Department of Psychology
Department of Psychology

Linda Noble


ProfessorPh.D., University of Texas at Austin

Linda Noble

Contact

Interests


Immune-based mechanisms as determinants of long-term recovery after pediatric brain and spinal cord injuries and environmental factors that shape the recovery processes.

Biography


My laboratory is focused on translational research in the field of neurotrauma. Our overarching long-term objective is to develop targeted therapeutics that will improve recovery after traumatic spinal cord and pediatric brain injuries. This research relies on cellular, molecular, and behavioral tools to identify key mechanisms underlying early cell injury that impair recovery processes in preclinical models of neurotrauma. This multifaceted approach has led to the discovery of new pharmacologic and stem-cell based therapeutics that ameliorate several key features of spinal cord injury; namely, bladder and locomotor dysfunction and central neuropathic pain.

Similar progress has been made in our studies of traumatic injury to the pediatric brain. Traumatic brain injuries (TBIs) are the leading cause of death and disability in children and there is growing concern that even mild forms of TBIs including concussions may have long-term adverse consequences. We have found that age at time of injury is predictive of recovery in brain injured rodents, with younger ages showing less resilience to the injury with more profound long-term deficits in cognition and sociability. These studies have led to the discovery of unique, age-dependent immune-based signatures that give rise to long-term cognitive deficits. Importantly, these deficits can be rescued by either genetic or pharmacologic approaches that target the early innate immune response.

Most recently, we have turned our attention to several new areas of research. These include a novel model of concussion to the gyrencephalic adolescent brain where the early immune response may render the brain more vulnerable to repeat insults.  In addition, we are addressing the cross-talk between the injured pediatric brain and the microbiome which may give rise to long-term changes in social behaviors.

 

Courses


PSY 394P • Brain/Spinal Cord Injuries

42929 • Spring 2018
Meets TTH 12:30PM-2:00PM SEA 2.116

This course is centered on translational research, focusing on traumatic brain and spinal cord injuries.  Participants will learn about 1) clinical presentations, medical/surgical management, and outcomes, 2) preclinical modelling that is used for discovery, and 3) strategies aimed at restoration of cognitive and motor/sensory function.

Publications


PEER REVIEWED PUBLICATIONS  (Last 5 years)  

