James E. Goldman, MD, PhD

Board Certifications: 
Neuropathology
Profile Headshot

Overview

Areas of Expertise / Conditions Treated

Neuro-Pathology

Academic Appointments

  • Professor of Pathology and Cell Biology (in Psychiatry)

Administrative Titles

  • Director, Neuropathology Fellowship Program

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, 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.  

In collaboration with Guomei Tang and David Sulzer of Neurology, Guy McKhann 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, a disease characterized by seizures and commonly by autism-spectrum disorders, in which cells have constitutively activated mTOR. RNASeq and ribosomal profiling and footprinting give us many genes that 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.

Email: jeg5@cumc.columbia.edu

Hospital Affiliations

  • NewYork-Presbyterian/Columbia

Gender

  • Male

Insurance Accepted

Aetna

  • EPO
  • HMO
  • Medicare Managed Care
  • NY Signature
  • NYP Employee Plan
  • POS
  • PPO
  • Signature Administrators
  • Student Health

Cigna

  • EPO
  • Great West
  • 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

  • Blue Access (Exchange)
  • EPO
  • Gatekeeper (Exchange)
  • HMO
  • Medicare Managed Care
  • Pathway (Exchange)
  • POS
  • PPO

Local 1199

  • Local 1199

MagnaCare

  • MagnaCare

Medicare

  • Medicare

Multiplan

  • Multiplan

MVP Health Care

  • Child/Family Health Plus
  • Essential Plan
  • HMO
  • Medicaid Managed Care

Oxford Health Plans

  • Freedom
  • HMO
  • Liberty
  • Medicare Managed Care

UnitedHealthcare

  • Columbia University Employee Plan
  • Compass (Exchange)
  • HMO
  • Medicaid (Community Plan)
  • Medicare Managed Care
  • POS
  • PPO

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

Credentials & Experience

Education & Training

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

Board Certifications

  • Neuropathology

Research

Research Interests

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

Grants

THE REGIONAL HETEROGENEITY OF HUNTINGTON'S DISEASE PATHOLOGY: CLUES FROM DIVERSE ASTROCYTIC RESPONSES

Hereditary Disease Foundation 

Project Dates: July, 2019 to July, 2020

THE TRANSCRIPTIONAL LANDSCAPE OF HUNTINGTON DISEASE; EXPLORING THE NEUROPROTECTIVE POTENTIAL OF ASTROCYTES AT THE SINGLE CELL LEVEL

Huntington’s Disease Society of America 

Project Dates:  Nov 1 2019 to Oct 31 2021

MITOCHONDRIAL DYSFUNCTION AND WHITE MATTER INJURY (Federal Gov)

Sep 1 2016 - May 31 2021

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

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

Selected Publications

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.

Tang G, Gudsnuk K, Kuo SH, Cotrina ML, Rosoklija G, Sosunov A, Sonders MS, Kanter E, Castagna C, Yamamoto A, Yue Z, Arancio O, Peterson BS, Champagne F, Dwork AJ, Goldman J, Sulzer D. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.  Neuron. 2014 Sep 3;83(5):1131-43. doi: 10.1016/j.neuron.2014.07.040. Epub 2014 Aug 21. Erratum in: Neuron. 2014 Sep 17;83(6):1482. PMID: 25155956

Mayer JA, Griffiths IR, Goldman JE, Smith CM, Cooksey E, Radcliff AB, Duncan ID. Modeling the natural history of Pelizaeus-Merzbacher disease. Neurobiol Dis. 2015 Mar;75:115-30. doi: 10.1016/j.nbd.2014.12.023. Epub 2015 Jan 3. PMID: 25562656.

Collins-Praino LE, Francis YI, Griffith EY, Wiegman AF, Urbach J, Lawton A, Honig LS, Cortes E, Vonsattel JP, Canoll PD, Goldman JE, Brickman AM. Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity. Acta Neuropathol Commun. 2014 Aug 17;2:83. doi: 10.1186/PREACCEPT-3091772881321882. PMID: 25129614.

Walker AK, Daniels CM, Goldman JE, Trojanowski JQ, Lee VM, Messing A. Astrocytic TDP-43 pathology in Alexander disease. J Neurosci. 2014 May 7;34(19):6448-58. doi: 10.1523/JNEUROSCI.0248-14.2014. PMID: 24806671.

