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Tom Maniatis, PhD

Academic Appointments

  • Isidore S. Edelman Professor of Biochemistry and Molecular Biophysics

Current Administrative Positions

  • Chair, Biochemistry & Molecular Biophysics
  • Director, Columbia University Precision Medicine Initiative
  • Executive Committee, Zukerman Mind Brain Behavior Institute
  • Member, Board of Directors, The New York Genome Center
Tom Maniatis, PhD

Our laboratory is interested in understanding fundamental mechanisms of transcription and RNA splicing in the nervous system, and how these mechanisms bear on neuronal connectivity and neurodegenerative diseases. Interest in neuronal connectivity arose from our discovery of a remarkable organization of a large cluster of genes encoding cell surface cadherin-like proteins called protocadherins.This unusual gene organization leads to the generation of enormous individual cell surface diversity at the synapse through a mechanism that involves stochastic promoter choice and alternative RNA splicing. We are studying the detailed mechanisms of promoter choice, and are investigating the function of the clustered protocadherins in mice.

We are also using embryonic stem cell differentiation and deep sequencing methods to study transcription, RNA splicing, protein-RNA interactions, in ALS disease models. This involves studies of SOD1, FUS and TDP43 mouse models, and human patient derived iPS cells.Our current focus is in understanding the role of neuroinflammation in ALS disease mechanisms, specifically the role of innate immunity and autophagy. Our interest in neuroinflammation arose from our earlier studies of the signaling pathways involved innate immunity, and more recent studies of autophagy. Several years ago we discovered the role of the kinase TBK-1 in innate immunity, and recent studies have implicated TBK-1 in both sporadic and familial ALS. TBK-1 activity lies at the interface of innate immunity and autophagy both of which have been implicated in ALS disease mechanisms.

Departmental Appointments

  • Department of Biochemistry and Molecular Biophysics

Centers/Institutes/Programs

Lab Locations

  • Hammer Health Sciences Building

    701 West 168th Street
    Room 601
    New York, NY 10032
    Phone:
    (212) 305-3669
    Email:
    tm2472@cumc.columbia.edu

Research Interests

  • Regulation of RNA Transcription and Splicing
  • The Role of Neuroinflammation in ALS
  • Neurobiology of Disease
  • Synapses and Circuits
  • Stem Cell Biology
  • ALS Disease Mechanisms
  • Genetic Basis of Neurological Diseases

NIH Grants

  • ROLE OF THE PROTOCADHERIN ALPHA GENE CLUSTER IN SEROTONERGIC CIRCUITRY FORMATION AND ITS IMPLICATIONS IN DEPRESSIVE DISORDERS (Federal Gov)

    Jan 15 2016 - Nov 30 2020

    SINGLE CELL STUDIES OF TDP-43 MUTATIONS ON ALS DISEASE PROGRESSION (Private)

    Aug 1 2016 - Jul 31 2019

    AUTOPHAGY IN ALS (Private)

    Jan 5 2017 - Jan 1 2019

    THE ROLE OF AUTOPHAGY AND INNATE IMMUNITY IN ALS DISEASE PROGRESSION (Private)

    Sep 1 2015 - Aug 31 2017

    FUNCTIONAL SEGREGATION OF TASTE RESPONSIVE NEURONS (Private)

    Jul 1 2014 - Jun 30 2017

    MECHANISMS OF PROTOCADHERIN PRE-MRNA SPLICING IN THE MAMMALIAN BRAIN (Private)

    Jun 1 2014 - May 31 2017

    THE STRUCTURAL BASIS OF CIS AND TRANS PROTOCADHERIN INTERACTIONS (Federal Gov)

    Sep 1 2013 - May 31 2017

    UNDERSTANDING ALS DISEASE MECHANISMS USING HUMAN TDP-43 IPS-DERIVED MOTOR NEURONS (Private)

    Aug 1 2013 - Jul 31 2016

    ROLE OF P62 IN AMYOTROPHIC LATERAL SCLEROSIS (Federal Gov)

    Jul 1 2014 - Jun 30 2016

    SINGLE CELL STUDIES OF LINEAGE SPECIFIC EXPRESSION OF THE PROTOCADHERIN GENE CLUSTER (Federal Gov)

