Understand and harness CNS plasticity to promote recovery of function after brain and spinal injury through bench-science and translational computational approaches.
Our research focuses on mechanisms of recovery after neurological trauma. Injuries to the brain and spinal cord invoke numerous, interacting biological changes that work in concert to determine recovery success. Some of these biological changes have contradictory effects at different phases of recovery. For example, mechanisms of synaptic regulation can contribute to cell death in the early phases of recovery but may promote plasticity and restoration of the function at later stages. Understanding the mechanisms of neurological recovery in the complex microenvironment of the injured central nervous system (CNS) requires large-scale integration of biological information and functional outcomes (i.e., Bioinformatics). Our work uses a combination of laboratory studies and statistical modeling approaches to provide an information-rich picture of the syndrome produced by trauma in translational in vivo models. The long-term goal of this research is to provide system-level therapeutic targets for enhancing recovery of function after brain and spinal injury.
AREAS OF FOCUS
Computational Syndromic Discovery: Development of an aggregate database of basic spinal cord injury research data from multiple research centers to enable sophisticated knowledge-discovery, data-sharing, and multivariate quantification of the complete constellation of changes produced by spinal cord injury.
Bench science: Modulation of glutamate receptor metaplasticity and its role in spinal cord learning and recovery of function after spinal cord injury. Techniques: biochemistry (quantitative western, qRT-PCR, ELISA), histology (immunohistochemistry, in situ hybridization), quantitative image analysis (robotic microscopy, confocal, deconvolution, image math) and behavioral analysis (locomotor scaling, fine-motor control, learning, and memory).
FUNDING AND CONTRIBUTORS
NIH, VA, DoD, Wings for Life Foundation, Craig H. Neilsen Foundation
CURRENT LAB MEMBERS
Jessica L Nielson, Ph.D., Assistant Professional Researcher
Vladimir Muraru, MS, Core Database Developer
Jenny Haefeli, Ph.D., Postdoctoral Scholar
Carla Arellano, B.S., DPT graduate student
Lauren Vancitters, B.S., DPT graduate student
FORMER LAB MEMBERS
Ellen D. Stuck, SRA II, current position: UCSF Doctorate of Physical Therapy Graduate Student
Aiwen Liu, B.S., SRA/bioengineer, current position: Medical Student at Virginia Tech
UCSF: Michael S. Beattie, Ph.D.; Jacqueline C. Bresnahan, PhD; Geoffery T. Manley, MD/PhD; Susanna Rosi, PhD; Mark Segal, PhD; Hua Su, MD; Esther L. Yuh, MD/PhD
UCSD: Mark H. Tuszynski, MD/PhD; Ephron S. Rosenzweig, PhD
UCLA: V. Reggie Edgerton, PhD
University of Louisville: Scott R. Whittemore, PhD; David S.K. Magnuson, PhD; Darlene Burke, MS
Texas A&M University: James W. Grau, PhD; Michelle A. Hook, PhD
The Ohio State University: Phillip G. Popovich, PhD; Dana M. McTigue, PhD; D. Michele Basso, EdD
Stanford University: Karen-Amanda Irvine, PhD
SELECTED PUBLICATIONS (selected from 137 papers and abstracts)
Ferguson, A.R., Irvine, K-A., Gensel, J.C., Nielson, J.L., Lin, A., Ly, J., Segal, M.R., Ratan, R.R., Bresnahan, J.C., Beattie, M.S. (2013). Derivation of multivariate syndromic outcome metrics for consistent testing across multiple models of cervical spinal cord injury in rats. PLoS One. e59712. doi: 10.1371/journal.pone.0059712
Kutcher, M.E., Ferguson, A.R., Cohen, M.J. (2013). A principal component analysis of coagulation after trauma. Journal of Trauma and Acute Care Surgery. 74(5):1223-9; discussion 1229-30. doi: 10.1097/TA.0b013e31828b7fa1
Yuh, E.L., Mukherjee, P., Lingsma, H.F., Yue, J.K., Ferguson, A.R., Gordon, W.A., Valadka, A.B., Schnyer, D.M., Okonkwo, D.O., Maas, A.I.R., Manley, G.T. (2013). MRI and CT Improve 3-month outcome prediction in mild TBI. Annals of Neurology, 73, 224-35 doi: 10.1002/ana.23783
Ferguson, A.R., Huie, J.R., Crown, E.D., Hook, M.A., Garraway, S.M., Lee, K.H., Hoy, K.C., Grau J.W. (2012). Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury. Frontiers in Physiology 3:399. doi: 10.3389/fphys.2012.00399
Huie, J.R.*, Baumbauer, K.M., Lee, K.H., Beattie, M.S., Bresnahan, J.C., Ferguson, A.R.*, Grau, J.W. (2012). Glial tumor necrosis factor alpha (TNFα) generates metaplastic inhibition of spinal learning. PLoS One.doi:10.1371/journal.pone.0039751 *co-corresponding author
Stück, E.D., Christensen, R.N., Huie, J.R., Tovar, C.A., Miller, B.A., Nout, Y.S., Bresnahan, J.C., Beattie, M.S., Ferguson, A.R. (2012). Tumor necrosis factor alpha (TNFα) mediates GABAA receptor trafficking to the plasma membrane of spinal cord neurons in vivo. Neural Plasticity.doi:10.1155/2012/261345
Nout, Y.S., Ferguson, A.R., Strand, S.C., Moseanko, R., Hawbecker, MS., Zdnowski, S, Nielson, J.L., Roy, R.R., Zhong, H., Rosenzweig, E.S., Brock, J.H., Courtine, G., Edgerton, V.R., Tuszynski, M.H., Beattie, M.S., Bresnahan, J.C. (2012). Methods for functional assessment after C7 spinal cord hemisection in the rhesus monkey. Neural Rehabilitation and Neural Repair. doi:10.1177/1545968311421934.
Rosenzweig, E.S., Courtine, G.C., Jindrich, D.L., Brock, J.H., Strand, S.S., Ferguson, A.R., Nout, Y.S., Roy, R.R., Miller, D., Beattie, M.S., Havton, L.A., Bresnahan, J.C., Edgerton, V.R., Tuszynski, M.H. (2010). Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nature Neuroscience, 13, 1505-1510.
Irvine, K-A., Ferguson, A.R., Mitchell, K.D., Beattie, S.B., Beattie, M.S., and Bresnahan, J.C. (2010). A novel method for assessing proximal and distal forelimb function in the rat: The Irvine, Beatties and Bresnahan (IBB) Forelimb Scale. Journal of Visualized Experiments.46, http://www.jove.com/Details.stp?ID=2246.
Ferguson, A.R., Christensen, R.N., Gensel, J.C., Miller, B.A., Sun, F., Beattie, E.C., Bresnahan, J.C., & Beattie, M.S. (2008). Cell death after spinal cord injury is exacerbated by rapid TNFα-induced trafficking of GluR2-lacking AMPARs to the plasma membrane. Journal of Neuroscience, 28,11391-11400.
Ferguson, A. R., Bolding, K.A., Huie, J. R., Hook, M. A., Santillano, D.R., Miranda, R.C. & Grau, J. W. (2008). Group I Metabotropic Glutamate Receptors Control Metaplasticity of Spinal Cord Learning through a PKC-Dependent Mechanism. Journal of Neuroscience, 28, 11939-11949.