Dustin Maly
University of Washington, WA·Biochemistry
Protein kinases are enzymes that switch other proteins on or off by attaching phosphate groups. They are major drug targets in cancer and chronic inflammation.
- Fields
Biochemistry
Chemistry
Pharmacology
- Topics
protein kinases
Raf kinases
RAS signaling
- Grants
- 2 known grants, through Jul 2029
What they work on
- 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.
- Perform deep mutational scans of Raf versions, using the lab's RNA barcoding method, to map how mutations affect Raf structure, function and drug response.
- Analyze how upstream and downstream modulators of Raf signaling change the activity of Raf kinases and their interactions with partner proteins inside cells.
- Profile the internal and external regulation of Lck, a Src-family kinase essential for T cell receptor signaling, to find what sets it apart, using enzymology, biochemistry and chemoproteomics.
- Develop a new technology to profile the regulatory and shape states of kinases during T cell receptor signaling, and test the effects of altering Lck's controls.
More about the research
Yet even well-studied kinases still hide surprises about how they are controlled inside cells. The lab builds new chemical tools to probe how kinases are regulated, which shapes they adopt and which partner proteins they bind. It then uses these tools to learn how those features control what kinases do. Two projects apply this strategy to different kinase families.
Why it matters
Mis-regulated Raf kinases drive many RAS- and Raf-mutant cancers. Understanding why these kinases resist certain inhibitors may help design more effective cancer therapies. Learning how kinase active-site shapes and Lck regulation control signaling could inform new drugs for cancer and chronic inflammatory diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jason Zhang
University of California-Los Angeles, CA·Biochemistry·Early-career
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.
Adam Courtney
University of Michigan, MI·Microbiology & Immunology
Determine how negative feedback loops, in which activated kinases (enzymes that add phosphate tags) dampen their own pathway, shape distinct T cell receptor signaling outcomes, using chemical tools and immunological assays.
Amy Barrios
University of Utah, UT·Biochemistry
Develop fluorogenic peptide substrates, molecules that fluoresce when cut by an enzyme, that are selective for LAR receptor tyrosine phosphatases, using sequences of their known biological targets, and validate them for use in cells.
The school
University of Washington: 81 labs on PI Pages, $1.7B a year on research, 694 research doctorates a year.
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