Development of Advanced Therapeutic Strategies for Traumatic Brain injury: My research interests revolve around developing advanced therapeutic strategies for traumatic brain injury (TBI). TBI is a major public health and socioeconomic problem that affects both civilians and military personnel. However, despite being a major cause of mortality and morbidity there has been limited success in the development of effective treatments for TBI. Developing relevant therapeutic interventions for TBI has proven to be challenging, particularly due to the insidious, neurodegenerative course of the disease. Primary injury (mechanical damage to neuronal, glial, and vascular tissues caused by kinetic energy transfer) in TBI results in cell death and is not amenable to intervention. Secondary injury begins within a few hours after the initial mechanical insult and progresses by subsequent pathophysiological sequelae resulting in further neuronal damage. My research is focused on the development of therapeutic strategies that would simultaneously attenuate the secondary injury and begin to restore neuronal function in the brain after injury. Use of Extracellular Vesicles as a Therapeutic Tool in CNS Disorders and Trauma: Another major focus of my research is the use of extracellular vesicles (EVs) as a therapeutic tool in CNS disorders and trauma. EVs carry proteins and genetic material that can profoundly modify cellular function and may possess regenerative capabilities. Use of stem cell derived-EVs presents distinct advantages over the use of whole stem cells, as they may be less likely to produce a pulmonary first pass effect. Similarly, the possibility to replace stem cells with EVs would overcome the problem of graft rejection, which is always a hurdle in diseases with strong immunological components. We have standardized an isolation method to obtain current Good Manufacturing Practice (cGMP) compliant EVs from stem cells. We are further investigating the molecular mechanisms by which EVs modulate cellular function and exploring the therapeutic potential of EVs. Circulating Extracellular Vesicles as Biomarkers in Traumatic Brain Injury: In cases of injury, EVs released by cells can exhibit an array of proteins and nucleic acids linked to the pathophysiologic events and may be used as biomarkers to predict degree of cellular damage or provide accurate prognosis. Micro RNAs (miRNAs) constitute a major regulatory gene family and are involved in most biological processes. Temporal changes in EV-miRNA profiles have been demonstrated to accurately predict disease recurrence and overall patient survival in disease, including cancer. We aim to determine the miRNA expression profiles of EVs in circulating blood of TBI patients and examine the possible relationship between disease severity and miRNA expression changes. Analysis of EVs would provide unique "miRNA fingerprints" that will be helpful in TBI classification and treatment.
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