James E Goldman, MD, PhD

Academic Appointments

  • Professor of Pathology and Cell Biology (in Psychiatry)

Current Administrative Positions

  • Director, Neuropathology Fellowship Program
James E Goldman, MD, PhD

  • 1976-1977 Research Associate, Department of Neurology, Albert Einstein College of Medicine, Bronx, NY
  • 1980 - 1985 Assistant Professor of Pathology, Albert Einstein College of Medicine, Bronx, NY
  • 1985 - 1987 Associate Professor of Pathology, Albert Einstein College of Medicine, Bronx, NY
  • 1987 - 1992 Associate Professor of Pathology (in Psychiatry), Columbia University College of Physicians & Surgeons, NY, NY
  • 1992 - 2015 Professor of Pathology & Cell Biology (in Psychiatry) and Director, Division of Neuropathology, Columbia University College of Physicians & Surgeons, NY, NY
  • 2015 - present Professor of Pathology & Cell Biology (in Psychiatry) and Director, Residency Training in Neuropathology, Columbia University College of Physicians & Surgeons, NY, NY

Our lab is interested in CNS glial cell development, function, and pathology. We study how astrocytes react to the presence of pathological changes and how pathological changes in astrocytes affect the other cells of the CNS.

In collaboration with Osama Al Dalahmah in Pathology and Vilas Menon in Neurology, we are using single nucleus RNASeq, a recent and powerful technique that allows us to explore gene expression of single cells of patients with neurological diseases. We have begun with Huntington disease, an inherited disorder characterized clinically by abnormal, involuntary movements and genetically by an expansion of CAG repeats in the huntingtin gene. We use fresh frozen brain specimens taken from the NY Brain Bank here at the Columbia Medical Center. In comparision to brain tissues of patients without neurological disease, we have found many significant alterations in neurons, glia, and microglia. The studies have also revealed substantial heterogeneity in transcription within individual cell types in both normal and diseased brain tissues. Studies in the near future will query gene expression in single cells in Parkinson disease and in the neurons and glia that surround malignant brain tumors.

In collaboration with Guomei Tang and David Sulzer of Neurology, Guy McKhann, Alexander Sosunov, and Xiaoping Wu of Neurosurgery, and Peter Sims of Systems Biology, we are studying the cellular and molecular changes in astrocytes and neurons that take place during the evolution of epilepsy and in the evolution of autistic-like behavior. Our collaborative group uses mouse models of Tuberous Sclerosis (TS), a disease characterized by seizures and commonly by autism-spectrum disorders, in which cells have constitutively activated mTOR. The mouse model replicates the formation of greatly enlarged neurons that are characteristic of TS and of focal cortical dysplasias. We find that these neurons are highly active and likely represent the cellular substrate of seizures. We also have performed RNASeq and ribosomal profiling and footprinting, which show us that many genes are transcriptionally regulated and also allow us to discover translationally-regulated gene expression.

We continue to study Alexander disease, a degenerative brain disorder caused by mutations in GFAP, the gene encoding the major astrocyte intermediate filament protein. These mutations activate intracellular stress responses and change the astrocyte phenotype dramatically. They lead to astrocyte dysfunction that resembles a marked reactive astrocytosis and produces pathology in neurons, oligodendrocytes, and microglia. Indeed, the major genes upregulated in Alexander disease are immune-function genes, which activate microglia, and produce electrophysiological changes in neurons. As a pure astrocyte disease, Alexander disease gives us insights into mechanisms of pathological changes in astrocytes in epilepsy, strokes, infections, and neoplasms and helps us understand how astrocytes influence the other cells of the CNS. In other studies on astrocytes, our group has discovered molecular changes that underlie a well-known phenomenon of multinucleated astrocytes that accompany astrocyte reactions to many neurological disorders.

