Broadly, I am interested in the contribution of adaptive stress signaling to neurodegenerative diseases and aging and in the prospect of utilizing these pathways as therapeutic targets.
Protein homeostasis is maintained through an intricate network of organelle specific stress responses. Loss of proteostasis is a hallmark of most age-associated diseases including neurodegenerative diseases and the aging process itself. Proteotoxic stress signaling, including the heat shock response (HSR) and different organelle specific unfolded protein responses (ER UPR and mtUPR) has been traditionally studied in a cell autonomous manner using a limited number of cell models. Yet it is increasingly recognized that the nature of these responses highly depend on the cell type and on extrinsic effectors as metabolism and signaling between cells.
During the first two years of my postdoc at the Zhang lab we pioneered the use of pooled CRISPR libraries for functional knockout screening in mammalian cells. CRISPR based screens displayed remarkable results with high perturbation efficacy, high target specificity, and most importantly, in the few initial screens, revealed an order of magnitude more validated gene hits than previous RNAi based screens.
In my current work I combine technology development of large scale perturbation screens with the application of such technology to the study of proteotoxic stress responses and their malfunction in neurodegenerative diseases. I am developing models to study this in human cell lines, stem cell derived cells and mouse primary cells with the aim of understanding the effect of genetic variation and aging on these networks.
For a more detailed research plan please contact me directly.