  1. Landis SC, et al.  A call for transparent reporting to optimize the predictive value of preclinical research.  Nature. 490:187-9, 2012
  2. Semple BD, Canchola SA, and Noble-Haeusslein LJ.  Deficits in social behavior emerge during development after pediatric brain injury in mice.  J Neurotrauma. 29:2672-83, 2012
  3. Lapchak PA, Zhang JH, and Noble-Haeusslein LJ.  Rigor guidelines:  Escalating stairs and steps for effective translational research.  Translational Stroke Research.4:279-285, 2013
  4. Semple BD, Blomgren K, Gimlin K, Ferriero DF, Noble-Haeusslein.  Brain development in rodents and humans:  Identifying benchmarks of maturation and vulnerability to injury across species.  Progress in Neurobiology. 107:1-16, 2013
  5. Hansen CH, Fisher LC, Dibert RJ Jakeman L, Zhang H, Noble-Haeusslein LJ, White S, Basso DM.  Elevated MMP-9 in the lumbar cord early after thoracic spinal cord injury impedes motor relearning in mice.  Journal of Neuroscience. 33:13101-11, 2013
  6. Chen CY, Noble-Haeusslein LJ, Ferriero, DM, Semple BD.  Traumatic injury to the immature frontal lobe.  A new murine modle of long-term motor impairment in the absence of psychosocial or cognitive deficits.  Developmental Neuroscience. 35:474-90, 2013
  7. Bondi CO, Semple BD, Noble-Haeusslein LJ, Osier ND, Carlson SW, Dixon CE, Giza CC, Kline AE. Found in translation:  Understanding the biology and behavior of experimental traumatic brain injury.  Neurosci Biobehav Rev.  Dec 10. pii: S0149-7634(14)00335-2. doi: 10.1016/j.neubiorev.2014.12.004
  8. Semple BD, Noble-Haeusslein LJ, Jun Kwon Y, Sam PN, Gibson AM, Grissom S, Brown S, Adahman Z, Hollingsworth CA, Kwakye A, Gimlin K, Wilde EA, Hanten G, Levin HS, Schenk AK.  Sociosexual and communication deficits after traumatic injury to the developing murine brain. PLoS One. 2014 Aug 8;9(8):e103386. doi: 10.1371/journal.pone.0103386. eCollection, 2014.
  9. Levine JM, Cohen ND, Heller M, Fajt VR, Levine GJ, Kerwin SC, Trivedi AA, Fandel TM, Werb Z, Modestino A, Noble-Haeusslein LJ. Efficacy of a metalloprotinease inhibitor in spinal cord injured dogs. PLoS One. 2014 May 1;9(5):e96408. doi: 10.1371/journal.pone.0096408. eCollection, 2014.
  10. Semple BD, Trivedi A, Gimlin K, Noble-Haeusslein LJ. Neutrophil elastase mediates acute pathogenesis and is a determinant of long-term behavioral recovery after traumatic injury to the immature brain.Neurobiol Dis.74:263-80, 2015
  11. Semple BD, Haeusslein LJ, Gooyit M,Tercovich KG, Peng A , Valerie A, Schroeder VA, Suckow MA, Chang M, Raber J, Trivedi A.  Early gelatinase activity is not a determinant of long-term recovery after traumatic brain injury in the immature mouse.  PLoS One. 2015 Nov 20;10(11):e0143386. doi: 10.1371/journal.pone.0143386. eCollection 2015.
  12. Smith DH, Hicks RR, Johnson VE, Bergstrom DA, Cummings DM, Noble LJ, Hovda D, Whalen M, Ahlers ST, LaPlaca M, Tortella FC, Duhaime AC, Dixon CE.  Pre-Clinical Traumatic Brain Injury Common Data Elements: Toward a Common Language Across Laboratories. J Neurotrauma. 2015 Nov 15;32(22):1725-35.
  13. Bajwa NM, Halavi S,Hamer M, Noble-Haeusslein LJ, Semple BD, Baghchechi M, Hiroto A,. Hartman RE,.Obenaus A. Mild Concussion, but Not Moderate Traumatic Brain Injury, is Associated With Long-Term Depression-like Phenotype in Mice.  PLoS One. 2016 Jan 21;11(1):e0146886.
  14. Ryan NP, Catroppa C, Godfrey C, Noble-Haeusslein LJ, Shultz SR, O'Brien TJ, Anderson V, Semple BD.  Social dysfunction after pediatric traumatic brain injury: a translational perspective.  Neurosci Biobehav Rev. 2016 May;64:196-214. doi: 10.1016/j.neubiorev.2016.02.020. Epub 2016
  15. Trivedi A, Zhang H, Ekeledo A, Lee S, Werb Z, Plant GW, Noble-Haeusslein LJ. Deficiency in matrix metalloproteinase-2 results in long-term vascular instability and regression in the injured mouse spinal cord./ Exp Neurol. 2016 Jul 25;284(Pt A):50-62. doi: 10.1016/j.expneurol.2016.07.018. [Epub ahead of print]