Departments and Divisions

  • Department of Psychiatry
    Division of Molecular Imaging and Neuropathology
  • Department of Pathology & Cell Biology
    Division of Anatomic Pathology

Board Certifications

  • Neuropathology

Areas of Expertise

  • Neuro-Pathology

Education and Training

  • MD, PhD, 1976 Neurobiology (PhD), New York University School of Medicine
  • Residency: Albert Einstein Medical Center
  • Fellowship: 1980 Albert Einstein Medical Center

Locations

  • 630 West 168th Street

    630 West 168th Street
    P&S 15-405
    New York, NY 10032
    Phone:
    (212) 305-3554
    Fax:
    (212) 305-4548
    Email:
    jeg5@cumc.columbia.edu
  • CUIMC/Presbyterian Hospital and Vanderbilt Clinic

    622 West 168th Street
    New York, NY 10032

Centers / Institutes / Programs

  • Herbert Irving Comprehensive Cancer Center
  • Taub Institute for Research on Alzheimer's Disease and the Aging Brain

Provider Affiliations

  • NewYork-Presbyterian / Columbia University Irving Medical Center

Insurance Programs

Please contact the provider's office directly to verify that your particular insurance is accepted.

  • AETNA [Aetna Signature Administrators, EPO, HMO, Medicare Managed Care, NYP Employee Plan, NY Signature, POS, PPO, Student Health]
  • CIGNA [EPO, Great West (National), HMO, POS, PPO]
  • Emblem/GHI [Medicare Managed Care, PPO]
  • Emblem/HIP [ConnectiCare, EPO, Essential Plan, HMO, Medicaid Managed Care, Medicare Managed Care, POS, PPO, Select Care (Exchange), Vytra]
  • Empire Blue Cross/Blue Shield [EPO, HMO, PPO]
  • Local 1199 [Local 1199]
  • MagnaCare (National) [MagnaCare]
  • Medicare [Railroad, Traditional Medicare]
  • Multiplan [Multiplan]
  • Oxford Health Plans [Freedom, Liberty]
  • RiverSpring [Special Needs]
  • UnitedHealthcare [Columbia University Employee Plan, Compass (Exchange), Empire Plan, HMO, Medicare Managed Care, POS, PPO]

This provider does not accept new patients

Contact Phone Number: 2123054531

Lab Locations

  • 630 West 168th Street

    630 West 168th Street
    P&S 15-405
    New York, NY 10032
    Phone:
    (212) 305-3554
    Fax:
    (212) 305-4548
    Email:
    jeg5@cumc.columbia.edu
  • CUIMC/Presbyterian Hospital and Vanderbilt Clinic

    622 West 168th Street
    New York, NY 10032

Contact Info

  • (212) 305-3554

Past Positions

  • 1976-1977 Research Associate, Department of Neurology, Albert Einstein College of Medicine, Bronx, NY
  • 1980 - 1985 Assistant Professor of Pathology, Albert Einstein College of Medicine, Bronx, NY
  • 1985 - 1987 Associate Professor of Pathology, Albert Einstein College of Medicine, Bronx, NY
  • 1987 - 1992 Associate Professor of Pathology (in Psychiatry), Columbia University College of Physicians & Surgeons, NY, NY
  • 1992 - 2015 Professor of Pathology & Cell Biology (in Psychiatry) and Director, Division of Neuropathology, Columbia University College of Physicians & Surgeons, NY, NY
  • 2015 - present Professor of Pathology & Cell Biology (in Psychiatry) and Director, Residency Training in Neuropathology, Columbia University College of Physicians & Surgeons, NY, NY

Committees / Societies / Memberships

Association for the Advancement of Science

Society for Neuroscience

American Assocation of Neuropathologists

American Association for Neurochemistry

Research Interests

  • Cell Specification and Differentiation
  • Glial Development and Pathology
  • Stem Cell Biology
  • Tuberous Sclerosis/Epilepsy/Autism Spectrum Disorders

