Department of Psychology
Department of Psychology

Linda Noble


ProfessorPh.D., University of Texas at Austin

Linda Noble

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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.

 

Publications


SELECTED PUBLICATIONS

Hsu JY, Bourguignon LY, Adams CM, Peyrollier K, Zhang H, Fandel T, Cun CL, Werb Z, Noble-Haeusslein LJ. Matrix metalloproteinase-9 facilitates glial scar formation in the injured spinal cord. J Neuroscience. 28:13467-77, 2008.

Lee SM, Rosen S, Weinstein P, van Rooijen N, Noble-Haeusslein LJ. Prevention of both neutrophil and monocytes recruitment promotes recovery after spinal cord injury.  J. Neurotrauma.  28:1893-907, 2011

Zhang H, Trivedi A, Lee J, Lohela M, Lee, SM, Fandel T, Werb Z, and Noble-Haeusslein LJ.  Matrix metalloproteinase-9 and stromal cell-derived factor-1 act synergistically to support migration of blood borne monocytes into the injured spinal cord.  J. Neuroscience. 2:15894-903, 2011

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

Semple BD, Blomgren K, Gimlin K, Ferriero DF, and Noble-Haeusslein LJ.  Brain development in rodents and humans:  Identifying benchmarks of maturation and vulnerability to injury across species.  Progress in Neurobiology. 107:1-16, 2013

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. 38:220-238, 2016.

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. 19:544-557, 2016.

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. 284(Pt A):50-62, 2016

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. 114:4969-4974, 2017

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. 12:e0170512, 2017 .

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 of Neurotrauma, In Press.

Curriculum Vitae


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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