John Hancock
University of Texas Health Science Center at Houston, TX·Biochemistry
KRAS is a protein that acts as an on/off switch for cell growth, survival and specialization. When mutated, it is stuck in the "on" state and drives many cancers.
- Fields
Biochemistry
Biophysics
Pharmacology
- Topics
oncogenes
cancer biology
plasma membrane
- Grants
- 1 known grant, through Jun 2027
What they work on
- Test whether glycosphingolipids act as spatial organizers of the inner plasma membrane and ER-plasma membrane contact sites, using lipid biosensors and high-resolution imaging.
- Probe how outer-surface glycosphingolipids couple to the inner-surface lipid phosphatidylserine, using genetic approaches, lipid reconstitution experiments and molecular dynamics simulations.
- Test whether this glycosphingolipid-based control of KRAS membrane localization matters for cancer growth in multiple mouse KRAS cancer models.
More about the research
To work, active KRAS must sit on the inner face of the cell's outer membrane, called the plasma membrane, in the right mix of lipids. Cancer cells with mutant KRAS rely heavily on aerobic glycolysis, a sugar-burning metabolism known as the Warburg effect. The team found that this glycolysis produces a set of glycosphingolipids (GSLs), sugar-coated lipids on the outer surface of the membrane, and that these lipids control whether KRAS stays at the membrane. Blocking GSL production by removing glucose, using drugs, or deleting key enzymes pulled KRAS off the membrane. Deleting key GSL-making enzymes also stopped KRAS-driven cancer in cell culture and in animals.
Why it matters
Mutant KRAS drives many cancers and must sit on the cell membrane in the right lipid setting to work. Showing how surface glycosphingolipid metabolism keeps KRAS in place could reveal a new weak point in KRAS-driven tumors. That weak point might be targeted therapeutically. The work also adds basic understanding of how the two layers of the cell membrane coordinate their lipids.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Peter J Tontonoz
University of California-Los Angeles, CA·Physiology
Define how IL-22 from gut T cells suppresses fatty-acid uptake by intestinal cells, using genetic mouse models, chemical inhibitors and intestinal enteroids (lab-grown mini-intestines).
Anant Menon
Weill Medical College of Cornell University, NY·Biochemistry
Determine how newly discovered phospholipid scramblases in the outer mitochondrial membrane move lipids, and define their contributions to mitochondrial growth and biogenesis, using a multidisciplinary suite of methods.
Mohamed Trebak
University of Pittsburgh, PA·Physiology
Determine how native ORAI1–3 calcium channels and STIM1/STIM2 ER calcium sensors move, associate, dissociate and are internalized at PM–ER junctions.
The school
University of Texas Health Science Center at Houston: 25 labs on PI Pages, $419M a year on research, 340 research doctorates a year.
More about University of Texas Health Science Center at Houston
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