About The Gupta Lab

Our lab investigates the cellular and molecular changes in chronic nerve compression (CNC) injuries, such as carpal tunnel syndrome, cubital tunnel syndrome, and spinal nerve root stenosis. These localized, peripheral neuropathies produce pain, altered sensation, and motor atrophy in millions of Americans each year. However, knowledge about the cascade of cellular and molecular events leading to injury is limited, as are the number of effective treatments for CNC patients.

In addition, we investigate methods of improving outcomes after spinal cord injuries. Spinal cord injuries often result in paralysis or disrupted motor and sensory function, and are accompanied by altered sensations and pain perception. Exploration of therapeutic treatments at the molecular level is of utmost importance to helping patients regain daily function and quality of life.

These twin areas of focus allow the PNRL to occupy a unique, cutting-edge position at the intersection of orthopaedics and neuroscience.Pathophysiology of CNC injury

The results of our previous work suggest that axonal pathology is not present during the early phases of CNC injury. We have since focused on elucidating the effects that CNC injuries have on Schwann cells and macrophages, at both gross ultrastructural and molecular levels, and in terms of electrophysiology. Our lab's research has shown CNC injuries to be associated with significant changes in expression of growth factors and other proteins necessary for proper myelination. In particular, Schwann cells switch from a promyelinating to a proliferative, nonmyelinating phenotype in response to mechanical stimulation. We are currently exploring whether this switch can be attributed to the mechanosensitive properties of Schwann cells, and whether the Schwann cells are able to respond directly to mechanical stimulation via integrin proteins.

Our results taken together suggest that CNC injuries differ significantly from acute nerve injuries, and have a fundamentally distinct pathogenesis compared to Wallerian degeneration. We are currently developing novel methods of studying CNC injury, which include an in-vivo mouse model as well as an in-vitro cell culture compression chamber. The in-vitro compression chamber model has the added advantage of allowing greater control of parameters such as ischemia and immune response to study the effect of mechanical stimulus on myelinated Schwann cells in culture. Using this information, we hope to utilize the in-vivo mouse model to explore potential molecular-based therapeutic treatments for CNC injuries.

Treatment of spinal cord injuries

In addition to examining the pathophysiology of peripheral neuropathies, we are also expanding on our research to examine potential treatments of spinal cord injuries. Our research on CNC injuries indicated that Schwann cells appear to demyelinate and then proliferate, which suggests they are switching to a pro-regenerative phenotype. Based on this observation, we transplanted sciatic nerve that had been preconditioned with mechanical stimulation into spinal cord hemisection injuries. This transplantation resulted in improved functional outcomes accompanied by regeneration.

Most recently, we have initiated studies on whether durotomies and duroplasties following spinal cord injury can similarly result in improved outcomes. Following spinal cord injury, pressure builds up in the spinal cord. It is beleived that this pressure can adversely effect the regenerative capacity of the cord.

 

 

For the second time in three years, the Orthopaedic Research & Education Foundation (OREF) has chosen one of UC Irvine Orthopaedic residents to receive their prestigious OREF Resident Clinician Scientist Training Grant. The 2014 recipient of this award is Dr. Minal Tapadia.

 

Dr. Ranjan Gupta has been selected as an ABC Traveling Fellow, one of the most prestigious orthopaedic awards and honors.

 

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