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KLANN LABORATORY

KLANN LABORATORY

About

We are a molecular neuroscience laboratory whose research is focused on understanding the molecular mechanisms of memory and how these mechanisms are disrupted in a variety of cognitive disorders.

Eric Klann, Ph.D

Professor and Director of Center for Neural Science, New York University

Center for Neural Science

CNS is the focus for teaching and research in the brain sciences at NYU’s Washington Square Campus.

Klann Projects

Our research is focused on the molecular mechanisms of translational control in the brain, how they are involved in activity-dependent, long-lasting changes in neuronal function, whether these mechanisms are required for complex behaviors such as memory, and whether they are disrupted in neurodevelopmental disorders and neurodegenerative disease.

We use a number of experimental approaches to gain a greater understanding of translational control mechanisms necessary for maintaining long-lasting changes in synaptic strength and memory. Detailed biochemical and sophisticated imaging experiments are employed to delineate the molecular signaling cascades that couple receptors to the translational apparatus during long-lasting synaptic plasticity in the hippocampus, amygdala, cortex, and striatum, and whether these types of translational control are required for memory formation, social behaviors, and behavioral flexibility.

We also conduct electrophysiological, biochemical, imaging, antd behavioral studies with various knockout and transgenic mice to determine how precise genetic manipulations that either activate or abolish specific translational control mechanisms alter synaptic function and behavior. We also study how molecular signaling, translational control, synaptic plasticity, and behavior are altered in mouse models of developmental disability, autism, aging, and Alzheimer’s disease. We develop novel technologies to identify newly synthesized proteins in response to extracellular stimuli and in disease models in neurons, brain slices, and peripheral tissues.

Finally, we generate new tools and mouse models to study the role of de novo protein synthesis in normal brain function and in pathophysiology associated with neurodevelopmental and neurodegenerative disease.

TRANSLATIONAL CONTROL OF LEARNING & MEMORY​

Mechanisms of translational control in synaptic plasticity and cognitive function

It has been known for many years that long-lasting forms of synaptic plasticity and long-term memory require new protein synthesis. However, until the early 2000s, little was known concerning the signaling pathways required to couple activation of various neurotransmitter receptors to the translation machinery during these processes. Our laboratory has spent many years delineating the translational control pathways that regulate eIF4E- and eIF2-dependent translation initiation during LTP, LTD, and memory formation in the hippocampus. More recently, we have focused our efforts on understanding the cell type specificity of eIF4E- and eIF2-dependent translation in the amygdala during auditory threat memory using novel conditional and inducible protein synthesis inhibitor (ciPSI) mouse lines and viruses that we have developed.

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Selected important publications since 2008:

Hoeffer, C.A., Tang, W., Wong, H., Santillan, A., Patterson, R.J., Martinez, L.A., Tejada-Simon, M.V., Paylor, R., Hamilton, S.L., and Klann, E. (2008) Removal of FKBP12 enhances mTOR/Raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron 60: 832-845. PMCID: PMC2630531 PubMed Link

Huynh, T., Santini, E., Mojica, E., Fink, A.E., Hall, B.S., Fetcho, R.N., Grosenick, L., Deisseroth, K., LeDoux, J.E., Liston, C., and Klann, E. (2018) Activation of a novel p70 S6 kinase 1-dependent signaling cascade in the basal nucleus of the amygdala is required for the acquisition of extinction memory. Mol. Psychiatry 23: 1394-1401. PMCID: PMC5668214 PubMed Link

Shrestha, P., Ayata, P., Herrero-Vidal, P., Longo, F., Gastone, A., LeDoux, J.E., Heintz, N., and Klann, E. (2020) A cell type-specific drug-inducible protein synthesis inhibition in mice mouse elucidates the requirement for rapid neuronal translation in memory consolidation. Nat. Neurosci23: 281-292. PMCID: PMC7147976 Pubmed Link

Shrestha, P., Shan, Z., Marmarcz, M. Ruiz, K.S.A., Zerihoun, A.T., Juan, C.-Y., Herrero-Vidal, P.M., Pelletier, J., Heintz, N., and Klann, E. (2020) Amygdala inhibitory neurons as loci for translational control of emotional memories. Nature 586: 407-411. PMCID: PMC7572709 PubMed Link

FRAGILE X SYNDROME​

Cellular and molecular basis of synaptic dysfunction and aberrant behavior in FXS

For the last fifteen years we have been determining the molecular basis for dysregulated protein synthesis in fragile X syndrome (FXS) and how altered translation contributes to altered synaptic plasticity aberrant behavior in FXS model mice. We recently have extended our studies on altered translational control in FXS to studies of human tissues and cells.

