A CRISPR approach to neurodegenerative diseases

When Martin Kampmann, Ph.D., set out to explore the workings of the human brain, he was captivated by its greatest mystery: how a network of cells could produce something as intangible as thoughts, emotions, memories, and even consciousness.

His desire to view biology beyond a molecular lens ultimately led him to UCSF for postdoctoral training in the lab of Jonathan Weissman, PhD, who at the time was a professor in the Department of Cellular and Molecular Pharmacology. As a postdoc, Kampmann led the creation of a tool that helps scientists find important human genes involved in specific cell processes and understand how those genes work together in complex networks.

"The timing was great because CRISPR technology was just being developed by [UC Berkeley biochemist and Nobel laureate] Jennifer Doudna," Kampmann said. "We were able to take advantage of these exciting new technologies to build a CRISPR-based genetic-screening platform, which allowed us to systematically study genes across the human genome. The purpose was to identify which genes play important roles in specific cellular processes and better understand their functions."

Kampmann credits UCSF's collaborative environment and bold research culture with helping him make the leap from biochemistry to neuroscience. One especially fruitful collaboration has been with the Memory and Aging Center's Neurodegenerative Disease Brain Bank, led by Lea Grinberg, MD, PhD, the John Douglas French Alzheimer's Foundation Professor, and William Seeley, MD, the Zander Family Distinguished Professor of Neurology.

Together, they used advanced genetic research methods to identify, for the first time, the specific molecules found in the neurons most affected by Alzheimer's disease in the brain region that shows early signs of the condition.

"UCSF is one of the few places in the world where innovative strategies are able to succeed because of the robust neuroscience community support," Kampmann said. "These kinds of partnerships ground our discoveries and make our models stronger."

The power of people and data

Kampmann's research is now focused on how human cells maintain healthy and balanced proteins, a process known as "proteostasis." By studying the network of systems inside cells that protect and manage proteins, Kampmann aims to understand how this network breaks down or changes in diseases like cancer and Alzheimer's.

One finding he found particularly surprising was the identification of a previously unknown protein that signals when mitochondria - the parts of cells that produce energy - are under stress. This discovery has shaped research into how cells respond to damage and what goes wrong in diseases like Alzheimer's. Kampmann's also leveraging artificial intelligence (AI) to uncover the drivers of changes in neural activity during the early stages of neurodegeneration.

"There's untapped potential in finding better ways to computationally integrate data that people have generated in human genetics and uncover patterns that we can then test in the lab," Kampmann said. "We're already using AI to understand what controls changes in neural activity that are seen early on in neurodegenerative diseases."

Looking ahead, Kampmann is optimistic, but realistic, about reaching his ambitious goal: unlocking the mechanisms of neurodegenerative diseases to develop new treatments.

"I'm extremely grateful for the Byers Award because it is unrestricted funding that enables us to do high-risk, high-reward research," Kampmann said. "We can try big, bold, new ideas that we believe could lead to a major breakthrough."

For Brook Byers, the impact of his investment in UCSF has gone far beyond advancing science. It has created lasting personal connections and a sense of shared purpose, as seen in the anniversary video that was featured during the lecture.

"Our family has enjoyed our philanthropic relationship with UCSF over many years. It has opened the opportunity to get to know scientists and clinicians on a personal level," Byers said. "Now more than ever, basic science needs our support to drive discoveries that can improve lives."

2025 Byers Award