Grants

  • Huntington’s Disease Society of America (Osama Al Dalahmah, PI, James E. Goldman, Faculty Mentor)
    "The Transcriptional Landscape of Huntington Disease; Exploring the Neuroprotective Potential of Astrocytes at The Single Cell Level"; 11/1/2019 – 10/31/2021.
  • Michael J Fox Foundation (James E. Goldman, PI)
    "Astrocyte Gene Expression in PD Interrogated using Single Cell Nuclear RNASeq". 02/12/2020 – 08/11/2021.
  • R01NS118179 NIH/NINDS (PI: Kuo; JE Goldman, Co-I)
    "Targeting cerebellar excitatory synapses for tremor progression". 07/01/2020 - 06/30/2025
  • William Rhodes and Louise Tilzer-Rhodes Center for Glioblastoma at NewYork-Presbyterian Hospital. (OA Dalahmah, V Menon, JE Goldman, Co-PIs) 09/01/20 – 12/31/2021
  • ASAP (Aligning Science Across Parkinson's). (D Sulzer, PI; JE Goldman, Collaborator)
    "Adaptive Immunity in the Etiology and Progression of Parkinson's Diseas". 10/1/2020 – 9/30/2023

NIH Grants

  • THE TRANSCRIPTIONAL LANDSCAPE OF HUNTINGTON DISEASE EXPLORING THE NEUROPROTECTIVE POTENTIAL OF ASTROCYTES AT THE SINGLE CELL LEVEL (Private)

    Nov 1 2019 - Oct 31 2021

    MITOCHONDRIAL DYSFUNCTION AND WHITE MATTER INJURY (Federal Gov)

    Sep 1 2016 - May 31 2021

    ASTROCYTE GENE EXPRESSION IN PD INTERROGATED USING SINGLE CELL NUCLEAR RNASEQ (Private)

    Oct 1 2019 - Mar 31 2021

    THE REGIONAL HETEROGENEITY OF HUNTINGTON S DISEASE PATHOLOGY: CLUES FROM DIVERSE ASTROCYTIC RESPONSE (Private)

    Aug 1 2019 - Jul 31 2020

    MOLECULAR MECHANISMS UNDERLYING THE EPILEPTOGENESIS AND SEIZURE PROGRESSION IN TUBEROUS SCLEROSIS COMPLEX 1 DEFICIENT MOUSE MODELS (Federal Gov)

    Sep 15 2015 - Sep 14 2018

    HGF: C-MET SIGNALING IN OLIGODENDROCYTE DEVELOPMENT AND ITS INHIBITION BY CD82 (Private)

    Oct 1 2013 - Sep 30 2016

    ALTERED ASTROCYTE-NEURON INTERACTIONS AND EPILEPTOGENESIS IN TUBEROUS SCLEROSIS COMPLEX DISORDER (Federal Gov)

    Jun 1 2012 - May 31 2015

    ALEXANDER DISEASE: CELLULAR AND MOLECULAR MECHANISMS (Federal Gov)

    Sep 20 2008 - Jun 30 2013

    ALEXANDER DISEASE: CELLULAR AND MOLECULAR MECHANISMS (Federal Gov)

    Sep 20 2008 - Jun 30 2012

    KAI1/CD82 REGULATES OLIGODENDROCYTE PROGENITOR MIGRATION AND DIFFERENTIATION (Private)

    Jul 1 2009 - Jun 30 2012

    ALEXANDER DISEASE: CELLULAR AND MOLECULAR MECHANISMS (Federal Gov)

    Sep 20 2008 - Jun 30 2012

    PATHOGENESIS OF TUBEROUS SCLEROSIS CORTICAL LESIONS (Federal Gov)

    May 1 2006 - May 2 2010

    ALEXANDER DISEASE--CELLULAR AND MOLECULAR MECHANISMS PROJECT CELLULAR PATHOLOGY OF ALEXANDER DISEASE (Federal Gov)

    Mar 1 2005 - Feb 28 2008

    THE FUNCTIONAL HETEROGENEITY OF THE OLIGODENDROCYTE PROGENITORS IN THE ADULT CNS (Private)

