Department of Psychology
Department of Psychology

Linda Noble


ProfessorPh.D., University of California, Los Angeles

Linda Noble

Contact

Interests


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

Biography


The Noble-Haeusslein laboratory is focused on translational research in the field of neurotrauma. Th 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. Emphasis is on how a traumatic injury influences the blood-brain/spinal cord barrier and the pathways by which bone-marrow derived leukocytes enter the CNS after injury and impose time and context dependent modulation of secondary injury and recovery events.  This multifaceted approach has led to the discovery of new pharmacologic (matrix metalloproteinase inhibitors and L-selectin sheddases) 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 studies of traumatic injury to the developing murine 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, driven in part by polymorphonuclear leukocytes and Syk signaling, that give rise to long-term cognitive/social 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 a new preclinical model of mild traumatic injury to the ferret brain, where there will be opportunity to study how a gyrencephalic adolescent brain responds to trauma, focusing on patterns of barrier disruption, indices of early and delayed cell injury, and behavioral recovery.

Courses


UGS 302 • Brain Injury From Wwi To Nfl

60375 • Fall 2019
Meets TTH 12:30PM-2:00PM SEA 4.242
Wr ID

Title:  Brain Injury: From WWI to the NFL

Semester:  2019 Fall

Meets:  TTh 2:00pm-3:30PM SEA 4.242

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)  

Munji RN, Soung AL, Weiner GA, Sohet F, Semple BD, Trivedi A, Gimlin K, Kotoda M, Korai M, Aydin S, Batugal A, Cabangcala AC, Schupp PG, Oldham MC, Hashimoto T, Noble-Haeusslein LJ, Daneman R. Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module. Nat Neurosci. 2019 Nov;22(11):1892-1902. doi: 10.1038/s41593-019-0497-x. Epub 2019 Oct 14. PubMed PMID: 31611708; PubMed Central PMCID: PMC6858546.

Trivedi A, Noble-Haeusslein LJ, Levine JM, Santucci AD, Reeves TM, Phillips LL. Matrix metalloproteinase signals following neurotrauma are right on cue. Cell Mol Life Sci. 2019 Aug;76(16):3141-3156. doi: 10.1007/s00018-019-03176-4. Epub 2019 Jun 6. Review. PubMed PMID: 31168660.

von Leden RE, Parker KN, Bates AA, Noble-Haeusslein LJ, Donovan MH. The emerging role of neutrophils as modifiers of recovery after traumatic injury to the developing brain. Exp Neurol. 2019 Jul;317:144-154. doi: 10.1016/j.expneurol.2019.03.004. Epub 2019 Mar 12. Review. PubMed PMID: 30876905; PubMed Central PMCID: PMC6544477.

DeWitt DS, Hawkins BE, Dixon CE, Kochanek PM, Armstead W, Bass CR, Bramlett HM, Buki A, Dietrich WD, Ferguson AR, Hall ED, Hayes RL, Hinds SR, LaPlaca MC, Long JB, Meaney DF, Mondello S, Noble-Haeusslein LJ, Poloyac SM, Prough DS, Robertson CS, Saatman KE, Shultz SR, Shear DA, Smith DH, Valadka AB, VandeVord P, Zhang L. Pre-Clinical Testing of Therapies for Traumatic Brain Injury. J Neurotrauma. 2018 Dec 1;35(23):2737-2754. doi: 10.1089/neu.2018.5778. Epub 2018 Aug 30. PubMed PMID: 29756522.

McCreedy DA, Lee S, Sontag CJ, Weinstein P, Olivas AD, Martinez AF, Fandel TM, Trivedi A, Lowell CA, Rosen SD, Noble-Haeusslein LJ. Early Targeting of L-Selectin on Leukocytes Promotes Recovery after Spinal Cord Injury, Implicating Novel Mechanisms of Pathogenesis. eNeuro. 2018 Jul-Aug;5(4). doi: 10.1523/ENEURO.0101-18.2018. eCollection 2018 Jul-Aug. PubMed PMID: 30225356; PubMed Central PMCID: PMC6140118.

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. 2018 Mar 15;340:165-171. doi: 10.1016/j.bbr.2016.09.013. Epub 2016 Sep 8. PubMed PMID: 27614007; PubMed Central PMCID: PMC5342952.

Levine JM, Cohen ND, Fandel TM, Levine GJ, Mankin J, Griffin JF, Kerwin SC, Boudreau CE, Trivedi A, Noble-Haeusslein LJ. Early Blockade of Matrix Metalloproteinases in Spinal-Cord-Injured Dogs Results in a Long-Term Increase in Bladder Compliance. J Neurotrauma. 2017 Sep 15;34(18):2656-2667. doi: 10.1089/neu.2017.5001. Epub 2017 Jul 27. PubMed PMID: 28520505.

