Collectively, neuropsychiatric and neurodegenerative diseases are leading causes of illness, disability and premature death worldwide. And while they are categorized separately, they have much in common.
Similarly, Martin Kampmann , PhD, who studies neurodegenerative diseases, and Anna Victoria Molofsky , MD, PhD, who studies neuropsychiatric diseases, have different focuses, but their work overlaps, and they often collaborate. So, it's fitting that both Kampmann and Molofsky are 2025 recipients of the Bowes Biomedical Investigator award.
Being named a Bowes Biomedical Investigator is such an honor because it allows me to really take risks."
The award is made possible by the William K. Bowes Jr. Foundation and supports scientists who take novel approaches and have the potential to make significant contributions to biomedicine. Recipients receive $1.25 million over five years.
Molofsky, the Samuel Barondes Professor of Neurobiology and Psychiatry and an associate professor in the Department of Psychiatry and Behavioral Sciences, has always been drawn to things that people consider unimportant. When she set up her own UC San Francisco lab in 2015, Molofsky was contemplating areas that she felt were being ignored in brain research, including how the brain and the immune system communicate.
The Molofsky Lab is doing innovative research to define how the immune system impacts the brain. Its scientists also are researching the links between immune function and neurological and psychiatric disorders, including post-viral neurological syndromes. Their latest discoveries are bringing them one step closer to developing new treatments for neuropsychiatric diseases.
"Being named a Bowes Biomedical Investigator is such an honor because it allows me to really take risks to try a kind of science that might not have payoffs for many years, and to venture in new directions," Molofsky says.
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Her family immigrated to the U.S. from Brazil when Molofsky was a child. She fell in love with science at the University of Michigan, where her research in stem cell research sparked a fascination with the brain's regenerative abilities. This led her to pursue a PhD in stem cell biology and specialize in psychiatry.
While she was in medical school, Molofsky met her now-husband, immunologist Ari Molofsky , MD, PhD. In 2007, the couple joined UCSF because "it has one of the best neuroscience programs in the country, with people studying brain diseases at the highest level, and one of the leading immunology programs in the country," Anna Victoria Molofsky says. (Ari Molofsky is now a professor in the Department of Laboratory Medicine.)
After Molofsky completed her psychiatry residency at UCSF, she pursued postdoc work studying glial cells with David Rowitch , MD, PhD, a professor in the Department of Pediatrics. Later, when she set up her own lab, researchers were using antibody therapies developed from immune molecules to treat and cure diseases, including cancer and rheumatoid arthritis. Molofsky wondered why these therapies weren't being applied to psychiatric diseases as well.
"If we can understand how these immune molecules influence the brain, maybe we can harness them for therapeutic benefit," she says.
The physician-scientist stresses that her work is not done in isolation.
"UCSF is just a phenomenal place for collaborative research," Molofsky says. "It's expected that you'll work together, and all of the work that I've done has relied on collaborations." She added that she is collaborating with Kampmann, the other 2025 Bowes Biomedical Investigator, on a study of human cells.
Three far-reaching discoveries
Molofsky's collaborations with her husband's lab have led to three discoveries with far-reaching implications.
The first is that the immune signal interleukin-33, a well-known contributor to asthma, is necessary for the brain to develop its synaptic connections and to form memories.
Anna Molofsky's lab also has shown that this molecule helps prevent Alzheimer's disease symptoms in a mouse model.
The second is that another immune signal, interleukin-13, helps inhibitory synapses form in the brain. Molofsky believes that if more of those kinds of synapses are encouraged to form, it might lead to treatments for developmental diseases such as epilepsy.
Molofsky is particularly excited about the third discovery: that interferon, the immune signal that's stimulated in the body with a virus such as a cold or influenza, plays a role in brain development.
As a practicing psychiatrist, Molofsky hopes her work ultimately leads to cures that can help reverse the course of psychiatric diseases such as schizophrenia, bipolar disorder, autism and depression. In the meantime, she focuses on the here and now.
"You can't predict where your work is ultimately going to lead," Molofsky says. "I think the only way to do good science is to have a goal somewhere in your mind - but to be totally immersed in what you're doing at the moment."
Work with Nobel Prize-winning cell biologist
Martin Kampmann, the Dorothy Bronson Professor in the Department of Biochemistry and Biophysics, describes setting up his own UCSF lab in 2015 to study neurodegenerative diseases as a risky move because it was a completely new research area for him: He had most recently been involved in developing and applying advanced genetic screening technologies. However, his scientific curiosity - and an interest in understanding the brain's connection to consciousness, thoughts, and emotions that he'd had since childhood - led him to change his focus.
Traditional funding often is driven incrementally by safe research, and that's the opposite of what we had to do to really break new ground."
While risky, Kampmann says the move also was exciting because it brought cutting-edge technologies and genetics - together with human cells - to the field for the first time. Now his research could lead to the development of new treatments for neurodegenerative diseases such as Alzheimer's. Kampmann's lab is doing groundbreaking work developing and using innovative technologies to understand the cellular and molecular mechanisms of aging-associated neurodegenerative diseases.
The researcher's journey to this point was circuitous. Kampmann found his first course in human biology too descriptive. This realization led him to a program at the University of Cambridge in the U.K. to study molecular and structural biology. "I thought this was a more rejectionist approach where I could ultimately really understand the molecular details of a process," he says.
Working with Nobel Prize-winning cell biologist Günter Blobel while earning his doctorate at Rockefeller University in New York got Kampmann thinking about putting the interactions of molecules into the context of the cell. That work ignited his interest in working his way back up to more complex systems.
Kampmann then wanted to complement his biochemistry and biophysics expertise with genetics. In 2010, he joined the former UCSF lab of Jonathan Weissman, PhD, citing Weissman's work developing new genetic tools for yeast to understand how different factors act together in cells. "I was excited at that point to say, 'Let's do this in human cells,'" he says.
A risky endeavor
Part of the reason Kampmann accepted a faculty position at UCSF was because of the open, collaborative environment. "To change fields completely and start working in a new field the day I started my own lab, I think that would only have been successful at very few places, and UCSF is one of them," he says.
In 2015, the neurodegeneration field had been focused on a small number of hypotheses and a small number of mechanisms or potential therapeutic strategies. As a post-doc in Weissman's lab, Kampmann brought these CRISPR-based screen approaches with cell types relevant to the human brain to the field. Combining the new technologies with genetic screening enabled the team to take completely unbiased, innovative approaches, which uncovered new factors that appear to be important for how some neurodegenerative diseases progress.
Kampmann is grateful for the Bowes Biomedical Investigator Award because it will allow his team to continue high-risk, high-reward research. "Starting out to set up a completely new method is a risky endeavor," he says. "You spend years getting an extremely challenging method to work before you actually have anything to show for it or get any results. Traditional funding often is driven incrementally by safe research, and that's the opposite of what we had to do to really break new ground."
The ultimate goal of his research is to develop new therapies targeting Alzheimer's and other neurodegenerative diseases at the molecular level. And while he acknowledges that the path from scientific discovery to therapy can be quite long, Kampmann remains enthusiastic.
"It's something my team and I are very excited and passionate about," he says.
