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CSB Seminar Series – Denise Montell, PhD – UC Santa Barbara
October 25 @ 11:00 am - 12:00 pm
CSB Departmental Seminar
Denise Montell, PhD
UC Santa Barbara
TITLE: Harnessing fundamental cell biology in Drosophila for improved treatments of cancer and neurodegenerative disease
ABSTRACT:
In the course of investigating molecular and genetic mechanisms of collective border cell migration in the Drosophila ovary, we uncovered that expressing constitutively active Rac is sufficient to cause cells to engulf and kill living target cells. We found that this mechanism likely underlies a rare human genetic immunodeficiency and we are harnessing this technology to improve CAR-M cancer immunotherapy. A second border cell migration mutant led us to discover that cytosolic Zn2+ is rate limiting for proteasome activity, specifically for the Rpn11 Zn2+ metalloprotease in the proteasome lid. Overexpression of the ER Zn2+ transporter ZIP7 prevents retinal degeneration caused by mutations that cause rhodopsin to misfold in the ER in a fly model of retinitis pigmentosa. ZIP7 is deeply conserved in evolution and its loss causes ER stress in cells from organisms as diverse as plants and humans. However the beneficial effects of ZIP7 overexpression were previously unknown as was its mechanism of action. Overexpression of human ZIP7 also stimulates deubiquitination of misfolded proteins. We are investigating ZIP7 overexpression as a potential gene therapy for retinitis pigmentosa and other neurodegenerative diseases cause be toxic misfolded proteins.
HOST: Student Invitee – Ernest Iu, Plotnikov Lab
LOCATION: Cell and Systems Biology, 25 Harbord Street, Suite 432
VIRTUAL SEMINAR: https://csb.utoronto.ca/live-stream/