Diane Barber
University of California-San Francisco, CA·Biochemistry
Cancer cells are slightly less acidic inside than normal adult cells. This higher intracellular pH (pHi) helps cancers progress, but how it changes cell behavior is poorly understood.
- Fields
Biochemistry
Biology
Biophysics
- Topics
intracellular pH
pHi
cancer biology
- Grants
- 1 known grant, through Mar 2028
What they work on
- Test whether changes in intracellular pH alter how transcription factors FOXC2, SOX4 and MAX pick DNA targets, by protonating a DNA-contacting histidine, measuring binding to known DNA motifs.
- Map pH-dependent genome-wide DNA binding of these transcription factors and test their pH-regulated binding selectivity inside cancer cells.
- Test whether targeting the nucleotide-binding histidine in transcription factors can reactivate a tumor suppressor pathway in cancer cells.
- Determine whether varying intracellular pH marks distinct cell types in colorectal cancer spheroids and patient-derived organoids, using single-cell RNA-seq and genetically altered pH.
- Track intracellular pH changes as tumors form in living Drosophila, using a fly line that expresses a genetically encoded pH biosensor.
More about the research
The lab links protein electrostatics, the way electric charges on proteins shape their behavior, to cell biology. In earlier work, the team identified ways pHi drives tumor formation and changes cell metabolism. It also showed how cancer mutations that change a protein's charge can promote cancer, and how pHi shifts control proteins binding lipids and other proteins. This renewal asks two new questions: can pH control which genes are turned on, and do differences in pH between cells in a tumor mark different cell types?
Why it matters
Targeting features unique to cancer cells could slow metastasis with fewer side effects on healthy tissue. Showing how high internal pH steers gene activity and tumor cell variety may point to new ways to limit cancer metabolism and growth across tissue types and genetic backgrounds. It could also show how measuring cancer cell pH can predict outcomes or deliver drugs selectively.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
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The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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