  16. Semple BD,  Sadjadi R, Carlson, Chen Y, Xu D, Ferriero DM, Noble-Haeusslein LJ. Long-term anesthetic-dependent hypoactivity after repetitive mild traumatic brain injuries in adolescent mice. Dev Neurosci. 2016;38(3):220-238.
  17. Gao M, Zhang H, Trivedi A, Mahasenan KV, Schroeder VA, Wolter WR, Suckow MA, Mobashery S, Noble-Haeusslein LJ, Chang M. Selective Inhibition of MMP-2 Does Not Alter Neurological Recovery after Spinal Cord Injury. ACS Chem Neurosci. 2016 Aug 25. [Epub ahead of print]
  18. Neumann M, Liu W, Sun C, Yang SY, Noble-Haeusslein LJ, Liu J.Training of the impaired forelimb after traumatic brain injury enhances hippocampal neurogenesis in the Emx1 null mice lacking a corpus callosum.Behav Brain Res. 2016 Sep 8. pii: S0166-4328(16)30596-4. doi: 10.1016/j.bbr.2016.09.013. [Epub ahead of print]
  19. Semple BD, Carlson J, Noble-Haeusslein LJ.Pediatric Rodent Models of Traumatic Brain Injury. Methods Mol Biol. 2016;1462: 325-43. doi: 10.1007/978-1-4939-3816-2_18
  20. Faber J, Wilde EA, Hanten G, Ewing-Cobbs, Aitken, ME, Yallampalli R, MacLeod MC, Mullins SH, Chu ZD, Hunger JV, Noble-Haeusslein L, Levin HS.  Ten-year outcome of early childhood traumatic brain injury:  Diffusion tensor imaging of the ventral striatum in relation to executive function.  Brain Injury. Brain Inj. 2016;30(13-14):1635-1641
  21. Fandel TM, Trivedi A A, Nicholas CR, Zhang H, Chen Jiadong, Martinez AF, Noble-Haeusslein LJ, Kriegstein AR. Human medial ganglionic eminence-like cells ameliorate neuronal hyperexcitability in the injured spinal cord. Cell Stem Cell. 2016 Oct 6;19(4):544-557. doi: 10.1016/j.stem.2016.08.020
  22. Gao M, Zhang H, Trivedi A, Mahasenan KV, Schroeder VA, Wolter WR, Suckow MA, Mobashery S, Noble-Haeusslein LJ, Chang M. Selective Inhibition of MMP-2 Does Not Alter Neurological Recovery after Spinal Cord Injury. ACS Chem Neurosci. 2016 Nov 16;7(11):1482-1487.
  23. Trivedi A, Zhang H, Ekeledo A, Lee S, Werb Z, Plant GW, Noble-Haeusslein LJ. Exp Neurol. Deficiency in matrix metalloproteinase-2 results in long-term vascular instability and regression in the injured mouse spinal cord.2016 Oct;284(Pt A):50-62. doi: 10.1016/j.expneurol.2016.07.018.
  24. Whetstone WD, Walker B, Trivedi A, Lee S, Noble-Haeusslein LJ, Hsu JC.  Protease-Activated Receptor-1 Supports Locomotor Recovery by Biased Agonist Activated Protein C after Contusive Spinal Cord Injury. PLoS One. 2017 Jan 25;12(1): e0170512. doi: 10.1371/journal.pone.0170512
  25.  Moore SA, Granger N, Olby N, Spitzbarth I, Jeffery ND, Tipold A, Nout-Lomas YS, da Costa R, Stein V, Noble-Haeusslein L, Blight AR, Grossman R, Basso DM Ed D Pt, Levine JM. Targeting translational successes through CANSORT-SCI: using pet dogs to identify effective treatments for spinal cord injury. J Neurotrauma. 2017 Feb 23. doi: 10.1089/neu.2016.4745. [Epub ahead of print]
  26. Butts JC, McCreedy DM, Mendoza-Camacho N, Hookway TA, Taneja P, Noble-Haeusslein LJ, McDevitt TC.  Differentiation of V2a interneurons from human pluripotent stem cells Proc Natl Acad Sci U S A. May 9;114(19):4969-4974. doi: 10.1073/pnas.1608254114
  27. L Levine J, Cohen ND, Fandel TM, Levine GJ, Mankin J, Griffin JF, Kerwin SC, Boudreau CE, Trivedi AT, Noble-Haeusslein LJ.  Early blockade of matrix metalloproteinases in spinal cord injured dogs results in a long-term increase in bladder compliance.  Journal Journal of Neurotrauma, J Neurotrauma. 2017 Sep 15;34(18):2656-2667. doi: 10.1089/neu.2017.5001.
  28. Semple BD, O’Brien TJ, Gimlin K, Wright DK ple BD, O'Brien TJ, Gimlin K, Wright DK, Kim SE, Casillas-Espinosa PM, Webster KM, Petrou S, Noble-Haeusslein LJ.  Interleukin-receptor in seizure susceptibility after traumatic injury in the pdiatric brain.  J Neurosci. Aug 16;37(33):7864-7877. doi: 10.1523/JNEUROSCI.0982-17.2017.

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    The University of Texas at Austin
    SEA 4.208
    108 E. Dean Keeton Stop A8000
    Austin, TX 78712-1043
    512-471-1157