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
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
Molecular Biology, Genetics and Biochemistry (MBGB)
Neuroscience Interdepartmental Graduate Program
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.
The Christopher J. Frederickson Prize for Excellence in Research in the field of Zinc Biology, awarded by the International Society for Zinc in Biology (ISZB) on 9/15/14
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.
Yin, H.Z., Weiss, J.H., Marked synergism between mutant SOD1 and glutamate transport inhibition in the induction of motor neuronal degeneration in spinal cord slice cultures, Brain Res. 1448:153-62 (2012).
Yin, H.Z., Nalbandian. A., Hsu, C.I., Li, S., Llewellyn, K.J., Mozaffar, T., Kimonis, V.E. and Weiss, J.H. Slow Development of ALS-Like Spinal Cord Pathology in Mutant Valosin-Containing Protein (VCP) Gene Knock-in Mice. Cell Death & Disease 3, e374; doi:10.1038/cddis.2012.115 (2012) (PMID: 22898872).
Yin, H.Z., Hsu, C.I., Yu, S., Rao, S.D., Sorkin, L.S., and Weiss, J.H. TNF-a triggers rapid membrane insertion of Ca2+ permeable AMPA receptors into adult motor neurons and enhances their susceptibility to slow excitotoxic injury, Experimental Neurology, 238(2):93-102 (2012).
Clausen, A., McClanahan, T., Ji, S.G. and Weiss, J.H. Mechanisms of Rapid Reactive Oxygen Species Generation in response to Cytosolic Ca2+ or Zn2+ Loads in Cortical Neurons. PLoS One 8(12): e83347 (2013); doi: 10.1371/journal.pone.0083347 (PMID: 24340096; PMCID: PMC3858366)
Medvedeva , Y.V. and Weiss, J. H. Intramitochondrial Zn2+ accumulation via the Ca2+ uniporter contributes to acute ischemic neurodegeneration. Neurobiol. Dis. 68: 137-144 (2014).
Yin, H.Z., Yu, S., Hsu, C.I., Liu, J., Acab, A., Wu, R., Tao, A., Chiang, B.J. and Weiss, J.H. Prolonged intrathecal infusion of the neurotoxic amino acid, BMAA, in rats reproduces characteristic pathological features of ALS. Experimental Neurology 261:1-9 (2014). (PMID: 24918341; PMCID: PMC4194249)
Wigerblad, G., Huie, J.R., Yin, HZ, Leinders, M., Pritchard, R.A., Koehrn F.J., Xuao, W.-H., Bennett, G.J., Huganir R.L., Ferguson, A.R., Weiss J. H., Svensson, C.I. and Sorkin, L.S. Inflammation-induced GluA1 trafficking and membrane insertion of Ca2+ permeable AMPA receptors in dorsal horn neurons is dependent on spinal tumor necrosis factor, PI3 kinase and protein kinase A. Experimental Neurology (2017), 293:144-158. (doi: 10.1016/j.expneurol.2017.04.004; PMID: 28412220).
Medvedeva, Y.V., Ji, S.G., Yin, H.Z. and Weiss, J.H.. Differential vulnerability of CA1 vs CA3 pyramidal neurons after ischemia: possible relationship to sources of Zn2+ accumulation and its entry into and prolonged effects on mitochondria, J. Neurosci. 37(3):726-737 (2017) (DOI: https://doi.org/10.1523/JNEUROSCI.3270-16.2017; PMID: 28100752; PMCID: PMC5242414)
Ji, S.G. and Weiss, J.H. Zn2+-induced disruption of neuronal mitochondrial function: synergism with Ca2+, critical dependence upon cytosolic Zn2+ buffering, and contributions to neuronal injury. Experimental Neurology 302:181-195 (2018) (doi: 10.1016/j.expneurol.2018.01.012; PMID: 29355498; PMCID: PMC5849513).
Ji, S.G., Medvedeva, Y.V., Wang, H.L., Yin, H.Z., and Weiss, J.H. Mitochondrial Zn2+ accumulation: A potential trigger of hippocampal ischemic injury. The Neuroscientist 25(2):126-138 (2019) (published online: May 10, 2018; DOI: 10.1177/1073858418772548; PMID:29742958; PMCID: PMC6730558)
Yin, H.Z., Wang, H.L., Ji, S.G., Medvedeva, Y.V., Tian, G., Bazrafkan, A., Maki, N., Akbari, Y., and Weiss, J.H. Rapid intra-mitochondrial Zn2+ accumulation in CA1 hippocampal pyramidal neurons after transient global ischemia: A possible contributor to mitochondrial disruption and cell death. Journal of Neuropathology and Experimental Neurology, 78(7):655-664 (2019) (DOI: 10.1093/jnen/nlz042; PMID: 31150090; PMCID: PMC6581555)
Ji, S.G., Medvedeva, Y.V., and Weiss, J.H. Zn2+ entry through the mitochondrial calcium uniporter is a critical contributor to mitochondrial dysfunction and neurodegeneration. Experimental Neurology 325:113161 (2020). doi: 10.1016/j.expneurol.2019.113161. PMID:31881218; PMCID: PMC6957126
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
Interdepartmental Neuroscience Program
Cellular and Molecular Biosciences