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Selected important publications since 2006:

Hou, L., Antion, M.D., Hu, D., Spencer, C.M., Paylor, R.E., and Klann, E. (2006) Dynamic translational and proteasomal regulation of the fragile X mental retardation protein controls metabotropic glutamate receptor-dependent long-term depression. Neuron 51: 441-454.  PMID: 16908410 PubMed Link

Bhattacharya, A., Kaphzan, H., Alvarez-Dieppa, A.C., Murphy, J.P., Pierre, P., and Klann, E. (2012) Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron 76: 325-337. PMCID: PMC3479445 PubMed Link

Bhattacharya, A., Mamcarz, M., Mullins, C., Choudhury, A., Boyle, R.G., Smith, D.G., Walker, D.W., and Klann, E. (2016) Targeting translation control with p70 S6 kinase 1 inhibitors to reverse phenotypes in fragile x syndrome mice. Neuropsychopharmacology 41: 1991-2000. PMCID: PMC4908636 PubMed Link 

Santini, E., Huynh, T.N., Longo, F., Koo, S.Y., Mojica, E., D’Andrea, L., Bagni, C., and Klann, E. (2017) Reducing eIF4E-eIF4G interactions restores the balance between protein synthesis and actin dynamics in fragile X syndrome model mice. Sci. Signal., 10: eaan0665. PMCID: PMC5858943 PubMed Link

NEURODEGENERATIVE DISEASE

Cellular and molecular basis of synaptic failure and memory impairments in aging and AD

Although many years ago we found that reactive oxygen species (ROS) are required for full expression of hippocampal LTP and memory, it is clear that the aged and diseased brain handle ROS much differently as many studies have pointed to a role for excessive ROS and oxidative stress in age-related cognitive decline and impaired memory associated with Alzheimer’s disease (AD). We have studied the role of ROS in aging-related impairments in LTP and memory that are associated with normal aging, and have conducted studies to that ROS derived from mitochondria are responsible for oxidative stress-induced impairments in synaptic plasticity and memory in mice that model AD. In addition, we have identified signaling pathways that are activated as part of the integrated stress response (ISR) in response to soluble amyloid-beta and in AD model mice. Notably, we have found that prolonged activation of these pathways results in altered translational control, which contributes to synaptic dysfunction and memory deficits in AD model mice.

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Selected important publications since 2009:

Ma, T., Hoeffer, C.A., Wong, H., Massaad, C.A., Zhou, P., Iadecola, C., Murphy, M.P., Pautler, R.G., and Klann, E. (2011) Amyloid b-induced impairments in hippocampal synaptic plasticity are rescued by decreasing mitochondrial superoxide. J. Neurosci31: 5589-5595. PMCID: PMC3095121 PubMed Link

Ma, T., Trinh, M.A., Wexler, A.J., Bourbon, C., Gatti, E., Pierre, P., Cavener, D.R., and Klann, E. (2013) Suppression of eIF2a kinases alleviates Alzheimer’s disease-related plasticity and memory deficits. Nat. Neurosci16: 1299-1305. PMCID: PMC3756900 PubMed Link

Ma, T., Chen, Y., Vingtdeux, V., Zhao, H., Viollet, B., Marambaud, P., and Klann, E. (2014) Inhibition of AMP-activated protein kinase signaling alleviates impairments in hippocampal synaptic plasticity induced by amyloid b. J. Neurosci. 34: 12230-12238. PMCID: PMC4152616 PubMed Link

Oliveira, M.M., Lourenco, M.V., Longo, F., Kasica, N., Yang, W., Ureta, G., Medonca, P.H.J., Bernales, S., Ma, T., De Felice, F.G., Klann, E.*, and Ferreira, S.T.* (2021) Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity and memory in mouse models of Alzheimer’s disease. Sci. Signal. 14: eabc5429. *equal contribution. PMCID: in progress.

