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Linda J Noble
Professor, Professor of Neurology
Department of Psychology, Department of NeurologyThe Noble-Haeusslein laboratory studies cellular and molecular determinants of recovery after traumatic brain and spinal cord injuries.linda.noble@austin.utexas.edu
Phone: 512-495-5250
Office Location
SEA 5.226
Postal Address
108 E DEAN KEETON ST
AUSTIN, TX 78712-
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 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 traumatic injury to the ferret brain, where there will be opportunity to study how a young gyrencephalic brain responds to trauma, focusing on mechanisms underlying barrier disruption and its regional specificity, indices of early and delayed cell injury, and early determinants of behavioral recovery.
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PUBLICATIONS OVER THE PAST 5 YEARS
- 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.
- 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.
- 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.
- 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, 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.
- 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;9(8):e103386. doi: 10.1371/journal.pone.0103386. eCollection 2014. PubMed PMID: 25106033; PubMed Central PMCID: PMC4126664.
- Chen CY, Noble-Haeusslein LJ, Ferriero D, Semple BD. Traumatic injury to the immature frontal lobe: a new murine model of long-term motor impairment in the absence of psychosocial or cognitive deficits. Dev Neurosci. 2013;35(6):474-90. doi: 10.1159/000355874. Epub 2013 Nov 16. PubMed PMID: 24247103; PubMed Central PMCID: PMC3923401.
- Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol. 2013 Jul-Aug;106-107:1-16. doi: 10.1016/j.pneurobio.2013.04.001. Epub 2013 Apr 11. Review. PubMed PMID: 23583307; PubMed Central PMCID: PMC3737272.
https://www.ncbi.nlm.nih.gov/labs/bibliography/linda.noble.1/bibliography/public/
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