Project 1: Therapeutic potential of exercise hormone irisin/FNDC5 in neurodegenerative diseases such as Alzheimer’s disease using cross functional gene therapy, biomolecular, imaging, and behavioral approach.• Rescued cognitive, neuroinflammatory and neuropathology phenotype in neurodegenerative mouse models using AAV gene therapy peripherally (IV) or centrally (stereotaxic) by overexpressing target gene.• Demonstrated glia activation as a major contributor in our neurodegeneration models both in vitro (primary neuron, mixed glia and differentiated neuron from neuronal stem cell culture) and in vivo.• Reported significant astrocyte- and microglia-specific genes downregulation in irisin-treated AD mice with RNAseq data analysis.• Demonstrated transcriptome of adult-born neurons in the hippocampus is altered in global F5KO transgenic mice. • Confirmed cognitive decline in irisin/FNDC5 KO and neurodegenerative mouse models of aging, APP/PS1 Alzheimer’s mouse model using comprehensive cognitive behavior test battery including Morris water maze, Contextual Fear Conditioning and Novel Object Recognition test.• Optimized and validated bioanalytical methods to confirm target protein overexpression in brain tissue and plasma.Project 2: NRG1-ErbB3 signaling in brain microvascular endothelial cells and in traumatic brain injury models.• Demonstrated neuregulin-1/ErbB3 signaling is intricately connected with the cytoskeletal processes of the brain endothelium and contributes to morphological and angiogenic changes as well as to BBB integrity.• Evaluated how soluble vascular endothelial cadherin amplifies neuro-inflammation through interactions with microglia.Project 3: Effect of exercise on brain microstructure using advanced in vivo imaging DTI-MRI.Project 4: Effect of exercise hormone irisin/FNDC5 in stroke outcome.

>Identified the therapeutic window of investigational products by analyzing the toxicological properties.

>Investigated opioid agonists for their neuroprotective potential using in vitro and in vivo stroke models>Evaluated the pharmacodynamic (PD) effects and toxicological studies of selected lead compounds in middle cerebral artery occlusion (MCAO) preclinical stroke model.>Developed co-culture based blood brain barrier model to screen CNS drug in vitro.