    Jul 1 2000 - Jun 30 2003

Publications

  • Thakur KT*, Miller EH*, Glendinning MD* ……. Agalliu D**, Uhlemann A-C**, Goldman JE**, Canoll PD**  COVID-19 Neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital (**Co-Senior authors).  Brain,  April 15, 2021. https://doi.org/10.1093/brain/awab148.
  • Al-Dalahmah O, Thakur K, Nordvig A, Prust M, Roth W, Lignelli A, Uhlemann A-C, Miller EH, Kunnath-Velayudhan S, Del Portillo A, Liu Y, Lin C-C, Hargus G, Teich AF, Hickman R, Tanji K, Vonsattel JP, Goldman JE, Faust P, Canoll P. Vasculopathy, neuronophagia, and microglial nodules in a SARS-CoV-2 patient with cerebellar hemorrhage.  Acta Neuropathol Commun, 8, 147 (2020). https://doi.org/10.1186/s40478-020-01024-2
  •  Sosunov A, Wu X,McGovern R, Mikell C, McKhann II GM*, Goldman JE* (2020) Abnormal mitosis in reactive astrocytes.  Acta Neuropathologica Comm 8:47 https://doi.org/10.1186/s40478-020-00919-4  (*Co-Senior authors).
  • Niatsetskaya Z, Sosunov S, Stepanova AA, Goldman JE, Galkin A, Neginskaya M, Pavlov E, and Ten V. Cyclophilin D-dependent oligodendrocyte mitochondrial ion leak contributes to neonatal white matter injury  J Clin Invest, (2020) https://doi.org/10.1172/JCI133082.
  • Al-Dalahmah O, Sosunov AA,l Shaik A, Ofori K, Liu Y, Vonsattel JP, Adorjan I, Menon V, Goldman JE. Single-nucleus RNA-seq identifies Huntington disease astrocyte states.  Acta Neuropathol Comm.  8:19, 2020 DOI: 10.1186/s40470-020-0880-]
  • Leskinen S,Flowers X, Thoene K, Anne-Catrin Uhlemann A-C, Goldman JE, and Hickman RA (2020) Meningomyeloencephalitis secondary to Mycobacterium haemophilum infection in AIDS.  Acta Neuropathol Commun 8:73  https://doi.org/10.1186/s40478-020-00937-2
  • Sapi E, Kasliwala R, Ismail H,  Torres JP, Oldakowski M, Markland S, Gaur G, Melillo A, Eisendle K, Liegner KB, Libien J, Goldman JE.  Long-term Persistence of Borrelia burgdorferi Antigens and DNA in Tissues of a Patient with Lyme Disease. Antibiotics. 8.pil: E183.  doi:10.3390/antibiotics8040183, 2019. 
  • Sosunov A, Olabarria M, and Goldman, JE:  Alexander Disease: an astrocytopathy that produces a leukodystrophy.  Brain Pathology 28:388-398, 2018
  • Sosunov AA, McKhann II GM, Goldman JE.  The Origin of Rosenthal Fibers and their Contributions to Astrocyte Pathology in Alexander Disease.  Acta Neuropathol. Communications, 5:27. DOI 10.1186/s40478-017-0425-9, 2017. PMID: 28359321
  • Olabarria M, Putilina M, Riemer EC, Goldman JE. Astrocyte pathology in Alexander Disease causes a marked inflammatory environment. Acta Neuropathol. 130: 469-486, 2015. DOI: 10.1007/s00401-015-1469-1 PMID: 26296699
  • Sosunov AA, McGovern RA, Mikell CB, Wu X, Coughlin DG, Crino PB, Weiner HL, Ghatan S, Goldman JE, McKhann GM. Epileptogenic but MRI-normal perituberal tissue in Tuberous Sclerosis Complex contains tuber-specific abnormalities. Acta Neuropathol Commun. 2015 Apr 2;3(1):17. doi: 10.1186/s40478-015-0191-5. PMID: 25853525.