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High-risk, high-reward grants awarded to four Stanford researchers

Wu Tsai Neurosciences Institute, Stanford University

Four Stanford researchers have received High-Risk, High-Reward Research grants from the National Institutes of Health

The researchers will receive grants totaling $10 million to fund their investigations. The awards support risky efforts that could potentially have a big impact in the biomedical and behavioral sciences. 

“The NIH’s continuing drive to fund creative research will lead to entirely new concepts and whole new approaches to understanding disease and wellness,” said Lloyd Minor, MD, dean of the School of Medicine. “As our visionary and talented Stanford Medicine scientists further our precision health vision, society will reap profound benefits in the form of breakthrough therapies, preventive measures and minimization of side effects through precisely tailored interventions.”

This year, the NIH issued 85 awards totaling $251 million.

“The breadth of innovative science put forth by the 2020 cohort of early career and seasoned investigators is impressive and inspiring,” said NIH Director Francis Collins, MD, PhD. “I am confident that their work will propel biomedical and behavioral research and lead to improvements in human health.”

Two of the Stanford scientists received Pioneer Awards, and two received New Innovator Awards. 

Pioneer Award

The Pioneer Award provides up to $3.5 million over five years to investigators at all career levels to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical or behavioral science.

Annelise Barron

Annelise Barron, PhD, the W.M. Keck Associate Professor of Bioengineering, will receive $3.5 million over five years. She intends to use the funding to explore a novel mechanism of sporadic Alzheimer’s disease and to demonstrate a method of preventing and treating it in a safe, cost-effective way.

“The prevalence of Alzheimer’s disease in the United States and the world is on the rise, with commensurate tolls on our medical-care system and the economy,” Barron said. “Some 6 million Americans, and more than 42 million people worldwide, currently suffer from this disease.” 

Barron will investigate the hypothesis that dysregulation of the human innate immune system via the degradation of two proteins, LL-37 and apolipoprotein E, creates susceptibility in a subset of the population to late-onset Alzheimer’s disease associated with brain infections. Barron further hypothesizes that this susceptibility can be prevented and treated via upregulation of the human gene that encodes LL-37. She will perform preclinical studies in mice to investigate these hypotheses.

Barron is a member of Stanford Bio-X, the Stanford Cancer Institute and the Stanford Wu Tsai Neurosciences Institute.

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Peter S. Kim, PhD, the Virginia and D. K. Ludwig Professor of Biochemistry, intends to use his $3.5 million award to develop vaccines that are effective against multiple strains of pathogens, such as influenza and HIV.

These universal vaccines would work by focusing the immune system’s antibody response toward specific regions, or epitopes, of an infectious disease agent. This should, Kim believes, elicit antibodies that neutralize the pathogen’s ability to infect while minimizing production of competing antibodies that could interfere with this process.  The goal is to develop vaccines that target regions of a pathogen that are necessary to its success — and thus highly conserved across its strains — leading to broad-spectrum protection and reducing the possibility of “escape” by mutant variants.

The proposed method involves blocking an epitope with a monoclonal antibody that binds tightly to it; coating adjoining regions of the pathogen with a Teflon-like substance that renders them incapable of triggering an immune response; and finally releasing the blockade of the epitope. 

“If successful, this new approach could be applied broadly for the creation of important, novel vaccine candidates to prevent infectious disease,” Kim said.

Kim is a member of Stanford Bio-X, Stanford Maternal & Child Health Research Institute and the Stanford Wu Tsai Neurosciences Institute and an institute scholar of Stanford ChEM-H.

New Innovator Award

The New Innovator Award provides up to $1.5 million over five years to fund innovative research by investigators who are within 10 years of having earned postgraduate degrees or finished clinical residencies and who have not yet received a research project grant or the equivalent from the NIH.

Keren Haroush

Keren Haroush, PhD, assistant professor of neurobiology, will use her $1.5 million New Innovator award to elucidate the neuronal building blocks that allow us to interact with one another.

“Social interactions clearly have a great impact on our mental health, as witnessed by all of us in their relative absence during this pandemic,” Haroush said. “One in four people suffer from mental health issues during their lives. Yet we have little mechanistic understanding of the underlying neuronal circuits associated with these problems.” 

Social interactions are rich and complex, she said. “We have unique patterns of interactions with each person in our lives. Similarly, neural dynamics are composed of a large number of complex spatio-temporal patterns. Understanding the relationship between the two is highly challenging. But putting these jigsaw puzzle pieces together, understanding how neuronal circuits support specific types of interactions, will be crucial for developing therapies for currently intractable psychiatric and neurological disorders.”

The NIH award, she said, will allow her the freedom to explore this complexity and try out different solutions in search of the most yielding path.

Haroush is a member of Stanford Bio-X, Stanford Maternal & Child Health Research Institute and Stanford Wu Tsai Neurosciences Institute.

Siddhartha Jaiswal

Siddhartha Jaiswal, MD, PhD, assistant professor of pathology, has received a New Innovator Award for $1.5 million. His research focuses on understanding the biology of mutations important to the development of blood cancers and other age-related diseases. As a postdoctoral scholar at the Broad Institute, he identified a pre-malignant state for blood stem cell clones that regulates their blood-forming capabilities. 

“Several years ago, I discovered that cancer-associated mutations are common in the blood of aging humans and predispose them to leukemia, heart disease and early death,” Jaiswal said. “However, our understanding of the causes and consequences of these mutations is incomplete. The funding from this award will allow my lab to explore the links between these mutations and a vast array of other aging-related diseases in hundreds of thousands of people. Our group will also identify the factors that promote the growth of these stem cell clones, which may lead to new therapies that prevent the development of blood cancers or other aging diseases associated with these mutations.”

Jaiswal is a member of the Stanford Cardiovascular Institute, Stanford Cancer Institute, the Stanford Institute for Stem Cell Biology and Regenerative Medicine and Stanford Bio-X.