Riyi Shi, M.D., Ph.D.
Professor, Neuroscience and Biomedical Engineering, Department of Basic Medical Sciences
School of Veterinary Medicine
Weldon School of Biomedical Engineering
Center for Paralysis Research
M.D. Shanghai Jiaotong University, School of Medicine (1984)
Ph.D. Purdue University (1994)
The mechanisms of neuronal trauma and its recovery through restoration, repair, and regrowth.
This laboratory is interested in uncovering the mechanism of nerve injury and facilitating recovery. We are interested in various types of injury, including traditional mechanical injury, blast injury, as well as biochemical injuries to both the spinal cord and brain. Combining biological and engineering principles and technology, we have studied how tissue responds to external forces (deformation) by an objective (compression or stretch), or a pressure wave (blast injury). One of the many innovative technologies established in this laboratory is the double sucrose gap recording apparatus. This novel technology is superior in many ways to the previously established extracellular recording methods. These include but are not limited to, significantly higher signal to noise ratio, low requirements and higher efficiency of stimulus currents ensure minimal disturbance of signal recording, and minimal damage to the nerve tissue allows for long term (hours to a day) recording.
Another major effort in this lab is to devise effective interventions to facilitate recovery following neuronal trauma. Due to the different tissue characteristics during injury progression, we have established treatments for acute injury (mainly membrane damage), subacute injury (secondary injury such as oxidative stress), and chronic injury (regeneration and restoration). For the acute stage, we have pioneered the successful use of hydrophilic polymer polyethylene glycol (PEG) to rapidly reunite severed nerves, both structurally and functionally. In addition, PEG also seals membrane breaches in compressed and stretched nerves. For the subacute nerve injury, among other factors, we have identified an aldehyde product, acrolein, to be the key in oxidative stress that causes tissue damage. Anti-acrolein therapy has been shown to significantly enhance structural and functional recovery in SCI. Regarding regeneration, we have built an effective conduit that can mimic the basic tissue architecture that can greatly enhance neuronal regeneration. In addition to the strategies of repair and regrowth, we have also developed a method to restore function in axons that survived the trauma but are functionally silent. Demyelination causes functional deficits in axons, preventing conduction of electrical signals. However, we have found that potassium channel blockers, which act as artificial myelin, can overcome this deficit and enable damaged axons to reestablish their ability to conduct action potentials.
In summary, we employ a repertoire of diverse technologies to study neuronal pathology and effective interventions in neuronal trauma and degenerative diseases. This lab is truly a multidisciplinary laboratory by any modern standards. This is reflected by the fact that the techniques we use are complementary, yet vastly different. Furthermore, our student body also possesses diverse backgrounds. These are biology students, engineering students and dual-degree students, M.D./Ph.D and DVM /Ph.D Students. Therefore, this is a lab with an environment that can truly allow engineers and biologists to collaborate side by side and ultimately work as a single entity. This environment creates an outstanding training experience, which ultimately prepares the student for all future challenges and professional endeavors.
Li, M. and Shi, R. Stretch induced conduction deficits in Guinea Pig ex-vivo nerve J. Biomechanics. 40: 569-578. 2007.
Fu, Y., Wang, H., Shi, R., and Cheng. J. Noninvasive molecular imaging of intact myelin sheath by coherent anti-stokes raman scattering microscopy. American Biotechnology laboratory. 25: 12-13. 2007.
Liu-Snyder, P., Logan, M.P., Shi, R., Smith D.T., and Borgens, R. B. Neuroprotection from secondary injury by polyethylene glycol requires its intracellular presence. Journal Experimental Biology. 282: 13073-86. 2007
Fu, Y., Wang, H., Shi, R., and Cheng, J. Second Harmonic and Sum Frequency Generation Imaging of Fibrous Astroglial Filaments in ex vivo Spinal Tissues. Biophysical J. 92: 3251-9. 2007
Nehrt, A, Rodgers, R, Shapiro, S, Borgens, R, and Shi, R. The Critical role of voltage-dependent calcium channel in axonal repair following mechanical trauma. Neuroscience. 146: 1504-1512. 2007
Ninan, L., Stroshine, R.L., Wilker, J.J. and Shi, R. Adhesive strength and curing rate of marine mussel protein extracts on porcine small intestinal submucosa (SIS). Acta Biomaterialia. 3:687-694. 2007.
Luo, J., and Shi, R. Polyethylene glycol inhibits apoptotic cell death following traumatic spinal cord injury. Brain Research. 1155: 10-16. 2007.
