Miranda Orr
Washington University in St Louis, MO·Neuroscience
As we age, some cells stop dividing but do not die. These are called senescent cells, and in many tissues they release inflammatory signals that can harm the cells around them.
- Fields
Neuroscience
Medicine & Clinical Research
Computer Science
- Topics
cellular senescence
senescent neurons
Alzheimer's disease
- Grants
- 1 known grant, through May 2027
What they work on
- Identify general molecular markers of senescent neurons and how their microenvironment differs from that of healthy neurons, using spatial omics data from human ADRD brains and mouse models.
- Determine how senescent neurons contribute to neuron death in brain aging and ADRD, building on the finding that Fas receptor (CD95), a protein that triggers cell death, is overproduced near senescent neurons.
- Use deep learning models to simulate turning a single gene up or down in senescent neurons and predict how that change affects other genes in the surrounding tissue.
- Rank possible treatments that could reduce the harmful effects of senescent neurons using computational models, then test their mechanisms in mouse models of ADRD.
More about the research
This raises a question for Alzheimer's disease and related dementias (ADRD): do neurons that become senescent damage their neighbors, and could that damage be blocked? Answering it requires spatial omics. These are methods that measure hundreds of genes while keeping track of where each cell sits in the tissue. That makes it possible to see how one cell affects the area around it, called its microenvironment.
Why it matters
Alzheimer's disease and related dementias affect millions of older adults and have few effective treatments. If senescent neurons harm the brain cells around them, blocking that harm could offer a new way to slow brain aging. By finding molecular regulators and candidate treatments and testing them in mice, this work could point to new therapies for patients with dementia.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Toren Finkel
University of Pittsburgh, PA·Biology
Build a high-resolution map of senescent cells, cells that stop dividing permanently, in human lung and heart, using single-cell RNA and ATAC sequencing, proteomics and spatial transcriptomics.
Robert Krueger
New York University, NY·Computer Science·Early-career
Design scalable algorithms that jointly represent tissue images and omics data from spatial profiling, so that very large multimodal datasets can be explored interactively.
Balaji Krishnan
University of Texas Medical Branch at Galveston, TX·Neuroscience
Test how elevated levels and signaling of phospholipase D1 (PLD1), a lipid-cleaving enzyme, at synapses contribute to synaptic dysfunction and memory deficits in Alzheimer's disease and related dementias.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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