Karunya Kandimalla
University of Minnesota, MN·Pharmacology
The brain depends on a dense network of tiny blood vessels that deliver fuel, hormones and oxygen and keep harmful substances out. The cells lining those vessels work together with the brain cells around them, and this partnership breaks down in Alzheimer's disease.
- Fields
Pharmacology
Neuroscience
Biomedical Engineering
- Topics
Alzheimer's disease
neurovascular unit
neurovascular coupling
- Grants
- 2 known grants, through May 2028
What they work on
- Build NUGENT, a deep-learning framework that infers cell-type composition and cell-type-specific gene expression from brain tissue data, to recover signatures of scarce endothelial cells and pericytes that standard deconvolution methods miss.
- Validate NUGENT against new single-cell RNA sequencing of neurovascular unit cells isolated from APPswe/PSEN1dE9 Alzheimer's model mice and their non-transgenic littermates.
- Apply NUGENT to mouse and public human datasets to map molecular pathways regulating neurovascular coupling, the coordinated activity of vessel and brain cells, in cognitively normal and Alzheimer's brains.
- Determine how type-2 diabetes conditions alter insulin trafficking and signaling at the blood-brain barrier, using dynamic SPECT/CT tracer imaging of insulin uptake kinetics and reverse phase protein arrays in mouse models.
- Test whether soluble amyloid beta peptides alone and together with diabetes conditions synergistically reduce insulin delivery to the brain across the cerebrovascular endothelium.
- Identify the insulin transcytosis pathways at the blood-brain barrier that are vulnerable to amyloid beta and impaired insulin signaling, using flow cytometry and TIRF microscopy in barrier cell monolayers.
More about the research
Two projects examine that breakdown from complementary directions: one builds computational tools to read out molecular changes in the rare cells of the brain's vessels, and the other measures how diabetes and Alzheimer's-related proteins block insulin from reaching the brain.
Why it matters
Both projects aim at the vascular side of Alzheimer's disease, which is poorly understood yet may drive age-related cognitive decline. Deep-learning readouts of rare vessel-wall cells could reveal new biomarkers and drug targets. Mapping how diabetes and amyloid beta choke off insulin delivery to the brain could support repurposing of drugs already approved for diabetes or stroke to treat brain insulin resistance in patients with Alzheimer's disease and type-2 diabetes.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Ethan Lippmann
Vanderbilt University, TN·Biomedical Engineering
Measure how dose affects gene and protein silencing by siRNA-EG18, an siRNA linked to an albumin-binding fatty acid carrier, in brain myeloid cells after injection into cerebrospinal fluid, targeting the Alzheimer's risk gene Cd33.
Dritan Agalliu
Columbia University, NY·Neuroscience
Test how glutamate levels regulate deep retinal vessel growth and blood-retina barrier integrity, using Vglut1 mutant mice (no glutamate release) and Gnat1 mutant mice (constant release), and how this interacts with acetylcholine-driven activity waves.
Jiebiao Wang
University of Pittsburgh, PA·Mathematics & Statistics
Improve estimation of cell-type fractions in bulk brain tissue by building an ensemble over existing deconvolution methods and incorporating the hierarchical relationships among brain cell types.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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