Six Stanford researchers receive NIH High-Risk, High-Reward grants

Six Stanford scientists have been awarded grants from the National Institutes of Health (NIH) that recognize unconventional, boundary-pushing work focused on challenges in biomedical and behavioral research.

The six researchers who received grants this year are Andrew Beel, a postdoctoral scholar in the Department of Structural Biology in the Stanford School of Medicine; Michael Fischbach, associate professor of bioengineering in the School of Engineering and the School of Medicine, and of microbiology and immunology in the School of Medicine; Chris Garcia, professor of molecular and cellular physiology and of structural biology in the School of Medicine; Sherri Rose, associate professor of health policy in the Freeman Spogli Institute for International Studies and the School of Medicine; Serena Sanulli, associate professor of genetics in the School of Medicine; and Mark Skylar-Scott, assistant professor of bioengineering in the School of Engineering and the School of Medicine.

The High-Risk, High-Reward Research Program is part of the NIH Common Fund, which, according to the NIH’s press release, oversees programs that “pursue major scientific opportunities and gaps throughout the research enterprise, are of significant importance to NIH, and require collaborations across the agency to succeed.” The goal is to encourage investigators to work on research that may otherwise face difficulties getting funded in more traditional ways. This year, the NIH program has awarded 103 grants totaling about $285 million over five years.

Pioneer Award

Sherri Rose received the NIH Director’s Pioneer Award, which was established to provide funding for investigators at all career levels with bold and innovative research projects. She will use it to delve deeper into her research about the potential harms of health care algorithms on marginalized groups.

Algorithms are pervasive in society, and when used for decision-making in the health care system they can lead to poorer health outcomes and lack of access to care.

“These algorithms impact the lives of millions of patients but are not rigorously evaluated for systematic harms before they are implemented,” Rose said. “It’s empowering to have the opportunity to build a broad, interdisciplinary, and inclusive team to begin to tackle designing a framework for the social impact of algorithms.”

Rose, co-director of the Health Policy Data Science Lab, will use the $5.5 million award to develop complex causal network models by harnessing her expertise in machine learning, ethical AI, health economics, health policy, and statistics.

She intends to create a novel social impact framework to transform the development and application of algorithms in health care, “establishing a blueprint where tools are routinely evaluated for social impact before deployment.”

New Innovator Award

The New Innovator Award funds innovative research by investigators who are within 10 years of having earned postgraduate degrees or finished clinical residencies and who have not yet received research funding from the NIH.

Serena Sanulli’s lab studies the structure and biophysical properties of chromatin, which is the physiological matrix of our genome. Her New Innovator Award will support their efforts to investigate the structural plasticity of nucleosomes, the fundamental regulatory unit of chromatin. Contrary to previous assumptions, the Sanulli lab recently discovered that the core of the nucleosome is malleable, and that this structural flexibility regulates genome architecture – suggesting that shape-shifting nucleosomes might represent a hub for genetic and epigenetic regulation, as well as a potential therapeutic target.

“Recent discoveries have brought a completely new lens through which to think about genome regulatory processes and generated exciting novel hypotheses,” said Sanulli, who is also a member of Stanford Bio-X and a faculty fellow of Sarafan ChEM-H. “I am excited to explore these novel conceptualizations and their implications for both fundamental and translational research.”

Sanulli and her lab will work toward developing novel tools to interrogate and manipulate chromatin atomic-scale structures, pursuing both structural and functional studies. This work will enable them to expand the fundamental understanding of chromatin regulation and its role in biology.

Mark Skylar-Scott and his laboratory aim to realize the dream of 3D-bioprinted organs on-demand, which could help end donor organ scarcity.

“Approximately 1 in 100 children are born in the US with congenital heart defects,” said Skylar-Scott, who is also a member of Bio-X, the Cardiovascular Institute, and the Wu Tsai Neurosciences Institute. “For the most severe defects, such as patients with single ventricle disease, the creation of new patient specific tissue offers a healthy and normal life span. However, practicing tissue engineering at this scale has been prohibitively expensive for research labs.”

This lab’s approach combines large-scale stem cell culture with high-throughput bioprinting to assemble cells and blood vessels to form thick, viable, and functional tissue.

“With our New Innovator Award, we aim to reduce the cost of stem cell culture to accelerate organ scale engineering research,” said Skylar-Scott, estimating that this work could reduce the cost of stem cell culture and differentiation to nearly 1/100th the current cost

Transformative Research Award

This award supports individuals or teams proposing projects that are inherently risky and untested, but that have the potential to create new paradigms. It aims to promote cross-cutting, interdisciplinary approaches and is open to individuals and teams of investigators.

Michael Fischbach will use his Transformative Research Award to develop new kinds of vaccines that leverage the microbiome – the collection of bacteria that live on and inside humans.

Traditional vaccines work by training the immune system to recognize molecules on the surface of pathogens, like viruses. Certain kinds of bacteria in the skin microbiome are known to trigger a strong immune response, and Fischbach hopes to engineer those bacteria to steer the immune system to more strongly and selectively hit its target. This platform could lead to new vaccines not only for viruses but also for cancers and autoimmune disorders.

Engineering bacteria to produce specific molecules is a goal of many scientists like Fischbach, who is also the director of the Microbiome Therapies Initiative, a Stanford initiative dedicated to building microbial communities that can be used as medicines.

“Microbial colonists elicit potent and specific immune responses,” said Fischbach, who is an Institute Scholar at Sarafan ChEM-H and a member of Bio-X and the Wu Tsai Human Performance Alliance. “We are excited to explore whether we can redirect this response to create vaccines for cancer and infectious disease.”

Chris Garcia will use his award to accelerate research on a global map of interactions among human cell-surface proteins and secreted ligands (substances that bind to proteins, often altering the way those proteins work).

This map will have a major impact on biomedical research, according to Garcia, because cell-cell interactions mediated by cell-surface proteins are central to human physiology, controlling almost every biological process that is affected by disease. These proteins and secreted ligands comprise the majority of the therapeutic drugs that have been developed in recent years.

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

Early Independence Award

Andrew Beel, a postdoctoral scholar and former graduate student in the laboratory of Roger Kornberg, professor of structural biology, received a NIH Director’s Early Independence Award, which aims to encourage “exceptional junior scientists” to pursue independent research. Beel will use the funds he received from the award to start a research group in the Department of Structural Biology.

“Without this award, I would not have been able to start my own group,” said Beel, whose research program will concentrate on the axial core of the mitotic chromosome, the classic X-like structure a chromosome assumes when the cell containing it undergoes mitosis, a type of cell division. The existence of such a core has been noted since the second half of the 20th century but what it looks like and how it works are still shrouded in mystery.

“We aim to bring the tools of biochemistry and structural biology to bear on the mitotic chromosome’s core to better characterize its composition, structure, and function,” Beel said.

Chromosomal structure in mitotic cells is of particular importance when those cells are dividing abnormally, as happens in cancer.

“We also aim to develop small-molecule modulators targeting this core region, which will be useful in dissecting the pathways responsible for its assembly and disassembly, and may also prove therapeutically useful in oncology.”

Alexander Gitlin, a former instructor in the Department of Pathology in the School of Medicine also received an Early Independence Award. He is now at the Sloan Kettering Institute.