Amjad Askary
University of California-Los Angeles, CA·Genetics
During development, a cell's fate depends on the history of signals it has received over time. These signals come from a few key pathways, such as BMP, Wnt and Nodal.
- Fields
Genetics
Biology
Biomedical Engineering
- Topics
molecular recording
CRISPR base editing
signaling history
- Grants
- 1 known grant, through Feb 2031
What they work on
- Extend a CRISPR base-editor recorder, which writes signaling activity into DNA, to capture the full range of signal strengths in living tissue and to record the order and timing of two pathways at once.
- Engineer mouse embryonic stem cells to record BMP, Wnt and Nodal signaling, and use embryo models and chimeric embryos to link early signaling to cell fate and position at the onset of organ formation.
- Determine how an initial BMP exposure causes long-term changes in responsiveness without differentiation, using epigenomic assays and quantitative imaging.
- Test whether Wnt and Nodal pathways have similar signaling memory and whether this memory mediates long-term crosstalk between pathways.
More about the research
Usually only the end result can be observed, because tracking signals live in mammalian embryos is impractical. The lab built a molecular recorder that writes signaling history into a cell's DNA. A CRISPR base editor, a tool that changes single DNA letters, is switched on in proportion to the signal. It then mutates engineered target sites, creating a heritable record. Imaging later reads this record together with each cell's gene expression, while keeping the cells in place. With this tool, the lab showed that cells remember their past response to BMP signaling for up to 18 days.
Why it matters
Knowing how signaling history guides cell decisions could inform tissue-engineering strategies for growing tissues with the right cell types and layout. It could also help explain, and eventually treat, diseases driven by faulty BMP, Wnt or related signaling. The recording tool itself may let researchers track signal histories in living mammalian systems.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Christopher Michael Sturgeon
Icahn School of Medicine at Mount Sinai, NY·Biology
Define the signaling, transcriptional and epigenetic mechanisms that specify each hemogenic mesoderm subset and restrict it to one blood program, aiming to improve in vitro production of progenitors including hematopoietic stem cells.
Qinglan Ling
University of Massachusetts Chan Medical School, MA·Genetics·Early-career
Develop and optimize a mitochondria-targeting base editor, a tool that changes single DNA letters, to create a truncating mutation in the mouse MTATP6 gene and generate a conditional mouse model.
Upasna Sharma
University of California-Santa Cruz, CA·Biology
Determine whether Mettl7a1, a predicted RNA methyltransferase that adds methyl tags to RNA, is needed for minor zygotic genome activation and normal early development in mouse preimplantation embryos.
The school
University of California-Los Angeles: 84 labs on PI Pages, $1.9B a year on research, 803 research doctorates a year.
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