Tom Maniatis, PhD

Tom Maniatis, PhD

Overview

Academic Appointments

  • Isidore S. Edelman Professor of Biochemistry and Molecular Biophysics

Administrative Titles

  • Director, Columbia University Precision Medicine Initiative
  • Executive Committee, Zukerman Mind Brain Behavior Institute
  • Principal Investigator, Maniatis Lab
  • Scientific Director and Chief Executive Officer of the New York Genome Center

Dr. Maniatis is known for pioneering the development of gene cloning technology and its application to both basic research and biotechnology. He also coauthored the definitive laboratory manual on Molecular Cloning. His research has led to fundamental advances in understanding the mechanisms of gene regulation and RNA splicing, the biochemistry of innate immunity signaling pathways, the function of single cell diversity in the nervous system, and neurodegenerative disease mechanisms. Dr. Maniatis received his B.A. and MS. degrees from the University of Colorado in chemistry and biology, and his Ph.D. in molecular biology from Vanderbilt University. After postdoctoral studies at Harvard University and the Laboratory of Molecular Biology, Cambridge, England, Dr. Maniatis was a professor at the California Institute of Technology and subsequently at Harvard University.

Gender

  • Male

Credentials & Experience

Education & Training

  • BA, 1965 Biology, University of Colorado
  • MS, 1967 Chemistry, University of Colorado
  • PhD, 1971 Molecular Biology, Vanderbilt University

Honors & Awards

Dr. Maniatis’ research has been recognized by many awards, including the Eli Lilly Award in Microbiology and Immunology, The Richard Lounsbery Award for Biology and Medicine (Awarded by the French and U.S National Academy of Sciences), and the 2012 Lasker-Koshland Special Achievement Award in Medical Science.  He is a member of the U.S. National Academy of Science, the U.S. Academy of Medicine, and a fellow of the U.S. Academy of Arts and Sciences.

Research

The primary focus of my lab during the past 10 years has been in two areas: 1. Disease mechanisms of ALS, which involves a combination of human genetic, stem cell and animal model approaches, and 2. The structure and function of the clustered protocadherin (Pcdh) genes.  We have used behavioral assays in both projects to characterize the phenotypic consequences of mutations in mouse models.  The ALS animal model work has involved the use of various neuromuscular behavioral studies of the SOD1 G93A mouse model, while the protocadherin project has involved studies of both motor function and affective behavior (depression and anxiety).  Manuscripts describing both studies are under review. The most recent ALS work is a study of the role of autophagy in ALS disease progression, and these studies involved various studies of motor function such as the rotarod test for motor coordination and muscle strength.  The protocadherin studies involve various assays for affective function (anxiety and depression), in Pcdha gene cluster deletion mice. We have shown that these mice display a cell-autonomous serotonergic wiring phenotype, and have characterized the behavioral consequences.  Recent human genetic studies from other laboratories have implicated the Pcdh gene cluster in autism and other neurological diseases.  We have generated a series of well-characterized deletion mutants in the Pcdh gene cluster, and are characterizing their behavioral phenotypes. Thus, the behavior core is central to our ongoing and future studies.

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

Grants

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

Sep 1 2017 - May 31 2022

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

TRANSFORMING GROWTH FACTOR BETA SIGNALING IN A MOUSE MODEL OF AMYOTROPHIC LATERAL SCLEROSIS (Federal Gov)

Sep 17 2018 - Aug 31 2020

THE ROLE OF AUTOPHAGY AND THE TBK1 GENE IN ALS (Private)

Sep 15 2017 - Sep 14 2019

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

Aug 1 2016 - Jul 31 2019

COUPLING PROMOTER CHOICE AND ALTERNATIVE RNA (Federal Gov)

Jun 1 2017 - May 31 2019

AUTOPHAGY IN ALS (Private)

Jan 5 2017 - Jan 1 2019

A STRATEGY FOR MAPPING THE HUMAN SPINAL CORD WITH SINGLE CELL RESOLUTION (Private)

Sep 1 2017 - Aug 31 2018

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

Selected Publications