Luisa Cimmino
University of Miami, FL·Pharmacology
Acute myeloid leukemia (AML) is a blood cancer that mostly affects older adults. Many patients cannot tolerate aggressive chemotherapy, so survival is poor and gentler treatments are badly needed.
- Fields
Pharmacology
Medicine & Clinical Research
Genetics
- Topics
acute myeloid leukemia
hematological malignancy
vitamin C
- Grants
- 1 known grant, through Jul 2028
What they work on
- Determine how physiological versus high pharmacological doses of ascorbate (vitamin C) change the activity of TET enzymes, which remove methyl tags from DNA, in acute myeloid leukemia cells.
- Test whether uptake through sodium-dependent vitamin C transporters, or the amount of TET activity remaining in TET2-mutant AML cells, determines how well ascorbate treatment works.
- Test whether AML driven by TET2 mutation and different cancer-causing genes is sensitive to ascorbate combined with standard AML chemotherapy.
- Design rational drug combinations that use ascorbate as an add-on therapy, guided by data from the lab's loss-of-function genetic screens in AML cells.
- Increase ascorbate's availability as a TET2 cofactor using fat-soluble (lipophilic) ascorbyl analogs and genetic or drug-based changes to vitamin C transporters on AML cells.
More about the research
One candidate is vitamin C (ascorbate). Besides acting as an antioxidant, ascorbate is a helper molecule (cofactor) for TET enzymes. These enzymes remove chemical methyl tags from DNA and so reactivate silenced genes. One of them, TET2, acts as a tumor suppressor in blood cells. Loss-of-function mutations in TET2 are common in AML and linked to worse outcomes. These mutations usually hit only one of a patient's two copies of TET2, so boosting the remaining healthy copy could be a treatment strategy.
Why it matters
Older adults with acute myeloid leukemia who cannot withstand intensive chemotherapy could benefit from a non-toxic add-on therapy. This is especially true for patients whose leukemia carries TET2 mutations. By identifying the doses, leukemia types and drug partners where vitamin C works best, and ways to boost its uptake, the work aims to lay the groundwork for clinical testing of vitamin C combined with existing AML treatments.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Boaz Tirosh
Case Western Reserve University, OH·Pharmacology
Map the specific defect in mitochondrial respiration that appears when AML cells are treated with the mTORC1 activator AcTor plus a proteasome inhibitor, a drug that blocks protein disposal.
Xunlei Kang
University of Missouri-Columbia, MO·Medicine & Clinical Research
Determine how DPP4, a cell-surface enzyme, controls the location, survival and self-renewal of human AML stem cells, using colony-forming assays and mice carrying human AML cells.
Ravindra Majeti
Stanford University, CA·Genetics
Determine how long the pre-leukemic phase lasts in people who progress to acute myeloid leukemia, and whether that duration affects how the disease develops.
The school
University of Miami: 30 labs on PI Pages, $559M a year on research, 297 research doctorates a year.
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