Scott R. Whittemore, Ph.D
Professor and Vice Chairman for Research,
Department of Neurological Surgery, Anatomical Sciences & Neurobiology
Henry D. and Marianna Garretson Endowed Chair in Spinal Cord Injury Research
Scientific Director, Kentucky Spinal Cord Injury Research Center
Spinal Cord Injury causes many changes at the molecular level that damage or destroy key components of the nervous system that carry signals to and from the brain - including neurons, axons and the myelin coating that protects the nervous system much like the insulation around an electrical cord, as well as the vascular infrastructure that carries oxygen to these tissues.
- Find strategies to replace lost neurons, help axons regenerate, and regeneration of the myelin coating around damaged or regenerating axons.
- Using undifferentiated precursor cells, gene therapies, and transplanted neurons, the lab seeks to understand the development of these key components of the vascular and nervous system at the molecular and genetic level in order to protect them from damage and/or promote their regeneration.
Amanda M. Pocratsky, Darlene A. Burke, Johnny R. Morehouse, Jason E. Beare, Amberly S. Riegler, Pantelis Tsoulfas, Gregory J. R. States, Scott R. Whittemore & David S. K. Magnuson (2017) Reversible silencing of lumbar spinal interneurons unmasks a task-specific network for securing hindlimb alternation. Nature Communications (in press)
*Kuypers NJ, *AN Bankston, RM Howard, JE Beare, SR Whittemore (2016) Remyelinating oligodendrocyte precursor cell miRNAs from the Sfmbt2 cluster promote cell cycle arrest and differentiation. J Neurosci (in press) *co-first authors
Saraswat Ohri, SA Mullins, M Hetman, SR Whittemore (2016) ATF6α deletion abrogates the ER stress response after SCI, but does not result in improved functional recovery. J Neurotrauma (in press)
Saraswat Ohri S, SA Mullins, M Hetman, SR Whittemore (2014) Inhibition of GADD34, the stress-inducible subunit of the endoplasmic reticulum stress response, does not enhance functional recovery after spinal cord injury. PLOS ONE Nov 11;9(11):e109703, PMID:25386686
Nielson JL, CF Guandique, AW Liu, DA Burke, AT Lash, R Moseanko, S Hawbecker, SC Strand, S Zdunowski, K-A. Irvine, JH Brock, YS Nout-Lomas, JC Gensel, KD Anderson, MR Segal, ES Rosenzweig, DSK Magnuson, SR Whittemore, DM McTigue, PG Popovich, AG Rabchevsky, SW Scheff, O Steward, G Courtine, VR Edgerton, MH Tuszynski, MS Beattie, JC Bresnahan, AR Ferguson (2014) Development of a database for translational spinal cord injury research. J Neurotrauma 31:1789-99
Myers SA, KR Andres, T Hagg, SR Whittemore (2014) CD36 deletion improves recovery from spinal cord injury. Exp Neurol 256:25-38 PMID: 24690303
Saraswat Ohri S, M Hetman, SR Whittemore (2013) Restoring endoplasmic reticulum homeostasis improves functional recovery after spinal cord injury. Neurobiol Dis 58C:29-37 PMID:23659896
Kuypers NJ, KT James, GU Enzmann, DSK Magnuson, SR Whittemore (2013) Functional consequences of ethidium bromide demyelination of the ventral mouse spinal cord. Exp Neurol 247:615-622 PMC3742572
Burke DA, SR Whittemore, DSK Magnuson (2013) Consequences of common data analysis inaccuracies in CNS trauma injury basic research. J Neurotrauma 30:797-805 PMID: 23186206
Hagg T, RL Benton, JA Fassbender, SR Whittemore (2012) Assessing microvessels after spinal cord injury, In: Animal Models of Acute Neurological Injuries II: Injury and Mechanistic Assessments, Volume 2 (J Chen, X-M Xu, ZC Xu, JH Zhang, eds) Springer Protocols Handbooks, Secaucus NJ, pp 625-638
Beare J, JR Morehouse, DSK Magnuson,SR Whittemore (2012) Automated gait analysis following spinal cord injury, In: Animal Models of Acute Neurological Injuries II: Injury and Mechanistic Assessments (J Chen, X-M Xu, ZC Xu, JH Zhang, eds) Springer Protocols Handbooks, Secaucus NJ, pp: 625-638
Cao Q & Whittemore SR (2012) Cell Transplantation: Stem Cells, Chapter 34, In: Handbook of Clinical Neurology, Spinal Cord Injury (Verhaagen J & McDonald JW, eds), Elsevier, Amsterdam, 109:551-61 PMID: 23098736
Fassbender JM, SA Myers, S Saraswat Ohri, MG Gruenthal, RL Benton, SR Whittemore (2012) Deletion of ER CHOP is protective in the microvasculature post-SCI. Curr Neurovasc Res 9:274-81 PMID: 22873727
