S. John Liu, MD, PhD, an assistant professor of Radiation Oncology and Neurological Surgery at UC San Francisco, has been named one of the three recipients of this year’s Distinguished Scientist Award (DSA) from the Sontag Foundation.
The $750,000 funding award is among the most prestigious honors for early-career investigators and supports his lab’s research using new functional genomic techniques to find better therapies for glioblastoma.
“We are proud to recognize Dr. John Liu as a DSA recipient. His research strengthens the scientific depth of the DSA program, and it is our privilege to support John on this important project,” said Hilary Keeley, the executive director of the Sontag Foundation. “We look forward to seeing how his work accelerates progress for patients facing a brain tumor diagnosis.”
Glioblastomas are challenging to treat in part because they are made up of many different types of cells that often respond to therapy in ways that can be difficult to predict from traditional cell culture models.
Liu, who is also a practicing radiation oncologist at UCSF, seeks to better understand the genes regulating radiotherapy response within the context of the whole tumor and its surrounding environment.
“This DSA-funded research project will uniquely reveal how gene disruptions in tumor and immune cells reprogram how the cells interact with each other, offering new avenues to intervene for next-generation glioblastoma therapeutics,” he said.
Liu and his research group recently showed that they can combine the high-throughput capacity of CRISPR screens with the precision of single cell RNA sequencing in models of glioblastoma to assess how each individual genetic perturbation affects responses to treatments such as radiation therapy. This approach, which is known as in vivo Perturb-seq, has helped them identify genetic vulnerabilities that could make the tumors more sensitive to radiotherapy. His group also showed that epigenetic editing using engineered CRISPR systems can directly sensitize glioblastoma to therapy, offering a way to target these vulnerabilities.
For example, one such promising target is the PRKDC gene, which encodes an enzyme that regulates a cell’s response to DNA damage. Liu has shown that, in glioblastoma, inhibiting this protein upregulates genes involved in the immune response. By further studying this protein’s role in the tumor microenvironment, Liu’s work could identify new strategies for stimulating the immune system to more effectively destroy the tumor cells.
His lab in the UCSF Brain Tumor Center is now also examining how genetic perturbations in the tumor cells then affect their interactions with the many other cells within the tumor using custom-designed spatial profiling. This technology allows researchers to map the location where gene expression changes are happening within a tissue sample.
“Ultimately, we envision these approaches as a way to more rapidly move discoveries we make in the laboratory to treatments for actual people,” he said.
Liu was the 2022 ASCO Conquer Cancer Foundation-Sontag Foundation Young Investigator Award (YIA) winner. He is the first ASCO Conquer Cancer Foundation- Sontag Foundation YIA winner to receive a DSA. His ASCO YIA-funded project serves as a portion of the preclinical support for his DSA project.
He is now the fourth scientist from UCSF to receive this award from the Sontag Foundation since its inception in 2003, joining a group of exceptional colleagues and collaborators.
“I’ve had the great fortune of being mentored by and working with several previous Sontag DSA awardees,” Liu said. “To me, this community represents such a vibrant group of individuals who are united by the mission of ending brain cancer.”
UCSF has consistently ranked among the top two neurology and neurosurgery programs in the country over the last eight years. The UCSF Brain Tumor Center is one of the largest comprehensive programs in the country dedicated to providing the most advanced care for brain and spinal tumors.