NIH High-Risk, High-Reward grants awarded to Stanford researchers

Editor’s note: An earlier version of this story omitted mention of the fourth Stanford awardee, Robbie Majzner.

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

From left to right: Robbie Majzner, Monther Abu-Remaileh, Yonatan Winetraub and Maya Kasowski. (Image credit: Steve Fisch/Malik Abu-Remaileh/ Andria Grodzinsky/Norman L. Cyr)

The four researchers who received grants this year are Monther Abu-Remaileh, assistant professor of chemical engineering, Maya Kasowski, assistant professor of medicine and of pathology, Robbie Majzner, assistant professor of pediatrics, and Yonatan Winetraub, an instructor in 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 opportunities and gaps throughout the research enterprise that are of great importance to NIH and require collaboration across the agency to succeed.” The goal is to encourage investigators to pursue research that may otherwise face difficulties getting funded in more traditional ways. This year, the NIH program has awarded 106 grants totaling about $329 million over five years.

Early Independence Award

Yonatan Winetraub received an NIH Director’s Early Independence Award, which aims to encourage “exceptional junior scientists” to pursue independent research and provides $250,000 per year for up to five years. He earned his doctorate in biophysics from Stanford in 2021, was a Bio-X Bowes fellow and started his own lab at Stanford this fall.

Winetraub’s research focuses on utilizing Optical Coherence Tomography and machine learning to image cancer non-invasively at a single-cell resolution. Currently, detecting most solid cancers and confirming the boundaries – or margins – of the tumor often entails analyzing chemically stained sections of tissue that are obtained via biopsy. Winetraub and members of the de la Zerda group at Stanford have recently developed a virtual version of this process. The NIH award will support further work on this project.

“This imaging modality provides real-time diagnosis of tumor margins and invasiveness by scanning a large tissue area for residual cancer cells. Such information would guide treatment decisions for diseases such as brain and skin cancer,” said Winetraub. “Essentially, we are scanning tumors without biopsies, saving patients valuable time in learning results and saving medical expenses and unnecessary pain and scarring.”

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 research funding from the NIH.

Monther Abu-Remaileh will use his New Innovator Award to continue his studies of the biochemical functions of lysosomes – cellular organelles known for their remarkable digestive abilities, which enable them to perform various important roles, including cleaning, repairing and protecting the cell. Broadly, the Abu-Remaileh Lab seeks to understand how lysosomes communicate with other parts of the cell under different metabolic conditions and how lysosome dysfunction relates to disease.

“This grant will support our efforts to determine the role of the lysosome in metabolic adaptation by studying its function in metabolic rewiring of KRAS-driven cancers,” said Abu-Remaileh, who is also an Institute Scholar of Stanford ChEM-H. Cancers that are linked to the KRAS gene include some types of non-small cell lung cancer, colorectal cancer and pancreatic cancer. In many of these cancers, and others, lysosomes are essential to the survival and growth of cancer cells.

“This work has the potential to identify metabolic vulnerabilities that can be exploited as novel therapeutic targets in these fatal diseases,” said Abu-Remaileh.

Maya Kasowski, who was also awarded a New Innovator Award, will use her award to investigate the genetics of food allergies and other allergic disorders.

“There is a rising incidence of allergic disorders worldwide,” Kasowski said. “Although it’s clear that one’s environment plays a role in the development of allergies, studies of identical twins indicate that our genes are also important.”

Kasowski’s laboratory studies how immune cells grown in the laboratory react to the presence of allergens to map the molecular basis of food allergies. “We plan to use this powerful system to pinpoint genetic variants that make some individuals susceptible to the environmental factors that cause allergic disorders,” she said.

Robbie Majzner will use his New Innovator Award to study how to make a potent form of cancer immunotherapy more useful. The therapy, consisting of engineered immune cells called CAR-T cells, targets surface markers unique to cancerous cells, flagging them for destruction. The approach has greatly improved survival rates for patients with certain blood cancers since it received approval from the Food and Drug Administration in 2017, but it cannot be used for most solid tumors.

“In their current form, CAR-T cells are unsafe for patients with many solid tumors because the surface markers on these tumors are widely shared with healthy tissues,” Majzner said. If CAR-T cells are designed to respond to most single solid-tumor markers, they would also attack healthy organs, causing dangerous side effects.

To address the problem, Majzner’s team developed a novel mechanism that activates CAR-T cells only when several tumor markers are present, allowing the cells to recognize tumors and leave healthy tissue alone. “We hope this work will open the door to effective and powerful immunotherapy for solid tumors,” Majzner said.