Kathryn J. Jones, Ph.D.
Professor and Chair, Department of Anatomy and Cell Biology, IUSM
Research Career Scientist, Roudebush VA Hospital
Ph.D., University of Illinois at the Medical Center (1983)
Postdoctoral Fellowship, The Rockefeller University (1983-1986)
Neural Injury and Repair; Gonadal Steroids as Neurotherapeutics; Neuroimmunology and ALS.
The overarching goal of the research being conducted in our laboratory is to elucidate basic mechanisms underlying neural injury and repair in the mammalian nervous system following injury and/or disease. In vivo injury studies include both peripheral nerve injury (PNI) and spinal cord injury (SCI) animal models, immunodeficient animals, and an animal model of amyotrophic lateral sclerosis (ALS). In vitro studies include stem cell-derived motoneurons, and olfactory ensheathing cells as transplant material in SCI. Our long term goal is to translate our understanding of neural injury and repair to the clinical situation. There are currently 3 directions of research being conducted. First, we are investigating gonadal steroid hormones as neurotherapeutic agents in PNI and SCI. We are currently studying the combination of gonadal steroids and electrical stimulation in accelerating functional recovery after several different types of facial nerve damage, recurrent laryngeal crush injury, and sciatic nerve damage. These studies are being done in collaboration with clinical colleagues in Otolaryngology and Neurosurgery, and have the potential of translational application to clinical situations involving various types of peripheral nerve damage in humans. We are also examining the ability of gonadal steroid hormones to be neuroprotective after acute contusion spinal cord injury at the cervical level - a model relevant to our veteran population today. These studies are being done in collaboration with Dr. John Houle at Drexel University, and include combinatorial treatment strategies utilizing growth factors and olfactory ensheathing cells to promote axonal regeneration and behavioral recovery following neuroprotective treatment with gonadal steroid administration immediately after SCI. Second, we have discovered, in collaboration with Dr. Virginia Sanders at The Ohio State University, that CD4+ T cells can rescue motoneurons (MN) from injury-induced cell death and identified a physiologically relevant endogenous mechanism of immune-mediated neuroprotection. Recently, we have initiated work with an animal model of ALS, the SOD1 mouse, and found that the neuroprotective mechanism underlying immune-mediated rescue of MN after injury is defective in the SOD1 animal. Importantly, the defect may not be in the MN itself, but rather in a dysregulated microenvironment surrounding the MN cell body and/or a peripheral immune cell defect. These results are potentially paradigm-shifting in terms of our understanding of the underlying pathogenesis and progression of ALS, and are being done with clinical colleagues in Neurology. Finally, we are developing an in vitro PNI injury model utilizing stem cell-derived motoneurons and microfluidic chambers, and will explore peripheral immune cell-MN interactions from a tissue culture perspective with this system.
DeLucia, T.A., Alexander, T.D., Fargo, K.N. and Jones, K.J. (2008) Effects of single vs. combinatorial treatment strategies on beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons. Restor. Neurol. Neurosci., 25(5-6): 573-584.
Xin, J., Wainwright, D.A., Serpe, C.J., Sanders, V.M. and Jones, K.J. (2008) Phenotype of CD4(+) T cell subsets that develop following mouse facial nerve axotomy. Brain Behav. Immun., 22(4): 528-537.
Fargo, K.N., Alexander, T.D., Tanzer, L., Poletti, A. and Jones, K.J. (2008) Androgen regulates neuritin mRNA levels in an in vivo nerve regeneration model. J. Neurotrauma, 25: 561-566.
Hetzler, L.E.T., Sharma, N., Tanzer, L., Wurster, R.D., Leonetti, J.P., Marzo, S.J., Jones, K.J. and Foecking, E.M. (2008) Accelerating functional recovery after rat facial nerve injury: Effects of gonadal steroids and electrical stimulation. Otolaryngol. Head Neck Surg., 39: 62-67.
Lal, D., Hetzler, L.T., Sharma, N., Wurster, R.D., Marzo, S.J., Jones, K.J. and Foecking, E.M. (2008) Designing therapeutic strategies to accelerate functional recovery after rat facial nerve injury: Effects of electrical stimulation. Otolaryngol. Head Neck Surg., 39: 68-73.
White, F.A., Jones, K.J. (2008) IL-1? signaling initiates inflammatory hypernocicetion. Brain, Behav. Imm., 22: 1014-15.
Wainwright, D.A., Xin, J.P., Sanders, V.M., and Jones, K.J. (2009) Differential actions of pituitary adenylyl cyclase activating polypeptide and interferon gamma on Th2- and Th1-associated chemokine expression in cultured murine microglia, J. Neuroregen and Neurodegen.1:31-34.
Wainwright, D.A., Mesnard, N.A., Xin, J.P., Sanders, V.M., and Jones, K.J.(2009) Effects of facial nerve axotomy onTh2- and Th1-associated chemokine mRNA in the facial motor nucleus of wild-type and pre-symptomatic SOD1 mice., J. Neuroregen and Neurodegen., 2(1): 39-44.
Sharma, N., Marzo, S.J., Jones, K.J., and Foecking, E.M. (2009) Electrical stimulation and testosterone differentially enhance expression of regeneration-associated genes following rat facial nerve axotomy, Exp. Neurol, 223(1): 183-191.
Sharma, N., Cunningham,K., Marzo, S.J., Jones, K.J. and Foecking, E.M. (2009) Comparison of extratemporal and intratemporal facial nerve injury models, Laryngoscope, 119: 2324-2330.
Sharma, N., Coughlin, L., Porter, R.B., Tanzer, L., Wurster, R.D., Marzo, S.J.,Jones, K.J.,and Foecking, E.M. (2009) Stimulation and testosterone differentially affect rat facial nerve regenerative properties following injury Restorative Neurology Neurosci, 27:633-644.
Wainwright, D.A., Xin, J., Mesnard, N.A., Politis, C.M., Sanders, V.M. andJones, K.J. (2009) Effects of facial nerve axotomy on Th2- and Th1-associated chemokine expression in the facial motor nucleus of wild-type and pre-symptomatic mSOD1 mice. J Neuroimmun., 216:66-75.
Wainwright, D.A., Xin, J., Mesnard, N.A., Beahrs, T.R., Politis, C.M., Sanders, V.M. and Jones, K.J. (2009) Exacerbation of facial motoneuron loss after facial nerve axotomy in CCR3-deficient mice. ASN Neuro., 1(5) e00024.
Wainwright, D.A., Xin, J., Mesnard, N.A., Sanders, V.M. and Jones, K.J.(2009) Toll-like receptor 2 and facial motoneuron survival after facial nerve axotomy. Neurosci Lett., 471(1): 10-14.
Beahrs, T., Tanzer, L., Sanders, V.M. and Jones, K.J. (2009) Functional recovery and facial motoneuron survival are influenced by immunodeficiency in crush-axotomized mice. Exp. Neurol, 221(1):225-30.
Sharma, N., Moeller, C.W., Marzo, S.J., Jones, K.J., and Foecking, E.M. (2010) Combinatorial treatments enhance recovery following facial nerve crush, Laryngoscope; in press.
Mesnard, N.A., Alexander, T.D., Sanders, V.M., Jones, K.J. (2010) Use of laser microdissection in the investigation of facial motoneuron and neuropil molecular phenotypes after peripheral axotomy. Exp. Neurol., in press.
Xin, J., Sanders, V.M. and Jones, K.J. (2010) Survival of mouse facial motoneurons after facial nerve injury requires both CD4+ T cells and interleukin-10 from a non-T cell source, Brain, Beh. Immunity, in press.