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John H. Weiss

Professor, Neurology
School of Medicine

Professor, Anatomy & Neurobiology
School of Medicine

PH.D., Stanford University, 1991


M.D., Stanford University, 1983

Phone: (949) 824-6774, 8479
Fax: (949) 824-1668
Email: jweiss@uci.edu

University of California, Irvine
Gillespie Neuroscience Research Facility
Mail Code: 4292
Irvine, CA 92697


Research
Interests
Cell culture, selective neurodegeneration, cell death,excitotoxicity, glutamate, AMPA, kainate, NMDA, calcium,zinc, Alzheimer's, ALS, basal forebrain, motor neurons, freeradicals, trophic factors, LTP, synaptic plasticity
   
URLs www.ucihs.uci.edu/anatomy/weiss.html
   
neurobiology.uci.edu/frames/fp_frameset.html
   
Academic
Distinctions
Stanford Medical Alumni Scholars Program, 1980-1981; March of Dimes Medical Student Research Fellowship, 1980-1981; American Academy of Neurology Research Fellowship in Neuropharmacology, 1987-1990; Dana Fellow in Neuroscience, Stanford University, 1990-1991; Clinician Investigator Award, National Institute on Aging, NIH, 1990-1995; PEW Scholar in the Biomedical Sciences, 1991-1996; Independent Scientist Award, National Institute on Aging, 1998-2003
   
Appointments Molecular Biology, Genetics and Biochemistry (MBGB)
Neuroscience Interdepartmental Graduate Program
   
Research
Abstract
A key focus of Dr. Weiss and his collaborators is to elucidate factors and mechanisms that contribute to disease associated degeneration of neurons in the central nervous system and to identify potential new approaches to decreasing that injury. Currently, research into mechanisms of neurodegeneration is one of the hottest and most productive areas of neuroscience due to the far-reaching implications for understanding pathogenesis of, and establishing effective treatments for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and epilepsy.

Dr. Weiss' research has provided groundbreaking insights into a critical and previously little-explored issue: what are the factors that make certain subsets of central neurons especially vulnerable to degeneration in these conditions? Early studies led him to propose a specific and novel hypothesis that activation of AMPA/kainate types of glutamate receptors may play previously unappreciated roles. Other studies focused on ways in which the endogenous cation, Zn2+, may contribute to neurodegeneration. Specific factors that are being examined include the presence of unusual Ca2+ and Zn2+ permeable AMPA channels on certain neurons, intracellular homeostasis of these ions and ways in which these ions can each induce deleterious effects on mitochondria.

Other ongoing studies in the Weiss laboratory make use of disease models to examine ways in which these mechanisms contribute to injury, and for testing new therapeutic interventions.
   
Publications Weiss, J.H., Pike, C.J. and Cotman, C.W. Ca2+ channel blockers attenuate ß-amyloid peptide toxicity to cortical neurons in culture, J. Neurochem. 62, 372-375 (1994).
   
  Yin, H., Turetsky, D., Choi, D.W. and Weiss, J.H., Cortical neurons with Ca2+ permeable AMPA/kainate channels display distinct receptor immunoreactivity and are GABAergic, Neurobiol. Dis. 1, 43-49 (1994).
   
  Carriedo, S. G., Yin, H. Z., and Weiss, J. H., Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. J. Neurosci. 16, 4069-4079 (1996).
   
  Carriedo, S. G., Yin, H. Z.,Sensi, S.L. and Weiss, J. H., Rapid Ca2+ entry through Ca2+-permeable AMPA/kainate channels triggers marked intracellular Ca2+ rises and consequent oxygen radical production. J. Neurosci. 18, 7727-7738 (1998).
   
  Sensi, S.L., Yin, H.Z., Carriedo, S.G., Rao, SS and Weiss, J.H.
Preferential Zn2+ influx through Ca2+ permeable AMPA/kainate channels
triggers prolonged mitochondrial superoxide production. Proc. Natl. Acad. Sci. (USA) 96, 2414-2419 (1999).
   
  Yin, H.Z., Sensi, S.L., Carriedo, S.G., and Weiss, J.H. Dendritic localization of Ca2+ permeable AMPA/kainate channels in hippocampal pyramidal neurons. J. Comp. Neurol. 409, 250-260 (1999).
   
  Carriedo, S.G., Sensi, S.L., Yin, H.Z. and Weiss, J.H. AMPA exposures induce mitochondrial Ca2+ overload and ROS generation in spinal motor neurons in vitro. J. Neurosci. 20, 240-250 (2000).
   
  Weiss, J.H. and Sensi, S.S. Ca2+ - Zn2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration. Trends Neurosci. 23, 365-371 (2000).
   