    Jul 1 2014 - Jun 30 2016

    A COMPARATIVE SINGLE CELL STUDY OF INDUCED PLURIPOTENT AND EMBRYONIC STEM CELL DERIVED MOTOR NEURONS (Private)

    May 1 2014 - Apr 30 2016

    EFFECT OF ALS-CAUSING MUTATIONS ON BINDING OF TDP43 AND FUS TO RNA IN IMNS (Federal Gov)

    Jul 1 2013 - Jun 30 2015

    COMPUTATIONAL ANALYSIS OF GENE EXPRESSION AND ALTERNATIVE RNA PROCESSING IN ALS (Private)

    Jul 1 2012 - Jun 30 2015

    MOLECULAR DISSECTION OF ASTROCYTE TOXICITY IN AMYOTROPHIC LATERAL SCLEROSIS (ALS) (Private)

    Jun 1 2013 - May 31 2014

    DRUG ENHANCEMENT OF MOTOR NEURON VIABILITY (Private)

    Jan 1 2010 - Dec 31 2013

    INVESTIGATION OF A POSSIBLE ROLE OF THE PROTOCADHERIN GENE CLUSTER IN AUTISM (Private)

    Oct 1 2012 - Sep 30 2013

    PROTOCADHERIN GENE EXPRESSION AND FUNCTION (Federal Gov)

    Apr 1 1981 - Sep 29 2013

    THE ROLE OF FUS/TLS IN THE REGULATION OF GENE EXPRESSION (Private)

    Aug 31 2011 - Aug 30 2013

    USE OF INDUCED PLURIPOTENT STEM CELLS TO STUDY MECHANISMS OF FAMILIAL AND SPORADIC ALS (Federal Gov)

    Sep 30 2008 - Jul 31 2013

    COMPUTATIONAL DISSECTION OF MOTOR NEURON-GLIA INTERACTIONS I N ALS (Private)

    Jul 1 2012 - Jun 30 2013

    MODELLING MOTOR NEURONE DISEASE USING INDUCED PLURIPOTENTIAL STEM CELLS (Private)

    Jun 1 2010 - May 31 2013

    GENERATION AND CHARACTERIZATION OF AMYOTROPHIC LATERIAL SCLE ROSIS IPS CELLS (Federal Gov)

    Sep 30 2009 - Aug 31 2012

    USING HUMAN EMBRYONIC STEM (ES) CELLS AND IPS CELLS TO INVES TIGATE FAMILIAL AND SPORADIC ALS DISEASE MECHANISMS (Private)

    Apr 1 2010 - Mar 31 2011

    BLOCKADE OF INTEGRIN-MEDIATED PNS INFLAMMATION IN ALS (Private)

    Jan 1 2010 - Dec 31 2010

Lab Projects

  • ALS Disease Mechanisms
  • Development of Neural Circuits
  • Protocadherin gene expression and function

Lab Members

  • Daniele Canzio, PhD, Postdoctoral Fellow
  • Monica Carrasco, PhD, Associate Research Scientist
  • Weisheng Chen, PhD, Associate Research Scientist
  • Maxime Chevee, Tech B
  • Jackie de Vegvar, Tech B
  • aolo Guarnieri, MD, Associate Research Scientist
  • Elena Kandror, BA, Graduate Student
  • Tom Roberts, BS, Tech B
  • Noam Rudnick, BS, MD/PhD Student
  • Helaina Skop, BS, Graduate Student
  • Tenzin, Lab Member
  • Chan Aye Thu, PhD, Postdoctoral Fellow
  • Andrew Williams, PhD, Postdoctoral Fellow
  • Junqiang Ye, PhD, Research Associate
  • Jin Zhang, PhD, Postdoctoral Fellow
  • Amy Kirner, BS, Tech B
  • Jennifer Liao, BA, Tech B
  • Tom Maniatis, PhD, Chairman
  • George Mountoufaris, BSc, Graduate Student
  • Chiamake Nwakeze, BA, Tech B
  • Sean O'Keeffe, BSc, Computational Biologist
  • Hemali Phatnani, PhD, Associate Research Scientist
  • Gloria Recio, Technician Assistant

Collaborators

Richard Axel - Role of protocadherins in olfactory receptor neuron wiring

Tom Jessell - Astrocyte/motor neuron interactions in ALS

Charles Zuker - single cell analysis of taste receptors

Publications

Publications List