Translational Neuroscience Research Program
Translational Neuroscience is basic and applied scientific research aim to apply our current understanding of neuroscience and neurological diseases with new knowledge that will realistically translate into measurable benefits and therapeutic intervention to individuals.
To identify novel and innovative approaches to diagnose and treat diseases of the nervous system.
Peripheral Neural Repair and Regeneration
Injuries to the nerves within the peripheral nervous system trigger regenerative responses and injured nerves do regenerate, albeit slowly. However, clinical experience demonstrates that outcomes in patients who sustain nerve injury, even after microsurgical repair, is often suboptimal. The primary objective of our laboratory is to understand this discrepancy in regenerative capacity as well as the return of function in patients.
Using our chronic nerve injury model that accurately mimics chronic nerve injuries in human, we found that the delayed regeneration of the injured nerve results in the loss of growth-supportive Schwann cell (i.e., chronic Schwann cell denervation) and decline in the regenerative capacity of the injured neurons (i.e., chronic neuronal axotomy). These 2 effects result in poor axonal regeneration and subsequent suboptimal return of function. However, the exact mechanisms of why injured Schwann cells lose their robust capacity to support regeneration are not yet fully understood. Hence, our laboratory focuses on further elucidation of the underlying mechanisms of the onset of chronic Schwann cell denervation and on developing and refine experimental (potentially clinically applicable) strategies to reverse the effects of chronic Schwann cell denervation and chronic neuronal axotomy on axonal regeneration.
- Our lab demonstrated that the cytokine TGF-beta, when applied locally to the injured nerve, either alone or in combination with other neurotrophic agents, such as FK506 and forskolin, promoted nerve outgrowth and reverse the deleterious effect of chronic axotomy
- We are evaluating the efficacy of brief (1 hr) application of functional electrical stimulation to promote axonal regeneration when applied after immediate or delayed nerve repair.
- We are exploring the use of adult adipose-derived stem cells that have the potential to become Schwann- like cells to promote and support axonal regeneration.
Stroke and Intracerebral Hemorrhage
Intracerebral hemorrhage (ICH) accounts for 15-20% of all patients with ‘stroke’ and carries a significant morbidity and mortality of greater than 60%. Following acute ICH, different pathological processes are activated– apoptosis and necrosis, blood brain barrier (BBB) damage, cerebral edema and inflammation. Hematoma expansion and cerebral edema are usually associated with poor outcomes after ICH. The varying predominance of one or more of these biological processes will likely influence subsequent clinical outcomes. Since cellular activity facilitates these pathological processes, modulators of messenger RNA (mRNA) and protein involved in these processes are a likely target for therapeutic interventions and biomarkers discovery. MicroRNAs (miRNAs) are important regulators of mRNA and protein synthesis and have been implicated in different neurological diseases. Following tissue injury, miRNAs are released into the extracellular tissue space. There is mounting evidence to suggest that miRNAs circulating in plasma and serum are associated with specific disease processes. Cerebrospinal fluid (CSF) has also been an important surrogate for tissue samples in the diagnosis and management of brain and spinal cord disease. Our laboratory focuses on how miRNAs pattern in blood and cerebrospinal fluid can be used to diagnose stroke and its cause, in post-traumatic epilepsy, and to assess their expression patterns to clinical outcome.