Six Chan Zuckerberg Biohub Investigators representing all three of our partner universities are among the 2022 grantees of the High-Risk, High-Reward Program of the National Institutes of Health (NIH) announced in October. These grants provide support for “exceptionally creative scientists pursuing highly innovative research with the potential for broad impact in biomedical, behavioral, or social sciences,” according to the NIH.

All told, the NIH made 106 High-Risk, High-Reward grants this year, totaling approximately $329 million over five years. In announcing this year’s recipients, NIH Director Francis S. Collins said, “The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known. These visionary investigators come from a wide breadth of career stages and show that groundbreaking science can happen at any career level given the right opportunity.”

Transformative Research Awards

Stanford University’s Michael Fischbach and UC San Francisco’s Hani Goodarzi each received NIH Director’s Transformative Research Awards. Open to scientists at any career stage, these awards have flexible budgets to support research projects “that are inherently risky and untested but have the potential to create or overturn fundamental paradigms.”

An associate professor in the Departments of Bioengineering and of Microbiology & Immunology at Stanford, Fischbach is also an Institute Scholar of Stanford’s Sarafan ChEM-H program, and director of the Stanford Microbiome Therapies Initiative. In recent work Fischbach and colleagues discovered that commensal bacteria that colonize our bodies induce a robust response in the T cells of the immune system. In the project supported by the NIH Director’s award, his lab will explore how these bacteria might be engineered to mount an immune response that could target cancer.

Goodarzi, associate professor of biochemistry and biophysics at UCSF, shares his award with Principal Investigator Justin Ichida, the John Douglas French Alzheimer’s Foundation Associate Professor of Stem Cell Biology and Regenerative Medicine at the University of Southern California. With the new award, Goodarzi and Ichida will adapt a platform they designed for cancer drug discovery, using induced pluripotent stem cells (iPSCs) obtained from patients with amyotrophic lateral sclerosis, or ALS. There is considerable clinical heterogeneity among patients with ALS, and using their platform the researchers hope to find new drug targets that could either help a broad range of patients or point the way to patient-specific therapies.

New Innovator Awards

NIH Director’s New Innovator Awards, which provide $1.5 million in research funds over two years to early-career scientists pursing “innovative, high-impact projects,” went to Yvette Fisher of UC Berkeley; UC San Francisco’s Emily Goldberg; and Serena Sanulli and Mark Skylar-Scott, both of Stanford.

In her Berkeley lab, Fisher, assistant professor of neurobiology in the Department of Molecular and Cell Biology, uses genetic, electrophysiological, and imaging techniques to study the brain circuitry involved in navigation in the fruit fly Drosophila melanogaster. She aims to better understand how neural circuits change their computations to adapt to different conditions.

Goldberg, an assistant professor in UCSF’s Department of Physiology, studies the interrelations of immunity and metabolism. With her new NIH award, she will study immune cells that reside within body fat (adipose tissue), which combat cellular stress and reduce inflammation. With age these immune cells become dysregulated, and Goldberg and her team will search for ways to retore their normal function.

Sanulli and colleagues recently discovered that nucleosomes, the molecular spools around which DNA is wound to pack it tightly into cell nuclei, have a flexible core that can exert effects on genome architecture and function. With the new NIH award, she and her team will develop nanobodies that can detect conformational changes in nucleosomes to further understand their role in genome regulation.

Skylar-Scott aspires to build “trillion-cell cultures” of iPSCs to support the creation of cardiac organoids that recapitulate the cellular makeup of components of the human heart. These organoids could eventually serve as “ink” for 3D bioprinted cardiac ventricles to replace damaged ventricles in cases of heart failure.