Dincman TA*, JE Beare*, S Saraswat Ohri, SR Whittemore (2012) Isolation of cortical mouse oligodendrocyte precursor cells, J Neurosci Meth 209:219-26. PMC 3407963 (*co-first authors)
Zhang Y*, *YP Zhang, LBE Shields, Y Zheng, X-M Xu, SR Whittemore, CB Shields (2012) Cervical central canal occlusion induces syringomyelia. Neurosurgery (in press) (*equal contribution)
Fassbender JM, SA Myers, SR Whittemore (2011) Activating notch signaling post-SCI modulates angiogenesis in penumbral vascular beds but does not improve locomotor recovery, Exp Neurol 227:302-13 PMID: 21156172
Myers SA, WH DeVries, KR Sorg, MJ Gruenthal, RL Benton, JB Hoying, T Hagg, SR Whittemore (2011) CD47 null mice show improved recovery from spinal cord injury, Neurobiol Dis 42:21-34. PMID: 21168495
Wang Y, X Cheng, Q He, DH Kim, SR Whittemore, Q Cao (2011) Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult OPCs by increasing the expression of bone morphogenetic proteins, J Neurosci 31:6053-8 PMID:21508230
Fassbender JM, SR Whittemore, T Hagg (2011) Targeting microvasculature for neuroprotection after SCI. Neurotherapeutics 8:240-251 PMID: 21360237
Saraswat Ohri S, MA Maddie, Y Zhao, MS Qiu, M Hetman, SR Whittemore (2011) Attenuating the ER stress response after SCI improves functional recovery, Glia 59:1489-502
Yu P, Y-P Zhang, LBE Shields, Y Zheng, X Hu, R Hill, RM Howard, Z Gu, DA Burke, SR Whittemore, X-M Xu, CB Shields (2011) Inhibitor of DNA binding 2 promotes axonal growth after SCI, Exp Neurol 231:38-44
Zhu Q, SR Whittemore, WH DeVries, X Zhao, NJ Kuypers, M Qiu (2011) Dorsally-derived oligodendrocytes in the spinal cord contribute to axonal myelination during development and remyelination following focal demyelination. Glia 59:1612-21 PMID:21679705
Saraswat Ohri S, MA Maddie, Y Zhang, CB Shields, M Hetman, SR Whittemore (2011) Deletion of the pro-apoptotic endoplasmic reticulum stress response effector CHOP does not result in improved locomotor function after severe contusive spinal cord injury.J Neurotrauma 29:579-88 PMID: 21933012
Myers SA, WH DeVries, MJ Gruenthal, KR Andres, SR Whittemore (2011) Sildenafil improves epicenter vascular perfusion but not hindlimb functional recovery after contusive spinal cord injury. J Neurotrauma 29:528-38 PMID: 21970599
Zhang Y, Y Zheng, YP Zhang, Y Ping, LBE Shields, X Hu, P Yu, DA Burke, H Wang, C Jun, J Byers, SR Whittemore, CB Shields (2010) Enhanced adenoviral gene delivery to motor neurons and dorsal root ganglion neurons following injection into partially demyelinated peripheral nerve, J Neurosci Res 88:2374-84
Mozer AB, SR Whittemore, RL Benton (2010) Spinal microvascular expression of PV-1 is associated with inflammation and blood-spinal cord barrier pathology post-SCI, Curr Neurovasc Res 7:238-250
Cao Q, Q He, Y Wang, X Cheng, RM Howard, Y Zhang, CB Shields, WH DeVries, DSK Magnuson, X-M Xu, SR Whittemore (2010) Transplantation of CNTF-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury, J Neurosci
Han S, SD Sithu, ET Mahoney, RL Benton, MM Maddie, SE D’Sousa, SR Whittemore, T Hagg (2010) An αvβ3 integrin agonist reduces leukocyte transmigration and rescues blood vessels, myelin and function after spinal cord contusion in adult mice. Brain
Beare JE, JR Morehouse, WH DeVries, GU Enzmann, DA Burke, DSK Magnuson, SR Whittemore (2009) Gait analysis in normal and spinal contused mice using the TreadScan® system. J Neurotrauma 26:2045-2056
Benton RL, MA Maddie, MJ Gruenthal, T Hagg, SR Whittemore (2009) Neutralizing endogenous VEGF following spinal cord injury modulates adaptive angiogenesis but not tissue sparing or functional recovery. Curr Neurovascular Res 6:124-131
Benton RL, MA Maddie, TA Dincman, T Hagg, SR Whittemore (2009) Transcriptional activation of spinal microvascular endothelial cells by TGF-1 occurs concomitant with acute neurovascular unit plasticity following focal gray matter ischemia-reperfusion spinal cord injury. ASN Neuro (http://www.asnneuro.org/an/001/e015/001e015.pdf) (doi:10.1042/AN20090008)
Hill RL, YP Zhang, Y Han, DA Burke, WH DeVries, SR Whittemore, CB Shields (2009) Anatomical and functional outcomes following a precise, graded dorsal laceration spinal cord injury in C57Bl/6 mice, J Neurotrauma 26:1-15 (doi:10:1089/neu.2008.0543)
