Britta Will
Albert Einstein College of Medicine, NY·Biology
As we age, the stem cells that make our blood slowly change. In some people, these altered stem cells eventually give rise to blood cancers.
- Fields
Biology
Medicine & Clinical Research
Biochemistry
- Topics
chaperone-mediated autophagy
hematopoietic stem cells
leukemic stem cells
- Grants
- 2 known grants, through Jun 2029
What they work on
- Map when chaperone-mediated autophagy (CMA), a selective protein-recycling pathway, is active in precancerous CHIP blood stem cells and leukemic stem cells, using a CMA reporter mouse and lentiviral CMA biosensors in patient cells.
- Test whether loss of CMA lets blood stem cells carrying CHIP mutations expand, using new genetic mouse models in which CMA is inactivated.
- Test whether leukemic stem cells need CMA to survive amino acid starvation by recycling lysosomal cysteine into coenzyme A for fatty acid production, using mouse models, human cell lines and primary patient cells.
- Determine the molecular and functional effects of switching CMA off or stimulating it in leukemic stem cells, to judge whether CMA could be a therapeutic target in myeloid cancers.
More about the research
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are two such cancers. They mostly strike older adults, and fewer than 30% of patients are cured. Often they follow years of a hidden precancerous stage called clonal hematopoiesis of indeterminate potential (CHIP). In CHIP, blood stem cells carrying certain mutations quietly expand. What separates normal stem cell aging from the path to cancer is poorly understood. The lab's main project tackles this question by studying a cellular recycling system. The lab is also part of a cancer center research program on how cancer stem cells evolve and resist therapy.
Why it matters
MDS and AML are largely incurable, and overall cure rates have stayed below 30% for decades. Finding how chaperone-mediated autophagy separates healthy aged blood stem cells from leukemic stem cells could point to ways of targeting autophagy in these cancers. Such approaches could help patients with MDS and AML, and the same principles might apply to other stem cell–derived cancers.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Wei Du
University of Pittsburgh, PA·Medicine & Clinical Research
Examine how TREM1, a stress-induced immune receptor, acts within leukemia-associated macrophages during leukemia development, using inducible macrophage-specific Trem1 knockout mice in Fanca-deficient and MLL-AF9 leukemia models.
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.
Lukasz Gondek
Johns Hopkins University, MD·Medicine & Clinical Research
Determine the cancer-causing potential of donor-derived CHIP in transplant recipients, using a cohort of 1,857 donors over 40 and serial recipient samples to separate true driver mutations from background aging mutations.
The school
Albert Einstein College of Medicine: 21 labs on PI Pages, $361M a year on research, 36 research doctorates a year.
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