Caltech Professor Receives “High-Risk, High-Reward” Research Award

Henry Lester, Bren Professor of Biology and Biological Engineering, has received a Transformative Research Award from the National Institutes of Health (NIH) as part of the NIH’s High-Risk, High-Reward Research (HRHR) program. The Transformative Research Award, established in 2009 and awarded this year to 12 scientists, supports “exceptionally innovative, unconventional, paradigm-shifting research projects that are inherently risky and untested,” according to the NIH press release.

Since he arrived in 1973, Lester has spent his entire professorial career at Caltech. His research now focuses on the actions of drugs on the ion channels, receptors, and transporters of “excitable cells”—cells such as neurons and muscle fibers that use electrical signals. Lester helped to pioneer “inside-out” neuropharmacology, which studies how the interaction of nicotine and nicotine receptors in an organelle called the endoplasmic reticulum leads to the addictive effects of nicotine, and in some cases to neuroprotective effects.

With this award, Lester will study the mechanisms by which certain psychiatric drugs exert their therapeutic effects, as well as how additional addictive drugs such as opioids work. He hypothesizes that these drugs also work “inside-out,” binding first to molecular targets within organelles in cells. He and his group aim to develop genetically encoded fluorescent biosensors to measure drugs within organelles.

“Nicotine has served as a model for neuroscience and pharmacology ever since Columbus’s crew sampled tobacco,” says Lester. “Caltech continues to support our work on the hypothesis that insights from nicotine help to explain psychiatric and addictive drugs, and this grant provides both additional validation and much-needed support.”

Lester has more than 330 publications and nine US patents. He has served as chair of the Caltech faculty and as president of the Biophysical Society. He participates on the California Council for Science and Technology.

This year, the HRHR Program, supported by the NIH’s Common Fund, awarded 88 grants in four categories: 12 Pioneer awards, 48 New Innovator awards, 12 Transformative Research awards, and 16 Early Independence awards.