Research Career Scientist for Naren Banik, PhD

Naren Banik 博士的研究职业科学家

• 批准号: 10476736
• 负责人: NAREN L BANIK
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10476736
• 关键词: Affect; Animal Diseases; Animal Model; Attenuated; Autoimmune Diseases; Axon; Biochemical; Biodistribution; Bladder; Bone Density; Brain; Calpain; Cell Death; Cells; Chemotaxis; Chronic; Clinical; Complex; Data; Degenerative Disorder; Disease; Disease Progression; Doctor of Philosophy; Dose; Drug Delivery Systems; Estrogens; Event; F-Box Proteins; Gel; Goals; Health; Immune; Impairment; In Vitro; Infiltration; Inflammation; Inflammation Mediators; Inflammatory; Injury; Investigation; Kinetics; Laboratories; Lesion; Life; Link; MPTP mouse; MPTP treatment; Medical; Methylprednisolone; Microglia; Modeling; Multiple Sclerosis; Muscle Fibers; Muscular Atrophy; Myelin; Myoblasts; Nerve Degeneration; Nervous System Trauma; Neurodegenerative Disorders; Neurologic Deficit; Neuronal Dysfunction; Neuronal Injury; Neurons; Neurophysiology - biologic function; Parkinson Disease; Pathway interactions; Plasma; Play; Process; Property; Protein Isoforms; Rattus; Recovery; Recovery of Function; Regulation; Research; Research Activity; Research Project Grants; Role; Safety; Sampling; Scientist; Site; Skeletal Muscle; South Carolina; Spinal Cord; Spinal Injuries; Spinal cord injury; Substantia nigra structure; T-Cell Activation; T-Lymphocyte; Techniques; Testing; Therapeutic; Tissues; Toxic effect; Tumor-infiltrating immune cells; Universities; Veterans; arm; attenuation; bone loss; calpain inhibitor; career; cell motility; cell type; chemokine; cytokine; disorder control; dopaminergic neuron; improved; improved functioning; in vivo; medication safety; motor impairment; multiple sclerosis patient; muscle RING finger 1; muscle degeneration; myelin degeneration; nanoparticle; neuroprotection; novel; novel strategies; novel therapeutics; preservation; programs; relating to nervous system; research clinical testing; skeletal muscle wasting; translational potential

Current research activities are focused on Spinal Cord Injury (SCI), Parkinson’s Disease (PD), and Multiple Sclerosis (MS). SCI is a complex debilitating condition leading to life-long neurological deficits as well as bone loss and muscle atrophy due to immobility. Our laboratory was among the first to show that estrogen (E2) drives neuroprotection in experimental SCI in rats, suggesting E2 warrants clinical evaluation in neurotrauma. New smart drug delivery techniques, including nanoparticles, may allow for increased drug safety and improved efficacy. Thus, the goal is to examine the effects of a novel slow release E2-loaded nanoparticle (SNP-E2) gel patch on neuronal dysfunction and skeletal muscle loss in a rat model of SCI. We hypothesize that focal delivery of estrogen via slow release nanoparticles SNP-E2 will maintain low systemic E2 levels (plasma) and higher tissue concentrations, thereby allowing for maximized therapeutic potential for recovery from neural and skeletal muscle loss in SCI. To test the hypothesis, two specific aims are proposed: (Aim 1) Examine the delivery of a novel slow release SNP-E2 and determine its kinetics, bio-distribution, toxicity, and effects in moderate and severe SCI and (Aim 2) Determine the effects of SNP-E2 on alterations of skeletal muscle loss in moderate and severe SCI. Overall, the proposed studies should provide a safe and novel strategy to improve health and functional recovery for Veterans with SCI. Parkinson’s disease (PD) is a progressive degenerative disorder affecting almost 80,000 Veterans. While the mechanisms of this degenerative process remain elusive, chronic inflammation may be involved. Calpain not only plays a pivotal role in brain (SN-DA neurons) and spinal cord (SC) degeneration, it may also drive inflammation and disease progression. Inhibition of calpain attenuates a distinct subpopulation of T cells in MPTP mice, suggesting calpain’s involvement in the inflammatory process. Our goal is to develop therapeutic strategies to treat PD with agents that block the inflammatory process, protect neurons, control disease progression, and improve function. We hypothesize that calpain activation, infiltration of inflammatory T cells (Th1/Th17), and released cytokines and chemokines are involved in progressive degeneration of PD, and calpain inhibitor treatment may reduce degeneration, slow disease progression, and improve function. Two specific aims will test the hypothesis: (Aim 1) Investigate the role of calpain regulation and T cell infiltration in SC degeneration and disease progression in MPTP mice, characterize infiltrating T cells, assess cytokine/chemokine levels in sera, and determine cell death parameters and calpain activation in SC; (Aim 2) Examine whether treatment of MPTP mice with calpain inhibitor will reduce degenerative inflammatory events and improve function. Increased calpain activity has also been found in MS as well as in its animal model [experimental autoimmune disease (EAE)], and calpain is implicated in the activation of T cells (Th1/Th17), degradation of axon/myelin, and T cell chemotaxis. While calpain is activated in brain and spinal cord of MS patients, the precise involvement of the two calpain isoforms, calpain-1 and calpain-2, remains undefined. We hypothesize that activation of distinct calpain isoform may favor expansion of inflammatory mediators and Th1/Th17 cells in MS patients, which could be attenuated by calpain inhibition. Studies include (Aim 1) testing MS patient samples to determine which of the two major calpain isoforms is involved in dysregulation of immune cell types, influencing immune arms of the disease; and (Aim 2) Investigating whether a distinct calpain isoform is linked with disease progression, influ- encing the neurodegenerative process in MS. Data obtained will reveal the effect of calpain inhibitor on inhibition of specific calpains and attenuation of both immune and neurodegenerative arms of the disease for developing novel therapy for treating MS and other neurodegenerative diseases. The overall goal of these research projects is to minimize degeneration and maximize function and improve the health of our Veterans.

目前的研究主要集中在脊髓损伤（SCI）、帕金森病（PD）和多发性硬化症