  Weiss, J.H. and Sensi, S.S. and Koh, J.Y. Zn2+ : A novel ionic mediator of neural injury in brain disease. Trends Pharmacol. Sci. 21, 395-401 (2000).
   
  Jiang, D., Sullivan, P.G., Sensi, S.L., Steward, O. and Weiss, J.H. Zn2+ induces permeability transition pore opening and release of pro-apoptotic peptides from neuronal mitochondria. J. Biol. Chem. 276, 47524-47529 (2001).
   
  Yin, H.Z., Sensi, S.L., Ogoshi, F. and Weiss, J.H. Blockade of Ca2+ permeable AMPA/kainate channels decreases oxygen glucose deprivation induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal neurons. J. Neurosci. 22, 1273-9 (2002).
   
  Jia, Y.S., Jeng, J.M., Sensi, S.L. and Weiss, J.H. Zn2+ currents are mediated by Ca2+ -permeable AMPA/kainate channels in cultured hippocampal neurons, J. Physiol. 543.1, 35048 (2002).
   
  Rao, S.D., Yin, H.Z. and Weiss, J.H. Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons, J. Neurosci. 23, 2627-2633 (2003).
   
  Sensi, S.L., Ton-That, D., Sullivan, P.G., Jonas, E.A., Gee, K.R., Kaczmarek, L.K. and Weiss, J.H. Modulation of mitochondrial function by endogenous Zn2+ pools, Proc. Natl. Acad. Sci. (USA) 100, 6157-6162 (2003).
   
  Rao, S.D. & Weiss, J.H. Excitotoxic and oxidative cross-talk between motor neurons and glia in ALS pathogenesis. Trends Neurosci. 27 (1) 17-23 (2004).
   
  Ogoshi, F. & Weiss, J.H. Heterogeneity of Ca2+ -permeable AMPA/kainate channel expression in hippocampal pyramidal neurons: Fluorescence imaging and immunocytochemical assessment. J. Neurosci. 23(33): 10521-30 (2003).
   
  Ogoshi, F. Yin, H.Z., Kuppumbatti, Y., Song, B, Amindari, S., Weiss, J.H. Tumor-necrosis-factor-alpha (TNF-?) induces rapid insertion of Ca2+-permeable ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neurons. Exp. Neurol. 193, 384-393 (2005).
   
  Weiss, J. H., Kwak, S., Ca2+ permeable AMPA channels in neurodegenerative disease and ischemia, Curr. Op. Neurobiol. 16(3):281-7. (2006).
   
  Rao, S.D., Banack, S.A., Cox, P.A. and Weiss, J.H. BMAA selectively injures motor neurons via AMPA/kainate receptor activation. Exp Neurol. 201: 244-252 (2006).
   
  Yin, H.Z., Tang, D.T., and Weiss, J.H. Intrathecal infusion of a Ca2+ permeable AMPA channel blocker slows loss of both motor neurons and of the astrocyte glutamate transporter, GLT-1 in a mutant SOD1 rat model of ALS. Exp Neurol. 207(2):177-85 (2007). (PMID: 17719032)
   
  Richichi, C., Brewster, A.L., Bender, R.A., Simeone, T.A., Zha, Q, Yin, H.Z., Weiss, J.H. and Baram, T.Z. Mechanisms of seizure-induced 'transcriptional channelopathy' of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Neurobiol. Dis. 29(2):297-305 (2008).
   
  Dietz, R.M., Weiss, J. H. and Shuttleworth, C.W. Zn2+ Influx is Critical for Some Forms of Spreading Depression in Brain Slices. J. Neurosci. 28(32):8014-24(2008).
   
  Medvedeva , Y.V., Lin, B., Shuttleworth, C.W. and Weiss, J. H. Intracellular Zn2+ accumulation contributes to synaptic failure, mitochondrial depolarization and cell death in an acute slice oxygen glucose deprivation (OGD) model of ischemia. J. Neurosci. 29(4):1105-14 (2009).
   
  Shuttleworth, C.W. and Weiss, J.H. Zinc: New clues to diverse roles in brain ischemia. Trends Pharmacol. Sci. (2011) 32(8):480-6.
   
Professional
Societies
Society for Neuroscience
Americal Academy of Neurology
American Neurological Association
American Association for the Advancement of Science
American Epilepsy Society
European Neurological Association
Society for Neuroscience
New York Academy Of Sciences
   
Graduate Programs Neurobiology

Interdepartmental Neuroscience Program

Cellular and Molecular Biosciences

   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=2419
   
Last updated 10/31/2011