undertake global analysis of changes in gene expression and protein phosphorylation in neurons undergoing well-defined changes in synaptic structure and function in response to prions. The results will greatly expand the list of potential therapeutic targets capable of blocking synaptotoxic processes in prion diseases. The project could also lead to development of novel CSF biomarkers. By applying iPSC technology, I have established a powerful new experimental platform, based on differentiated neurons derived from human patients carrying prion disease-causing mutations, which can be used to study the mechanisms by which prions damage neurons, and to test the efficacy of novel therapeutic compounds. This current work represents a highly synergistic combination of my previous experience in neuronal cell biology with my stem cell expertise.