Kirschner DA, RL Avila, A Luoma, GU Enzmann, D Agrawal, H Inouye, MB Bunge, J Kocsis, A Peters, SR Whittemore (2009) Rapid assessment of internodal myelin in fixed tissue from animal models,J Neurosci Res 88:712–723 (doi: 10.1002/jnr.22241)
Ma Z, Q Cao, L Zhang, GU Enzmann, P Lu, SR Whittemore, X-M Xu (2009) Oligodendrocyte precursor cells differentially expressing Nogo-A but not MAG are more permissive to neurite outgrowth than mature oligodendrocytes,Exp Neurol 17:184-96
Mahoney ET, RL Benton, MA Maddie, SR Whittemore, T Hagg (2008) ADAM8 is selectively upregulated in endothelial cells and is associated with angiogenesis after spinal cord injury in adult mice. J Comp Neurol 512:243-55 (doi: 10.1002/cne.21902)
Zhang YP, DA Burke, LBE Shields, SY Chekmenev, T Dincman, Y Zhang, Y Zheng, RR Smith, RL Benton, WH DeVries, X Hu, DSK Magnuson, SR Whittemore, CB Shields (2008) Combined assessment to discriminate small functional differences following spinal cord contusion based on precise vertebral stabilization and tissue displacement, J Neurotrauma 25:1227-1240 (doi:10:1089/neu.2007.0388)
Benton RL, MA Maddie, CA Worth, E Mahoney, T Hagg, SR Whittemore (2008) Transcriptomic screening of microvascular endothelial cells implicates novel molecular regulators of vascular dysfunction following spinal cord injury. J Cereb Blood Flow Metab 28:1771-1785 (doi:10.1038/jcbfm.2008.76)
Benton RL, MA Maddie, DR Minnillo, T Hagg, SR Whittemore (2008) Identification and characterization of a specific subpopulation of angiogenic spinal microvessels binding the Griffonia simplicifolia isolectin B4 following traumatic spinal cord injury (SCI) in the adult mouse.J Comp Neurol 507:1031-1052
Cheng X, Y Wang, Q He, M Qiu, SR Whittemore, Q Cao, Down-regulation of Olig1 and Olig2 by BMP2 inhibits the differentiation and maturation of adult oligodendrocyte precursor cells (2007) Stem Cells 25:3204-14 (doi: 10.1634/stemcells.2007-0284)
Cruz-Orengo L, JD Figueroa, A Torrado, A Puig, SR Whittemore & JD Miranda (2007) Reduction of EphA4 receptor expression after spinal cord injury does not induce axonal regeneration or return of tcMMEP responses, Neurosci Letts 418:49-54
Talbott JF, Q Cao, J Bertran, M Nkansah, RL Benton, E Lavik & SR Whittemore (2007) CNTF promotes the survival and differentiation of adult spinal cord-derived oligodendrocyte precursor cells in vitro but fails to promote remyelination in vivo, Exp Neurol 204:485-489
Willson CA, RD Foster, SM Onifer, SR Whittemore* & JD Miranda* (2006) EphB3 receptor and its ligand expression in the adult rat brain, J Molec Histol 37:369-80 (*co-communicating authors)
Cruz-Orengo L, JD Figueroa, I Velàzquez, A Torrado, C Ortìz, C Hernàndez, A Puig, A Segarra, SRWhittemore & JD Miranda (2006) Blocking EphA4 upregulation after spinal cord injury results in enhanced chronic pain. Exp Neurol 202:421-33
Abdellatif AA, Pelt JL, Benton RL, Howard RM, Tsoulfas P, Ping P, Xu XM, Whittemore SR (2006) Gene delivery to the spinal cord: Comparison between lentiviral, adenoviral, and retroviral vector delivery systems, J Neuro Res 84:000-000 (Page Proofs)
Cruz-Orengo L, Figueroa JD, Velazquez I, Torrado A, Ortiz C, Hernandez C, Puig A, Segarra A, Whittemore SR, Miranda JD (2006) Blocking EphA4 upregulation after spinal cord injury results in enhanced chronic painExp Neurology (Page Proofs)
Figueroa JD, Benton RL, Velazquez I, Torrado AI, Ortiz CM, Henandez CM, Diaz JJ, Magnuson DS, Whittemore SR, Miranda JD (2006) Inhibition of EphA7 up-regulation after spinal cord injury reduces apoptosis and promotes locomotor recovery J Neuro Res
Talbott JF, Cao WL, Enzmann GU, Benton RL, Achim V, Cheng XX, Mills MD, Rao MS, Whittemore SR (2006) Schwann cell-like differentiation by adult oligodendrocyte precursor cells following engraftment into the demyelinated spinal cord is BMP-dependent, Glia 54: 147-159
Benton RL, JP Woock, M Hetman, E Gozal, SR Whittemore: Intraspinal application of endothelin results in focal ischemic injury of spinal gray matter and restricts the differentiation of engrafted neural stem cells, Neurochem Res 30:809-823, 2005.