Semple BD, O'Brien TJ, Gimlin K, Wright DK, Kim SE, Casillas-Espinosa PM, Webster KM, Petrou S, Noble-Haeusslein LJ. Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain. J Neurosci. 2017 Aug 16;37(33):7864-7877. doi: 10.1523/JNEUROSCI.0982-17.2017. Epub 2017 Jul 19. PubMed PMID: 28724747; PubMed Central PMCID: PMC5559762.

Moore SA, Granger N, Olby NJ, Spitzbarth I, Jeffery ND, Tipold A, Nout-Lomas YS, da Costa RC, Stein VM, Noble-Haeusslein LJ, Blight AR, Grossman RG, Basso DM, Levine JM. Targeting Translational Successes through CANSORT-SCI: Using Pet Dogs To Identify Effective Treatments for Spinal Cord Injury. J Neurotrauma. 2017 Jun 15;34(12):2007-2018. doi: 10.1089/neu.2016.4745. Epub 2017 Mar 22. Review. PubMed PMID: 28230415; PubMed Central PMCID: PMC5467140.

Butts JC, McCreedy DA, Martinez-Vargas JA, Mendoza-Camacho FN, Hookway TA, Gifford CA, Taneja P, Noble-Haeusslein L, McDevitt TC. Differentiation of V2a interneurons from human pluripotent stem cells. Proc Natl Acad Sci U S A. 2017 May 9;114(19):4969-4974. doi: 10.1073/pnas.1608254114. Epub 2017 Apr 24. PubMed PMID: 28438991; PubMed Central PMCID: PMC5441696.

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;12(1):e0170512. doi: 10.1371/journal.pone.0170512. eCollection 2017. PubMed PMID: 28122028; PubMed Central PMCID: PMC5266300.

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. doi: 10.1021/acschemneuro.6b00217. Epub 2016 Aug 25. PubMed PMID: 27551907.

Fandel TM, Trivedi A, Nicholas CR, Zhang H, Chen J, Martinez AF, Noble-Haeusslein LJ, Kriegstein AR. Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury. Cell Stem Cell. 2016 Oct 6;19(4):544-557. doi: 10.1016/j.stem.2016.08.020. Epub 2016 Sep 22. PubMed PMID: 27666009; NIHMSID:NIHMS824188.

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 Oct;284(Pt A):50-62. doi: 10.1016/j.expneurol.2016.07.018. Epub 2016 Jul 25. PubMed PMID: 27468657; PubMed Central PMCID: PMC5035216.

Semple BD, Sadjadi R, Carlson J, 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. doi: 10.1159/000448089. Epub 2016 Aug 23. PubMed PMID: 27548472.

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 Mar 3. Review. PubMed PMID: 26949224; PubMed Central PMCID: PMC5627971.

Bajwa NM, Halavi S, Hamer M, Semple BD, Noble-Haeusslein LJ, 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;11(1):e0146886. doi: 10.1371/journal.pone.0146886. eCollection 2016. PubMed PMID: 26796696; PubMed Central PMCID: PMC4721654.

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. Review. PubMed PMID: 27604726.

Semple BD, Noble-Haeusslein LJ, Gooyit M, Tercovich KG, Peng Z, Nguyen TT, 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;10(11):e0143386. doi: 10.1371/journal.pone.0143386. eCollection 2015. PubMed PMID: 26588471; PubMed Central PMCID: PMC4654502.

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. doi: 10.1089/neu.2014.3861. Epub 2015 Aug 27. PubMed PMID: 26058402; PubMed Central PMCID: PMC4651035.

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. 2015 Nov;58:123-46. doi: 10.1016/j.neubiorev.2014.12.004. Epub 2014 Dec 10. Review. PubMed PMID: 25496906; PubMed Central PMCID: PMC4465064.

Semple BD, Lee S, Sadjadi R, Fritz N, Carlson J, Griep C, Ho V, Jang P, Lamb A, Popolizio B, Saini S, Bazarian JJ, Prins ML, Ferriero DM, Basso DM, Noble-Haeusslein LJ. Repetitive concussions in adolescent athletes - translating clinical and experimental research into perspectives on rehabilitation strategies. Front Neurol. 2015;6:69. doi: 10.3389/fneur.2015.00069. eCollection 2015. Review. PubMed PMID: 25883586; PubMed Central PMCID: PMC4382966.

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. 2015 Feb;74:263-80. doi: 10.1016/j.nbd.2014.12.003. Epub 2014 Dec 9. PubMed PMID: 25497734; PubMed Central PMCID: PMC4323771.

For a full list of publications, please refer to:

https://www.ncbi.nlm.nih.gov/myncbi/linda.noble.1/bibliography/public/

 


  •   Map
  • Department of Psychology

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