The research activities of the laboratory are focused in three principal areas:
At least 1.4 million people in the US sustain TBI annually, of these a large proportion are disabled and suffer lasting effects. Currently, there is no effective treatment for TBI. Several epidemiological studies have demonstrated that traumatic brain injury (TBI) is an epigenetic risk factor for the development of Alzheimer's disease. There is evidence to believe that abeta, a cytotoxic peptide that is thought to be involved in the pathogenesis of Alzheimer's disease, may participate in the neurodegenerative process that occurs after TBI.
The laboratory is investigating the role that abeta play in the functional recovery after TBI, utilizing transgenic tools to dissect the abeta neurodegenerative cascade in TBI, leading to potentially effective targeted treatment. This research is conducted in collaboration with Dr. Dale Bredesen of Buck Institute for Aging and Dr. Eddie Koo of UCSD.
Spinal cord injury (SCI) is an often permanent and devastating neurologic injury occurring in the prime of a patient's life, with one of the highest cost to society of all neurological disorders. Currently, aside from surgical decompression and stabilization of the spine, no effective disease modifying treatment for spinal cord injury exists. Therefore, novel approaches to the understanding of the pathophysiology and treatment of SCI are essential. Spinal cord injury initially results in edema at the site of injury due to disruption in the blood-spinal cord barrier and subsequently along the spinal cord within 48 hours after trauma. Aquaporin-4 (AQP-4) is a water channel expressed in the astrocytic foot-processes in the central nervous system and plays a role in the water hemostasis. The laboratory is investigating the role of AQP-4 in spinal cord injury, utilizing transgenic tools, behavioral assays, and advanced imaging techniques. This work is conducted in collaboration with Dr. Alan Verkman of UCSF.
In addition to understanding the molecular events surrounding SCI, laboratory efforts are focused on cell-based therapies. Adult stem cells are engineered and implanted into animals after SCI and motor functions are assessed. In collaboration with Dr. Reggie Edgerton in the Department of Integrative Biology and Physiology, research is being conducted on enhancing native spinal circuitry for locomotion in humans. This serves as a bridge therapy until effective regenerative treatments are available.
Intervertebral disc degeneration, one of the main causes of low back pain, is an irreversible process for which there are no restorative treatments. Histologically, the degeneration is characterized by a decrease in the water content, reduced proteoglycan levels, destruction of the annular structure, and flattening of the disc.
Current focus of the laboratory is on enhancing the regenerative capacity of the nucleus pulposus through the use of stem cells and/or growth factors. Stem cells are undifferentiated cells capable of long-term self-renewal and differentiation into specialized cells. Mesenchymal stem cells, which gives rise to the nucleus pulposus of the intervertebral discs can be easily obtained from a number of autologous sources (bone marrow, adipose tissue, muscle, and dermis). The laboratory is investigating methods of engineering these stems cells in a rodent model to become disc chondrocytes that could be incorporated into the degenerated disc, thereby reversing the degenerative process and restoring disc function.
A major component of the pathogenesis of disc degeneration involves decrease in the synthesis of proteoglycans by the intervertebral chondrocytes. Certain members of transforming growth factor-beta (TGF- beta) family of proteins are cytokines involved in chondrogenesis and have anabolic effects on disc chondrovytes. The laboratory is currently investigating methods of promoting proteoglycan synthesis in a rodent model by local delivery of growth factors into degenerated fragments.
In collaboration with the biomechanic laboratory of Dr. Denis D. DiAngelo at University of Tennessee, Memphis, these regenerated discs are subjected to functional biomechanical testing by a robot and comparisons are made to degenerated and normal discs.