Cao Q, Xu X-M, DeVries WH, Enzmann GU, Ping P, Wood PM, Tsoulfas P, Bunge MB, Whittemore SR (2005) Functional recovery in traumatic spinal cord injury following transplantation of multineurotrophin-expressing glial precursor cells. J Neurosci 25:6947-6957
Enzmann GU*, RL Benton*, JP Woock, RM Howard, P Tsoulfas & SR Whittemore (2005) Consequences of noggin expression by glial and neuronal precursor cells engrafted into the injured spinal cord.Exp Neurol 195:293-304 (*these two authors contributed equally)
Cao Q, YP Zhang, C Iannotti, WH DeVries, XM Xu, CB Shields & SR Whittemore (2005) Functional and electrophysiological consequences of graded contusive spinal cord injury in the adult rat, Exp Neurol 191:S3-S16
Benton RL, GU Enzmann & SR Whittemore (2005) Stem cell grafting into the injured spinal cord, In: Synaptic Plasticity, M Baudry, Y Bi, S Schreiber, eds., Marcel Dekker, New York, pp 329-359
Loy DN, AE Sroufe, JL Pelt, DA Burke, Q-l Cao, JF Talbott & SR Whittemore (2005) Serum biomarkers for acute spinal cord injury: rapid elevation of neuron-specific enolase and S-100á, Neurosurgery 56:391-397
Talbott JF, DN Loy, Y Liu, MS Qiu, MB Bunge, MS Rao & SR Whittemore (2005) Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes, Exp Neurol 192:11-24
Gajavelli S, Wood PM, Pennica D, Whittemore SR, Tsoulfas, P: BMP signaling initiates a neural crest differentiation program in embryonic rat CNS stem cells. Exp Neurol 188: 205-223, 2004.
Loy DN, Magnuson DSK, Zhang YP, Onifer SM, Mills MD, Cao QL, Darnall JB, Fajardo LC, Burke DA, Whittemore SR: Functional redundancy of ventral spinal locomotor pathways. J Neurosci 22:315-323, 2002.
Loy DN, Crawford CH, Darnall JB, Burke DA, Onifer SM, Whittemore SR: Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat.J Comp Neurol 445:308-324, 2002.
Willson CA, Irizarry-Ramírez M, Gaskins HE, Cruz-Orengo L, Figueroa JD, Whittemore SR, Miranda JD: Upregulation of EphA receptor expression in the injured adult rat spinal cord. Cell Transplant 11:229-239, 2002.
Cao QL, Onifer SM, Whittemore SR: Labeling stem cells in vitro for identification of their differentiated phenotypes after grafting into the CNS. In: Methods in Molecular Biology, vol 198: Neural Stem Cells: Methods and Protocols, Zigova T, Sanberg PR, Sanchez-Ramos J (eds). Humana Press, Totowa, NJ. Chapter 28, pp 307-318, 2002.
Whittemore SR, Zhang YP, Shields CB, Magnuson DSK: Optimizing stem cell grafting into the CNS. Ibid, Chapter 29, pp 319-325, 2002.
Loy DN, JF Talbott, SM Onifer, MD Mills, DA Burke, JB Darnall, LC Farajdo, DSK Magnuson & SR Whittemore: Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat, Exp Neurol 177:575-580, 2002
Yang P, Seiler MJ, Aramant RB, Whittemore SR: In vitro isolation and expansion of human retinal progenitor cells. Exp Neurol 177:326-331, 2002.
Cao Q-L, Howard RM, Dennison, JB, Whittemore SR: Differentiation of engrafted neuronal restricted precursor cells is inhibited in the traumatically injured spinal cord. Exp Neurol 177:349-359, 2002