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Susan Lindquist, Ph.D.

NanoString Abstract Contest Winner  |  Whitehead Institute for Biomedical Research

Modulating the Heat Shock Response to Treat Cancer and Neurodegenerative Disease

Cellular heat-shock response (HSR) is a highly evolved and broadly protective mechanism that helps living organisms cope with a variety of physical stressors. While beneficial to survival for healthy cells or aging neurons, the normal heat-shock response is co-opted by cancer cells to enhance their ability to survive in the crowded, tangled and rogue state characteristic of malignancy.

At the Whitehead Institute, Dr. Susan Lindquist and her team have discovered new information about how the HSR operates in cancer as well as in modulating aging and the development of age-related neurodegenerative diseases. The team is applying their discoveries to the pursuit of new treatments designed to either up- or down-regulate HSR protein production.

According to Dr. Lindquist, the stress response involves several hundred changes in gene expression in every cell type, so they need to look at all of these genes. “NanoString provides a wonderful new method that hits the sweet spot where you can study the expression of a few hundred genes with a high degree of precision – and it’s less expensive than the other methods that are out there for quantifying changes in gene expression."

Dr. Lindquist’s winning proposal is designed to conduct further studies of the HSR with an nCounter probe set encompassing genes involved in elements of the oxidative stress defense response, and the regulation of chaperone proteins, metabolism and growth factors. She also plans to test how cells respond to a host of potential small molecules that may modulate the HSR, including natural products derived from desert plants.

“The NanoString nCounter system will significantly accelerate our rate of discovery by providing a flexible platform for executing stringent, biologically sophisticated and cost-effective secondary assays,” said Dr. Lindquist. “These assays will allow us to de-convolute primary screen hits and to more efficiently prioritize and select compounds for pre-clinical development, which we expect to initiate within the next year."