Aditya Raghunandan
University of Michigan-Dearborn, MI·Biomedical Engineering
The brain has to dispose of its own waste proteins, and when it fails, those proteins pile up in diseases including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). Cerebrospinal fluid — the clear fluid cushioning the brain — appears to flush these wastes out through channels that run alongside blood vessels.
- Fields
Biomedical Engineering
Engineering
Neuroscience
- Topics
cerebrospinal fluid
perivascular flow
glymphatic clearance
- Grants
- 1 known grant, through Apr 2028
What they work on
- Build a microphysiological system on a validated silicon-nitride membrane tissue-chip platform with independent dual-chamber flow control, to recreate perivascular flow from healthy steady conditions to the high pulsatility of aging and hypertension.
- Quantify aggregation kinetics of Amyloid-β-40 under steady and pulsatile flow using fluorescence assays and kinetic modeling, extracting nucleation, elongation, and fibril fragmentation rate constants.
- Correlate measured protein aggregation rates with hydraulic power dissipation in the device, to capture how much flow energy is available to drive protein misfolding.
- Test whether pathological pulsatile flow drives human brain vascular smooth muscle and endothelial cells, co-cultured in the chip, from a contractile phenotype to a pro-inflammatory state with reduced waste clearance, by identifying the mechanotransduction pathways activated.
More about the research
A puzzle motivates this project: waste builds up around arteries, where the fluid pulses with each heartbeat, but not around veins, where flow is steady. That is backwards from what one would expect, since clean fluid enters near arteries and waste-laden fluid leaves near veins. The proposal is that pulsatile flow itself, which grows stronger with age and disease, is the culprit.
Why it matters
Treatments for Alzheimer's and related diseases have overwhelmingly targeted biochemistry. If pulsatile cerebrospinal fluid flow actively drives protein clumping and damages the cells lining perivascular channels, then restoring healthy brain fluid dynamics becomes a therapeutic target in its own right, and flow measurements could serve as markers of waste-clearance failure in aging and hypertension.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Yunjie Tong
Purdue University, IN·Neuroscience
Measure how strongly changes in cerebral blood volume, the amount of blood in the brain, are coupled to cerebrospinal fluid (CSF) movement during both wake and sleep states.
Tracy A. Butler
Weill Medical College of Cornell University, NY·Neuroscience
Confirm, using additional complementary measurement methods, the preliminary finding that traumatic brain injury reduces brain cerebrospinal and interstitial fluid clearance, including the glymphatic pathway, in patients imaged within 14 days of injury.
Jonathan Kipnis
Washington University in St Louis, MO·Neuroscience
Determine whether failing meningeal lymphatic vessels speed up the aging of nearby meningeal blood vessels, using imaging, surgical and drug-based methods in aged mice and AD mouse models.
The school
University of Michigan-Dearborn: 3 labs on PI Pages, $12M a year on research, 20 research doctorates a year.
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