SCoBIRC FACULTY

John C. Gensel, Ph.D.

Assistant Professor of Physiology
Spinal Cord and Brain Injury Research Center (SCoBIRC)

Ph.D. in Neuroscience, The Ohio State University (2007)
     Advisors: Drs. Jacqueline Bresnahan and Michael Beattie
Postdoctoral Training, The Ohio State University (2007-11)
    Advisor:  Dr. Phillip Popovich

Research Interests

Endogenous microglia and blood-borne monocytes (collectively referred to as CNS macrophages) are activated by CNS trauma and home to the site of injury. Once these cells occupy the CNS, they persist there indefinitely. This phenomenon has been documented extensively in different models of mammalian brain and spinal cord injury and is also a feature of human neurotrauma. I am interested in understanding the biological mechanisms that regulate this ubiquitous response to injury with the goal of manipulating CNS macrophages to promote repair. Ongoing studies are examining: 1) Can a pro-regenerative macrophage phenotype be induced after injury using lentiviral vectors? 2) What receptors pathways drive reparative macrophage phenotypes and can those pathways be manipulated after spinal cord injury? 3) What is the function and phenotype of macrophages responding to traumatic brain injury? 4) How does age effect the inflammatory response to neurotrauma. The goal of these studies is to develop therapies that will translate to the human population.

Gensel Laboratory Mission Statement

 The mission of the Gensel Laboratory in the Spinal Cord and Brain Injury Research Center and Department of Physiology at the University of Kentucky is to understand the cellular and molecular events resulting from neurotrauma and facilitate the development of therapies that improve the lives of individuals with traumatic brain or spinal cord injuries. Specifically, we strive for scientific excellence in order to secure funding and perform original, eminent, and reputable research in the field of neurotrauma. The goal of the lab is to maintain a productive and stimulating research environment; one in which all lab members continue to learn and advance their careers through purposeful dedication and collective team focus. Realization of this mission and goal is world-wide scientific recognition in the field of neurotrauma; successful recruitment and retention of a critical mass of laboratory staff; sufficient funding to conduct optimized experiments without financial stress; and
dissemination and prominence of former lab members.  

Techniques

Small animal surgeries including modeling traumatic brain and spinal cord injury, intraspinal/cranial microinjections, cell transplantation, track tracing; immunohistochemistry and state-of-the-art microscopy (light/fluorescence/dark-field/confocal) and image analysis (stereology); development and utilization of high-throughput, automated image analysis programs; behavioral analysis of locomotor and sensory function; cell culture (neuronal/glial/macrophage/lymphocyte); live cell imaging; macrophage and neuron phenotype and functional assays; viral vectors utilization (transformation, transfection, transduction); molecular biology (e.g., PCR,westerns).

Recent Publications

Gensel JC, Kigerl KA, Mandrekar-Colucci SS, Gaudet AD, Popovich PG. Achieving
CNS axon regeneration by manipulating convergent neuro-immune signaling. Cell
Tissue Res. 2012 Jul;349(1):201-13. Epub 2012 May 17. PubMed PMID: 22592625.

Popovich PG, Lemeshow S, Gensel JC, Tovar CA. Independent evaluation of the
effects of glibenclamide on reducing progressive hemorrhagic necrosis after
cervical spinal cord injury. Exp Neurol. 2012 Feb;233(2):615-22. Epub 2010 Dec 9.
PubMed PMID: 21145891; PubMed Central PMCID: PMC3272125.

Gensel JC, Tovar CA, Bresnahan JC, Beattie MS. Topiramate treatment is
neuroprotective and reduces oligodendrocyte loss after cervical spinal cord
injury. PLoS One. 2012;7(3):e33519. Epub 2012 Mar 13. PubMed PMID: 22428066;
PubMed Central PMCID: PMC3302770.

White RE, Rao M, Gensel JC, McTigue DM, Kaspar BK, Jakeman LB. Transforming
growth factor α transforms astrocytes to a growth-supportive phenotype after
spinal cord injury. J Neurosci. 2011 Oct 19;31(42):15173-87. PubMed PMID:
22016551; PubMed Central PMCID: PMC3213757.

Gensel JC, Donnelly DJ, Popovich PG. Spinal cord injury therapies in humans:
an overview of current clinical trials and their potential effects on intrinsic
CNS macrophages. Expert Opin Ther Targets. 2011 Apr;15(4):505-18. Epub 2011 Feb 1. Review. PubMed PMID: 21281256.

Gensel JC, Schonberg DL, Alexander JK, McTigue DM, Popovich PG. Semi-automated Sholl analysis for quantifying changes in growth and differentiation of neurons and glia. J Neurosci Methods. 2010 Jun 30;190(1):71-9. Epub 2010 May 11. PubMed PMID: 20438758; PubMed Central PMCID: PMC2911480.

Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009 Oct 28;29(43):13435-44. PubMed PMID: 19864556; PubMed Central PMCID: PMC2788152.

Donnelly DJ, Gensel JC, Ankeny DP, van Rooijen N, Popovich PG. An efficient and reproducible method for quantifying macrophages in different experimental models of central nervous system pathology. J Neurosci Methods. 2009 Jun 30;181(1):36-44. Epub 2009 Apr 23. PubMed PMID: 19393692; PubMed Central PMCID: PMC2737682.

Gensel JC, Nakamura S, Guan Z, van Rooijen N, Ankeny DP, Popovich PG. Macrophages promote axon regeneration with concurrent neurotoxicity. J Neurosci.  2009 Mar 25;29(12):3956-68. PubMed PMID: 19321792; PubMed Central PMCID: PMC2693768.

PubMed List