Lab Members

Collaborator:
Dr. Megan Detloff

Graduate students:
Kaitlin Ferrell, MD/PhD program

Research assistants:
Theresa Connors

Dr. Houle has a longstanding interest in spinal cord injury and the potential to promote structural and functional repair in acute and chronic injury situations. It is important to understand that a spinal cord injury is an evolving condition where for weeks to months after injury there continues to be change/modulation of the cellular and molecular components affected directly or indirectly by the injury. These changes often are most prominent at the site of injury but it is critical that we also understand how cells/tissues remote to the injury are affected. An example would be the effect of spinal cord injury on neurons in the brain that normally transfer information through axon pathways that have been damaged. The response to injury by neurons in the brain may include cell atrophy, cell death, change in gene expression, retraction of the damaged axonal process or an attempt to regrow the damaged axonal process.

Research in the laboratory is designed to examine multiple aspects of the neuronal and glial cell response to spinal cord injury with the intent of designing a combinatorial treatment strategy for regeneration leading to functional recovery. To accomplish this difficult task, the lab uses a variety of approaches, including:

1. Neurotransplantation to provide a substratum that will support the regrowth of injured axons and which may provide a source of precursor cells to form new neurons and glial cells, replacing those lost after spinal cord injury;
2. Treatment with neurotrophic and/or growth factors to provide essential molecules for cell survival and for initiating and maintaining axonal growth;
3. Modulation of glial scar tissue and associated extracellular matrix to reduce the negative features of what has been characterized as a structural and chemical barrier to axonal growth;
4. Exercise of injured limbs in the attempt to maintain joint fluidity and muscle strength and to re-train regions of the spinal cord that have been separated from descending input from the brain. There is strong evidence of activity-dependent plasticity within the brain and spinal cord after exercise, and we are especially interested in applying physical therapy and rehabilitation medicine techniques to determine if enhanced spinal cord plasticity will translate into greater behavioral recovery. As more information is gathered and placed into the puzzle, our understanding of the sequence of steps to be followed to promote recovery of function will become clearer.

Research techniques used in the laboratory range from gross anatomical examination to quantifying gene expression of single neurons. A typical experiment will include animal surgery, transplantation, physical therapy, a battery of behavioral analyses, preparation of tissue samples for light microscopy and immunocytochemical detection of specific cell types or tissue components, isolation of specific cells by laser micro dissection for extraction of RNA for analysis of gene expression by quantitative PCR, isolation of proteins for analysis of cell signaling by Western Blot or multiplex arrays.

Dr. Houle has received funding as the principal investigator (PI) from the NIH (both RO1 and PO1 grants), Paralyzed Veteran’s of America (Craig H. Neilsen Foundation), The Daniel Heumann Spinal Cord Fund, and the New York State Spinal Cord Injury Research Program. His primary NIH grant has been funded continually since 1988. In 2004, Dr. Houle was awarded a Jacob Javits Investigator Award for a distinguished record in neurological science research. He is the PI of the current NIH program project entitled "Spinal Cord Injury, Plasticity and Transplant-Mediated Repair."

Dr. Houle has authored 95 peer-reviewed publications and has served as an ad hoc and regular member for several NIH study sections, the National Science Foundation, the Christopher Reeve Foundation, Department of Veteran’s Affairs, Department of Defense and the New Jersey Commission on Spinal Cord Research. He served for six years on the scientific review panel for the Kentucky Spinal Cord and Head Injury Research Trust and currently is on the scientific review board for Mission Connect (associated with Texas Institute for Rehabilitation and Research).

"Third Annual Medical Student Research Day"
College of Medicine Newsroom (March 21, 2014)

Recent Selected Publications

“MicroRNAs 21 and 199a-3p Regulate Axon Growth Potential through Modulation of Pten and mTor mRNAs”
Kar AN, Lee SJ, Sahoo PK, Thames E, Yoo S, Houle JD, Twiss JL
eNeuro. 2021 Aug 11;8(4):ENEURO.0155-21.2021

“Exercise as a therapeutic intervention for neuropathic pain after spinal cord injury”
Houle, JD and Detloff MR
in Spinal Cord Injury Pain, Sang, CN and Hulsebosch, CE, eds. Academic Press, Elsevier Inc. 2021

“Altered intrinsic membrane properties of dorsal raphe serotonergic and GABAergic neurons following SCI may contribute to depressive behavior”
Farrell, KF and Houle JD
eNeuro (in press), 2020