Use of ‘omics to Identify Translating mRNAs and Newly Synthesized Proteins in Memory and Disease

Development of techniques to identify translating mRNAs and newly synthesized proteins in the nervous system

We have used translational ribosome affinity profiling (TRAP) and ribosome profiling to identify mRNA being translated during memory formation and mRNAs that are being translated inappropriately in disease models. In addition, we have developed new techniques utilizing surface sensing of translation (SUnSET) and bioorthogonal noncanonical amino acid tagging (BONCAT) coupled with stable isotope labeling by amino acid in cell culture (SILAC) to selectively isolate and quantify de novo proteins synthesized within a specified temporal window. We have used this approach to determine the identity alterations in newly synthesized proteins in striatal neurons treated with antipsychotics, and in adult brain slices from fragile X syndrome and Alzheimer’s disease model mice.

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Selected important publications since 2014:

Bowling, H., Zhang, G., Bhattacharya, A., Perez-Cuesta, L.M., Deinhardt, K., Hoeffer, C.A., Neubert, T.A., Gan, W.-B., Klann, E.*, and Chao, M.V.* (2014) Antipsychotics enhance neuronal morphological complexity via mTORC1-dependent translation. Sci. Signal. 7: ra4. *equal contribution. PMCID: PMC4063438 PubMed Link

Bowling, H., Bhattacharya, A., Zhang, G., Alam, D., Lebowitz, J.Z., Aryal, S., Bohm-       Levine, N., Lin, D., Singha, P., Puckett, R., Zhou, L., Sharp, K., Kirshenbaum, K., Berry-Kravis, E., Neubert, T.A., and Klann, E. (2019) Altered steady state and activity-dependent de novo protein expression in fragile X syndrome. Nat. Commun. 10: 1710. PMCID: PMC6461708 PubMed Link

Ostroff, L.E., Santini, E., Sears, R., LeDoux, J.E., Lhakhang, T., Tsingos, A., Heguy, A., and Klann, E. (2019) Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amygdala. eLife 8: e51607. PMCID: PMC6924958 PubMed Link

Aryal, S., Longo, F. and Klann, E. (2021) Genetic removal of p70 S6K1 corrects coding sequence length dependent alterations in mRNA translation in fragile X syndrome mice. Proc. Natl. Acad. Sci. USA 118: e2001681118. PMCID: PMC8106352  PubMed Link

Elder, M.K., Erdjument-Bromage, H., Oliveira, M.M., Mamcarz, M., Neubert, T.A., and, Klann, E. (2020) Dysregulation of the de novo proteome accompanies pathology progression in the APP/PS1 mouse model of Alzheimer’s disease. Commun. Biol. 4: 823. PMCID: in progress.

Meet the Members

Eric Klann is Professor and Director of the Center for Neural Science at New York University. Dr. Klann received his Ph.D. from Virginia Commonwealth Univeristy School of Medicine in 1989, did postdoctoral training at Baylor College of Medicine with Dr. David Sweatt, and previously held faculty positions at the University of Pittsburgh and Baylor College of Medicine. Dr. Klann’s research is focused on the molecular mechanisms of translational control and their role in activity-dependent changes in synaptic function and behavior, including cognition. He also studies how dysregulated translational control contributes to altered synaptic function and aberrant behaviors in developmental brain disorders and neurodegenerative disease. Dr. Klann has published over 160 original research articles, reviews, commentaries, and book chapters. More on Dr.Klann

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Eric Klann
Principle Investigator
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Maggie Donohue
Senior Research Associate
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Mauricio Oliveira
Post-Doctoral Fellow
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Muhaned Mohamed
MD/PhD student
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Prerana Shrestha
Visiting Faculty
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Ela Golhan
Lab Manager
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Jessica Alapin
Post-Doctoral Fellow
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Drew Adler
MD/PhD student
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Harrison Evans
Post-Doctoral Fellow
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Vaish Shankar
Post-Doctoral Fellow
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Wendy Liu
Ph.D Student
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Keylin Banegas-Morales
Undergraduate Student
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Nishika Navrange
Undergraduate Student
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Emily Lu
Undergraduate Student
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Astra Yu
Undergraduate Student
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Carson Schultz
Undergraduate Student
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Eric KlannIlene Tisnovsky
Undergraduate Student

Lab Alumni

Eric Klann

Professor & Director, Center for Neural Science, NYU
Principle Investigator
Ph.D. Commonwealth University B.S Gannon University