Fu, Y., Wang, H., Huff, T, Shi, R., and Cheng, C. Coherent Anti-Stokes Raman Scattering Imaging of Myelin Degradation Reveals a Calcium Dependent Pathway in Lyso-PtdCho Induced Demyelination. J. Neurosci. Res. 85:2870-2881. 2007.
Galle, B., Ouyang, H., Shi, R., and Nauman, E. Correlation between tissue-level stress and strains and cellular damage within the guinea pig spinal cord white matter. J. Biomechanics. 40: 3029-3033. 2007.
McBride, J. M., Smith, D. T., Byrn, S. R., Borgens, R. B. and Shi, R. 4-Aminopyridine Derivatives Enhance Impulse Conductionin Guinea Pig Spinal Cord Following Traumatic Injury. Neuroscience. 148: 44-52. 2007.
Li, M. and Shi, R. Fabrication of Patterned Multi-walled Poly-L-Lactic Acid Conduits for Nerve Regeneration. Journal Neuroscience Method. 165: 257-264. 2007.
Hamann, K., Nehrt, G., Ouyang, H., Duerstock, D. and Shi, R. Hydralazine inhibits compression and acrolein-mediated injuries in ex vivo spinal cord. Journal of Neurochemistry. 104: 708-718. 2008.
Ouyang, H., Galle, B., Li, J., Nauman, E., and Shi, R. Biomechanics of spinal cord injury: a multimodal investigation using ex vivo guinea pig spinal cord white matter. Journal of Neurotrauma. 25: 19-29. 2008
Li, M., McNally, H. and Shi, R. Enhanced neurite alignment on micro-patterned poly-L-Lactic Acid films. Journal of Biomedical Materials Research: Part A. 87: 392-404. 2008.
Li, M, Rickett, T., and Shi R. Peripheral Nervous System Repair: Current Progress and Future Trends in Axonal Regeneration and Guidance (invited review). Progress in Neuroscience, 5. 2008
Cho, Y., Shi, R., Borgens, R., and Ivanisevic, A. The Functionalized Mesoporous Silica Nanoparticles (MSNs) Based Drug Delivery System to Rescue Acrolein-Mediated Cell Death. Nanomedicine. 3: 507-519. 2008
Cho, Y., Shi, R., Borgens, R and Ivanisevic, A. Repairing the damaged spinal cord and brain with nanomedicine. Small. 4: 1676-1681.2008.
Hamann, K., Durkes, A., Ouyang, H., Pond, A., and Shi, R. Critical Role of acrolein in secondary injury following ex vivo spinal cord trauma. J. Neurochemistry. 107: 712-721. 2008.
Sun, W., Smith, D., Bryn, S., Borgens, R, and Shi, R. N-(4-pyridyl) methyl carbamate inhibits fast potassium currents in guinea pig dorsal root ganglion cells. Journal of Neurological Sciences. 277: 114-118. 2009.
Ouyang, H., Galle, B., Li, J., Nauman, E., and Shi, R. Critical roles of decompression in functional recovery of ex vivo spinal cord white matter. Journal of Neurosurgery Spine. 10: 161-170. 2009.
Li, J., Rickett, T., and Shi, R. Biomimetic nerve scaffolds with aligned intraluminal microchannels: a sweet approach to tissue engineering. Langmuir. 25: 1813-1817. 2009
Chen, H., Quick, E., Leung, G., Hamann, K., Fu, Y., Cheng, J and Shi, R. Polyethylene Glycol protects injured neuronal mitochondria. Pathobiology . 76: 117-128, 2009.
Rickett, T., Li, M., Patel, M., Sun, W., Leung, G., and Shi, R. Ethyl-Cyanoacrylate is Acutely Non-Toxic and Provides Sufficient Bond Strength for Anastomosis of Peripheral Nerves. Journal of Biomedical Materials Research: Part A. 90:750-4. 2009
Cho, Y., Shi, R., Ivanisevic, A., and Borgens. A mesoporous silica nanosphere-based drug delivery system using electrically condcting polymer. Nanotechnology. (2009 Jun 16. Epub ahead of print)
Fu, Y., Sun, W., Shi, Y. Shi, R, and Cheng, J. "Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction." PLoS ONE, In press.
Sun, W., Smith, D., Fu, Y., Cheng, J., Bryn, S., Borgens, R. and Shi, R. "A novel potassium channel blocker, 4-AP-3-MeOH, inhibits fast potassium channels and restores axonal conduction in injured guinea pig spinal cord white matter." Journal of Neurophysiol. accepted.