Photo of Jodi L. McBride, Ph.D.

Jodi L. McBride Ph.D.

  • (503) 346-5454
    • Assistant Professor Oregon National Primate Research Center
    • Assistant Professor of Behavioral Neuroscience School of Medicine
    • Behavioral Neuroscience Graduate Program School of Medicine
    • Neuroscience Graduate Program School of Medicine

The McBride Laboratory focuses on finding therapies for the neurodegenerative brain disorder, Huntington's disease (HD).  HD is a fatal, genetic neurodegenerative disorder caused by a mutation on chromosome 4.  The genetic mutation (CAG repeat) in the HTT gene encodes a mutant huntingtin protein (HTT) with an expanded polyglutamine stretch at the N-terminus of the protein. The characteristic hallmarks of HD neuropathology include mutant HTT-containing aggregates and robust cell loss in numerous regions throughout the brain, such as the striatum (comprised of the caudate nucleus and putamen) cortex, thalamus, hypothalamus and the substantia nigra. Clinically, the most obvious symptoms of HD involve involuntary hyperkinetic movements of the arms, legs, and face, known as chorea.  Additionally, HD patients suffer from cognitive deficits, particularly those involving working (short-term) memory, and personality changes including emotional disturbances such as depression, anxiety, impulsivity and apathy.

Currently, projects in the McBride Laboratory focus on using a technique known as RNA interference to shut down expression of the disease causing gene:

RNA interference in the HD mouse and non-human primate striatum to improve motor and cognitive symptoms (direct brain injection)
RNA interference in the HD mouse cortex to improve anxiety and depressive symptoms (direct brain injection)
CNS wide delivery of RNA interference in the HD mouse brain (delivery into vasculature or CSF)

Another focus of the McBride Laboratory has been the creation of a non-human primate model of HD, which recapitulates several of the neuropathological changes and behavioral symptoms seen in human HD patients. Currently, the lab is investigating changes in brain connectivity in this new model using diffusion tensor imaging and resting state functional MRI.

The McBride Lab has recently been involved in a large effort at the ONPRC to characterize a new, genetic model of the neurodegenerative disorder, Batten Disease (BD) in the Japanese Macaque Colony. BD affected animals show key genetic, pathological and behavioral manifestations of disease that seen in human children suffering from BD.

The goal with both the HD and BD models will be to use them to better understand disease progression, to develop biomarkers of disease progression and to assess viable therapies that can translate into the clinic to help human patients suffering from these fatal diseases.

Areas of interest

  • Developing therapies for neurodegenerative diseases, including Huntington's and Batten diseases
  • Creating non-human primate models of neurodegenerative diseases
  • Developing and testing novel gene therapy strategies to deliver genes to the brain
  • Assessing brain connectivity in neurodegenerative diseases using novel imaging techniques
  • Translational therapeutics
  • Viral vectors
  • Neurosurgery

Education

  • B.S., University of Illinois 1998
  • Ph.D., Rush University Medical Center 2005
  • Fellowship:

    • Post-doctoral fellowship, Gene Therapy, University of Iowa, 2005-2008
    • Post-doctoral fellowship, Neuroscience, Oregon National Primate Research Center, 2008-2010

Honors and awards

  • 2008 Keynote Address, Huntington’s disease Society of America conference, Chicago, IL
  • 2015 OHSU Technology Transfer and Business Development Award: Top Industry Collaboration
  • 2016 OHSU Technology Transfer and Business Development Award: Recognized Industry Collaboration for 2016

Memberships and associations

  • American Society of Gene and Cell Therapy, member
  • Society for Neuroscience, member
  • Society for Neuroscience, Oregon Chapter, member

Publications

  • Kordower JH, Emborg ME, Bloch J, Shuang M, Chu Y, Leventhal L, McBride JL, Chen E, Palfi S, Roitberg BZ, Brown D, Holden J, Pyzalski R, Taylor MD, Carvey P, Ling ZD, Trono D, Hantraye P, Deglon N, Aebischer P.  Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease.  Science 290(27):767-773, 2000.

  • McBride JL, Ramaswamy S, Bartus R, Gasmi M, Herzog C,  Brandon E, Zhou L, Pitzer MR, Barry-Kravis E, Kordower JH.  Viral delivery of glial cell line-derived neurotrophic factor improves behavior and protects striatal neurons in a mouse model of Huntington's disease.  Proceedings of the National Academy of Sciences 103(24):9345-50, 2006

  • Kumar P, Wu H, McBride JL, Jung KE, Kim MH, Davidson BL, Lee SK, Shankar P, Manjunath N. Transvascular delivery of small interfering RNA to the central nervous system. Nature 5;448 (7149):39-43, 2007

  • McBride JL, Boudreau R, Harper SQ, Staber PD, Mas Monteys A, Martins I, Burstein H, Peluso RW, Polisky B, Carter B and Davidson BL. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi.  Proceedings of the National Academy of Sciences, 105(15) 5868-5873, 2008

  • Boudreau RL, McBride JL, Martins I, Shen S, Xing Y, Carter BJ and Davidson BL.  Non-allele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington’s disease mice. Molecular Therapy, 17(6):1053-63, 2009

  • McBride JL, Pitzer, MR, Boudreau RL, Dufour B, Ojeda SR and Davidson BL. Preclinical Safety of RNAi-Mediated HTT Suppression in the Rhesus Macaque as a Potential Therapy for Huntington's Disease. Molecular Therapy, 19(12): 2152-2162, 2011

  • Dufour BD, Smith C, Clark R, Walker T and McBride, JL.  Intra-jugular vein delivery of AAV9-RNAi prevents neuropathological changes and weight loss in Huntington’s Disease mice, Molecular Therapy, 22(4):797-810, 2014

  • Keiser M, Kordasiewicz H and McBride JL. Gene Silencing Strategies for Dominantly Inherited Neurodegenerative Diseases: lessons from Huntington’s Disease and Spinocerebellar Ataxia. Human Molecular Genetics, 25(r1):53-64, 2016

  • Dufour BD and McBride JL. Corticosterone dysregulation exacerbates disease progression in the R6/2 transgenic mouse model of Huntington’s disease. Experimental Neurology, 283 (Pt A):308-17, 2016

  • McBride JL, Neuringer M, Ferguson B, Renner L, McGill T, Stoddard J, Peterson S, Zweig R, Kohama S, Tagge I, Su W, Sherman L, Domire J, Ducore R, Colgin L and Lewis A. Discovery of  a CLN7 model of Batten Disease in non-human primates, Neurobiology of Disease, 119: 65-78, 2018

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