Jason Zhang
University of California-Los Angeles, CA·Biochemistry·Early-career
Ras proteins act as on-off switches that tell cells to grow. Mutations that lock Ras in the on position drive about a third of all cancers.
- Fields
Biochemistry
Biomedical Engineering
Pharmacology
- Topics
Ras
drug resistance
oncogenic signaling
- Grants
- 1 known grant, through Aug 2028
What they work on
- Develop Ras activity sensors further and apply them in complex cancer cell models, beyond flat 2D culture, to track where in the cell Ras is switched on during Ras inhibitor treatment.
- Use de novo protein design to build sensors, proximity labelers and perturbation tools selective for individual Ras isoforms, the four closely related forms of the Ras protein.
- Test whether normal (wild-type) Ras activity on internal membranes compensates for inhibited mutant Ras across inhibitors of RasG12C, G12D, G12R and G12S, using microscopy and proteomics to find the proteins driving resistance.
More about the research
Drugs that block one mutant form, RasG12C, now exist, but most patients who take them relapse. Their tumors find a way to switch Ras signaling back on, and how they do this is unknown. Understanding this escape route could reveal new ways to keep Ras-driven cancers from becoming drug resistant.
Why it matters
Resistance limits the benefit of new Ras-blocking drugs for the many patients whose cancers are driven by Ras mutations. Identifying how cancer cells reactivate Ras signaling during treatment could point to new therapeutic targets for overcoming resistance. The Ras sensors and isoform-specific tools developed here may also serve the wider cancer research community, with possible uses in diagnostics and therapeutics.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dustin Maly
University of Washington, WA·Biochemistry
Define the pathways that make A-, B- and C-Raf kinases sensitive or resistant to specific classes of ATP-competitive inhibitors and co-inhibition strategies, using a suite of molecular tools.
Wantong Yao
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Define the molecular pathways through which a newly identified stress-response regulator helps pancreatic ductal adenocarcinoma (PDAC) cells survive nutrient shortage, low oxygen and oxidative stress, and evade the immune system.
Kenneth Olive
Columbia University, NY·Pharmacology
Trace how genetic resistance to pan-RAS inhibitors such as RMC-7977 evolves in pancreatic tumors, including MYC copy number gains, using mouse and human models and clinical trial samples, and identify new vulnerabilities it creates.
The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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