Jagdish Singh

What they work on

1. Synthesize liposomal nanoparticles and omega-3-fatty-acid-grafted chitosan nanomicelles carrying plasmid DNA for VGF, surface-modified with transferrin, mannose and cell-penetrating peptides, and characterize size, charge, uptake, transfection and toxicity.
2. Test whether VGF-loaded nanocarriers cross a human blood-brain barrier model built from brain endothelial cells and astrocytes, and lower secreted amyloid-β and tau phosphorylation in APP- or MAPT P301L-overexpressing SH-SY5Y cells.
3. Evaluate biocompatibility, organ toxicity, biodistribution and brain VGF expression after intravenous and intranasal dosing in wild-type mice at 3 and 24 months of age.
4. Assess whether VGF gene delivery improves behavior, synaptic function and amyloid pathology in 5xFAD amyloid-model mice, and in patient-derived iPSC neurons and cerebral organoids.
5. Build PEGylated liposomes containing chitosan–APOE2 plasmid polyplexes with transferrin and brain-specific cell-penetrating peptides such as RVG-9R, tetanus toxin C fragment and penetratin, and measure transport and effects on amyloid-β and tau in a human blood-brain barrier co-culture.
6. Determine whether APOE2 gene delivery reduces cognitive impairment, amyloid and tau pathology in APP/PS1 and PS19 mice and aged wild-type mice, using plasma neurofilament light chain and in vivo microdialysis of brain amyloid-β clearance.
7. Expand pancreatic cancer research infrastructure by mentoring junior investigators on drug delivery into dense tumors, new therapeutic agents and epigenetic-genetic changes in patient tissue, and by growing animal, patient-derived xenograft, biobank and biostatistics core facilities.

More about the research

Why it matters

Alzheimer's disease accounts for most dementia in the elderly and affects millions of Americans, with no treatment that halts it. Non-viral nanoparticles that deliver VGF or APOE2 genes across the blood-brain barrier, including through a needle-free nasal route, could become a therapeutic strategy for Alzheimer's and age-related cognitive decline. The pancreatic cancer center supports work on a cancer with roughly 11 percent five-year survival, including drug delivery into dense tumors and tissue-based markers that could guide treatment.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Closest labs

The school

North Dakota State University: 4 labs on PI Pages, $200M a year on research, 129 research doctorates a year.

More about North Dakota State University

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