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Leslie Thompson

UCI MIND’s Leslie Thompson has worked on Huntington’s disease for over two decades, and her group’s research has revealed extensive insights into the biological underpinnings of the disease. During the week of July 15, her laboratory adds to its impressive log of discoveries.

Thompson is the lead author for studies appearing in the Proceedings of the National Academy of Sciences and Cell Reports that identify new and well-defined molecular targets for drugs that can treat the fatal neurodegenerative disease.

In the journal Cell Reports, published on July 18, Thompson and colleagues identify how two proteins – SUMO-2 and PIAS1 – help control the accumulation of the Huntingtin protein in brain tissue.  This accumulation is central to disease progression. And in the PNAS article, also published this week, Thompson and colleagues explore the genetics of HD, reporting that targeting a histone-modifying enzyme (H3K4 demethylase) can normalize the expression of certain aberrant genes that promote disease progression.

“The molecular activities we identified represent defined therapeutic targets,” says Thompson, a professor of psychiatry & human behavior and neurobiology & behavior. “However, they also both reveal fundamental mechanism of diseases related to the human brain, and underscore the importance of basic science research on neurodegenerative diseases.”

Thompson added that each study was the result of years of research by lab investigators Jacqueline Gire O’Rourke (first author, Cell Reports study) and Malini Vashishtha (first author, PNAS study).

Key UC Irvine study contributors also include Joseph Ochaba, J. Lawrence Marsh and Joan Steffan (Cell Reports); and Alice Lau and Marsh in collaboration with the laboratories of David Housman and Ernest Fraenkel at the Massachusetts Institute of Technology (PNAS).