“Plastic Changes after Spinal Cord Injury”
Farrell K, Detloff MR, Houle JD
Oxford Research Encyclopedia of Neuroscience, DOI:10.1093/acrefore/9780190264086.013.241, 2019

“Systemic inhibition of soluble TNF with Xpro1595 exacerbates a post-spinal cord injury depressive phenotype in female rats”
Farrell K and Houle JD
J Neurotrauma 36: 2964-2976, 2019

“Exercise-Induced Changes to the Macrophage Response in the Dorsal Root Ganglia Prevent Neuropathic Pain after Spinal Cord Injury”
Chhaya SJ, Quiros-Molina D, Tamashiro-Orrego AD, Houle JD, Detloff MR
J Neurotrauma 36:877-890, 2019

“Exercise and peripheral nerve grafts as a strategy to promote regeneration after acute or chronic spinal cord injury”
Theisen CC, Sachdeva R, Austin S, Kulich D, Kranz V, Houle JD
J. Neurotrauma, 34(10):1909-1914, 2017

"Intra-axonal protein synthesis - a new target for neural repair?"
Twiss JL, Kalinski AL, Sachdeva R, Houle JD
Neural Regeneration Res. 11(9):1365-1367, 2016

"Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury"
Hou S, Carson DM, Wu D, Klaw MC, Houlé JD, Tom VJ
Exp Neurol. 285:136-146, 2016

“Dynamic changes in local protein synthetic machinery in regenerating central nervous system axons after spinal cord injury”
Sachdeva R, Farrell K, McMullen M-K, Twiss JL, Houle JD
Neural Plasticity Vol 2016 Article ID Number 4087254, 2016

"Delayed exercise is ineffective at reversing aberrant nociceptive afferent plasticity or neuropathic pain after spinal cord injury"
Detloff MR, Quiros-Molina D, Javia AS, Duggubati L, Nehlsen AD, Ninan V, Vannix KN, McMullen MK, Amin S, Ganzer PD, Houle JD
Neurorehab. and Neural Repair 30(7): 685-700, 2016

"Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes"
Sachdeva R, Theisen CC, Ninan V, Twiss JL, Houle JD
Exp. Neurol. 276: 72-82, 2016

"mRNAs and Protein Synthetic Machinery Localize into Regenerating Spinal Cord Axons When They Are Provided a Substrate That Supports Growth"
Kalinski AL, Sachdeva R, Gomes C, Lee SJ, Shah Z, Houle JD, Twiss JL
J Neurosci. 35(28):10357-70, 2015

"Large animal and primate models of spinal cord injury for the testing of novel therapies"
Kwon BK, Streijger F, Hill CE, Anderson AJ, Bacon M, Beattie MS, Blesch A, Bradbury EJ, Brown A, Bresnahan JC, Case CC, Colburn RW, David S, Fawcett JW, Ferguson AR, Fischer I, Floyd CL, Gensel JC, Houle JD, Jakeman LB, Jeffery ND, Jones LA, Kleitman N, Kocsis J, Lu P, Magnuson DS, Marsala M, Moore SW, Mothe AJ, Oudega M, Plant GW, Rabchevsky AS, Schwab JM, Silver J, Steward O, Xu XM, Guest JD, Tetzlaff
Exp Neurol. 269:154-68, 2015

"Exercise after spinal cord injury as an agent for neuroprotection, regeneration and rehabilitation"
Sandrow-Feinberg HR, Houlé JD
Brain Res. 1619:12-21, 2015

"Either Brain-Derived Neurotrophic Factor or Neurotrophin-3 Only Neurotrophin-Producing Grafts Promote Locomotor Recovery in Untrained Spinalized Cats"
Ollivier-Lanvin K, Fischer I, Tom V, Houlé JD, Lemay MA
Neurorehab Neural Repair. 29: 90-100, 2015

“Peripheral nerve graft mediated axonal regeneration”
Tom, VJ, Houle JD
Neural Regeneration, So, KF, Xu, XM, eds. The Science Press, 2014

“MicroRNA Regulation of mTOR Activity”
Zambrotta, M, Houle, JD
miRNA in Regenerative Medicine, (Ed) CK Sen, Elsevier Press, 2014

“Exercise modulates chloride homeostasis after spinal cord injury”
Côté MP, Gandhi S, Zambrotta M, Houlé JD
J Neurosci. 2014 34(27):8976-87, 2014

“Acute exercise prevents the development of neuropathic pain and the sprouting of non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury”
Detloff MR, Smith EJ, Quiros Molina D, Ganzer PD, Houlé JD
Exp Neurol. 255:38-48, 2014