Eric Klann is Professor and Director of the Center for Neural Science at New York University. Dr. Klann received his Ph.D. from Virginia Commonwealth University School of Medicine in 1989, did postdoctoral training at Baylor College of Medicine with Dr. David Sweatt, and previously held faculty positions at the University of Pittsburgh and Baylor College of Medicine. Dr. Klann’s research is focused on the molecular mechanisms of translational control and their role in activity-dependent changes in synaptic function and behavior, including cognition. He also studies how dysregulated translational control contributes to altered synaptic function and aberrant behaviors in developmental brain disorders and neurodegenerative disease. Dr. Klann has published over 160 original research articles, reviews, commentaries, and book chapters. Dr. Klann serves as a Reviewing Editor for the Journal of Neuroscience, a Section Editor for Brain Research, and serves on the editorial boards of several other journals. He is a former member and chair of the Neural Oxidative Metabolism & Death and Molecular & Cellular Substrates of Complex Disorders Study Sections of the National Institutes of Health. Dr. Klann serves on the Scientific Advisory Boards for the Pitt Hopkins Syndrome Foundation and the Foundation for Angelman Syndrome Therapeutics, where he is also the Chair. He also has served on the Fragile X Outcomes Measures and TSC Neurocognitive Working Groups for the National Institutes of Health. Dr. Klann has served as the Treasurer and the President of the Molecular and Cellular Cognition Society. He is the recipient of a NARSAD Distinguished Investigator Award and the Jacob Javits Neuroscience Investigator Award from the National Institutes of Neurological Disorders and Stroke, and is a Fellow of the American Association for the Advancement of Science.

Education and Training
  • 1980-1984
    B.S. Chemistry, Gannon University, Erie, PA

  • 1984-1989

    Ph.D. Biochemistry and Molecular Biophysics
    Medical College of Vriginia/Virginia Commonwealth University, Richmond, VA

  • 1989-1994

    Postdoctoral fellow
    Department of Neuroscience
    Baylor College of Medicine, Houston, TX

Positions
  • 1994 – 2000

    Assistant Professor, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA

  • 2000 – 2001

    Associate Professor, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA

  • 2001 – 2005

    Associate Professor & Director of Graduate Studies, Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX

  • 2005 – 2006

    Professor, Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX

  • 2006 – 2016

    Professor, Center for Neural Science, New York University, New York, NY

  • 2012 – 2013

    Visiting Scientist, Shonan Research Center, Takeda Pharmaceuticals, Fujisawa, Japan

  • 2016 – present

    Professor and Director, Center for Neural Science, New York University, New York, NY

Honors and Awards
  • 1989

    National Institute of Mental Health Training Grant

  • 1989-1991

    American Society for Neurochemistry Young Investigator Travel Award

  • 1991-1993

    National Institutes of Health National Research Service Award

  • 1993

    American Society for Neurochemistry Young Investigator Travel Award

  • 1993-1994

    National Institutes of Health National Research Service Award

  • 1995-2000

    National Institutes of Health First Award

  • 1998-1999

    Co-President, Pittsburgh Chapter of Society for Neuroscience

  • 1999

    Austria Ministry of Science Young Investigator Travel Award

  • 1997-2000

    Review Panel Member, Protective Agents in Neural Cell Dysfunction, U.S. Army Medical Research and Materiel Command

  • 2001

    International Society for Neurochemistry Young Investigator Award

  • 2003-2004

    Cynthia and George Mitchell Dementia Research Award

  • 2004

    Basic Health Sciences Outstanding Alumnus Award, Medical College of Virginia, Virginia Commonwealth University

  • 2008-2009

    Chair, Neural Oxidative Metabolism and Death Study Section (NOMD), National Institutes of Health

  • 2009

    Morosky College of Health Professions and Sciences Distinguished Alumni Award, Gannon University

  • 2010 – 2012

    College of CSR Reviewers, National Institutes of Health

  • 2012 – 2015

    President, Molecular and Cellular Cognition Society

  • 2013

    Brain & Behavior Foundation NARSAD Distinguished Investigator Award

  • 2013

    Fellow, American Association Fro the Advancement of Science

  • 2014

    Javits Neuroscience Investigator Award, National Institute of Neurological Disorders and Stroke

  • 2017

    Butler High School (Pennsylvania) Distinguished Graduate Award

Eric Klann speaks at Brain Awareness
June 4, 2021
U. of Chicago Brain Awareness Day (2012)