BLR&D Research Career Scientist Application

Neurodegenerative disorders, a group of neurological illnesses, are currently affecting many veterans and non-veterans throughout the world. Among neurodegenerative disorders, while Alzheimer’s disease (AD) and Parkinson’s disease (PD) display progressive death of neurons in particular regions of the brain, diseases like multiple sclerosis (MS) and traumatic brain injury (TBI) exhibit demyelination and axonal weakness/dysfunction. Our lab primarily focuses on central nervous system (CNS) cell signaling that leads to neuronal death in PD and AD and demyelination in MS and TBI. All these disorders are characterized by activation of CNS glial cells (astroglia and microglia), unwarranted production of different proinflammatory molecules within the CNS, decrease in autophagy, and death of either oligodendroglia (MS and TBI) or neurons (AD and PD). Therefore, from several angles, we are investigating mechanisms by which glial cells are activated in the CNS to release different proinflammatory molecules and neurotoxins to cause neuroinflammation and neurodegeneration, leading to apoptosis and cell death of neurons and oligodendroglia. We are also involved in identifying intracellular signaling pathways by which lysosomal biogenesis and autophagy become dysfunctional in the CNS, resulting in protein aggregation or proteinopathy. Moreover, we will also engage in investigating mechanisms by which glial cells in the CNS may be redirected to produce neuroprotective molecules and neural stem cells could be driven towards neurons and myelin-producing cells (oligodendrocytes) within the neurodegenerative CNS. Finally, we are trying to suppress neurotoxic signaling pathways and/or boost neuroprotective signaling pathways in different animal models of neurodegenerative diseases by nontoxic drugs/monoclonal antibodies/small molecules/exercise and translate these interventions from the laboratory to neurology clinics in order to achieve neuroprotection in patients. Since many veterans are suffering from AD, PD, MS, and TBI, results from these studies will directly help veterans. 1