Ashok Shetty
Texas A&M University-College Station, TX·Neuroscience
Brain injury and normal aging both leave behind long-lasting inflammation in the brain, along with trouble in memory, thinking and mood. Work here tests a cell-free alternative to stem cell transplants: tiny membrane bubbles called extracellular vesicles (EVs) that cells naturally release, packed with small regulatory RNAs (miRNAs) and proteins that can change how recipient cells behave.
- Fields
Neuroscience
Biomedical Engineering
Medicine & Clinical Research
- Topics
extracellular vesicles
exosomes
intranasal delivery
- Grants
- 2 known grants, through Jun 2030
What they work on
- Test whether nasal delivery of extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells in early or late middle age preserves memory and cognition into old age in mice.
- Determine whether the same vesicles given in old age reverse existing cognitive and memory deficits, measuring inflammation, AMPK activation, mTOR inhibition, autophagy, new neuron formation and synapse loss in hippocampus and medial prefrontal cortex.
- Ask whether microglia, the brain's resident immune cells, are required for vesicle benefits by depleting them at the time of treatment in middle-aged and aged mice.
- Test whether nasal mesenchymal stem cell vesicles given 4 or 24 hours after traumatic brain injury keep acute neuroinflammation from becoming chronic and preserve cognitive and mood function.
- Test whether the same vesicles help one month after injury, when inflammation and deficits are already chronic, tracking microglia and astrocyte states by single-cell RNA sequencing.
- Determine whether knocking down or deliberately loading specific anti-inflammatory miRNAs (miR-30e-3p, let-7c-5p, miR-20b-5p, miR-24-3p) changes the vesicles' therapeutic potency in chronic traumatic brain injury.
More about the research
Both projects deliver these vesicles through the nose, a non-invasive route that lets them reach the brain, and ask whether they can calm inflammation and restore function in aged brains and after traumatic brain injury.
Why it matters
There are no effective treatments for the lasting cognitive and mood problems after traumatic brain injury, and no therapy that reliably prevents age-related memory loss. Because these vesicles can be made from donor stem cell lines and given through the nose, they could become an off-the-shelf, needle-free treatment. If the mouse results hold, the work could inform trials for TBI patients in both early and chronic stages and for age-related dementia.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sarah Elzinga
Michigan State University, MI·Neuroscience·Early-career
Establish how the cGAS/STING pathway, a DNA-sensing innate immune alarm, and the surrounding inflammatory environment change as obesity and prediabetes progress from midlife to later life, and how this tracks with cognitive impairment.
Subhash Chand
University of Nebraska Medical Center, NE·Pharmacology
Test whether cannabidiol (CBD) reduces NLRP3 inflammasome activation, a key inflammation switch, in human monocyte-derived microglia exposed to HIV and methamphetamine, measuring gene expression from RNA and protein.
Wanling Xuan
University of South Florida, FL·Physiology
Test whether muscle progenitor cells made from human iPSCs with givinostat, a histone deacetylase–blocking drug, are effective and safe for regenerating aged muscle in an animal model of sarcopenia.
The school
Texas A&M University-College Station: 23 labs on PI Pages, $1.4B a year on research, 768 research doctorates a year.
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