Sosunov AA, Wu X, Tsankova NM, Guilfoyle E, McKhann GM 2nd, Goldman JE. Phenotypic heterogeneity and plasticity of isocortical and hippocampal astrocytes in the human brain. J Neurosci. 2014 Feb 5;34(6):2285-98. doi: 10.1523/JNEUROSCI.4037-13.2014. PMID: 24501367.

Shigemoto-Mogami Y, Hoshikawa K, Goldman JE, Sekino Y, Sato K. Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci. 2014 Feb 5;34(6):2231-43. doi: 10.1523/JNEUROSCI.1619-13.2014. PMID: 24501362.

Collins-Praino LE, Francis YI, Griffith EY, Wiegman AF, Urbach J, Lawton A, Honig LS, Cortes E, Vonsattel JP, Canoll PD, Goldman JE, Brickman AM. Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity. Acta Neuropathol Commun. 2014 Aug 17;2(1):83. doi: 10.1186/s40478-014-0083-0. PMID: 25927863.

Mela A, Goldman JE. CD82 blocks cMet activation and overcomes hepatocyte growth factor effects on oligodendrocyte precursor differentiation. J Neurosci. 2013 May 1;33(18):7952-60. doi: 10.1523/JNEUROSCI.5836-12.2013. PMID: 23637186.

Tang G, Gutierrez Rios P, Kuo SH, Akman HO, Rosoklija G, Tanji K, Dwork A, Schon EA, Dimauro S Goldman J,  Sulzer D. Mitochondrial abnormalities in temporal lobe of autistic brain. Neurobiol Dis. 2013 Jun;54:349-61. doi: 10.1016/j.nbd.2013.01.006. Epub 2013 Jan 17. PMID: 23333625.

Sosunov AA, Guilfoyle E, Wu X, McKhann GM 2nd, Goldman JE. Phenotypic conversions of "protoplasmic" to "reactive" astrocytes in Alexander disease. J Neurosci. 2013 Apr 24;33(17):7439-50. doi: 10.1523/JNEUROSCI.4506-12.2013. PMID: 23616550.

Jang ES, Goldman JE. Pax6 expression is sufficient to induce a neurogenic fate in glial progenitors of the neonatal subventricular zone. PLoS One. 2011;6(6):e20894. doi: 10.1371/journal.pone.0020894. Epub 2011 Jun 17. PMID: 21698109.

Quan PL, Wagner TA, Briese T, Torgerson TR, Hornig M, Tashmukhamedova A, Firth C, Palacios G, Baisre-De-Leon A, Paddock CD, Hutchison SK, Egholm M, Zaki SR, Goldman JE, Ochs HD, Lipkin WI. Astrovirus encephalitis in boy with X-linked agammaglobulinemia. Emerg Infect Dis. 2010 Jun;16(6):918-25. doi: 10.3201/eid1606.091536. PMID: 20507741.

Tian R, Wu X, Hagemann TL, Sosunov AA, Messing A, McKhann GM, Goldman JE. Alexander disease mutant glial fibrillary acidic protein compromises glutamate transport in astrocytes.  
J Neuropathol Exp Neurol. 2010 Apr;69(4):335-45. doi: 10.1097/NEN.0b013e3181d3cb52. PMID: 20448479.

Tang G, Perng MD, Wilk S, Quinlan R, Goldman JE. Oligomers of mutant glial fibrillary acidic protein (GFAP) Inhibit the proteasome system in alexander disease astrocytes, and the small heat shock protein alphaB-crystallin reverses the inhibition. J Biol Chem. 2010 Apr 2;285(14):10527-37. doi: 10.1074/jbc.M109.067975. Epub 2010 Jan 28. PMID: 20110364.

Mela A, Goldman JE. The tetraspanin KAI1/CD82 is expressed by late-lineage oligodendrocyte precursors and may function to restrict precursor migration and promote oligodendrocyte differentiation and myelination. J Neurosci. 2009 Sep 9;29(36):11172-81. doi: 10.1523/JNEUROSCI.3075-09.2009. PMID: 19741124.

Lin G, Mela A, Guilfoyle EM, Goldman JE. Neonatal and adult O4(+) oligodendrocyte lineage cells display different growth factor responses and different gene expression patterns.
J Neurosci Res. 2009 Nov 15;87(15):3390-402. doi: 10.1002/jnr.22065. PMID: 19360905.

Lin G, Goldman JE. An FGF-responsive astrocyte precursor isolated from the neonatal forebrain. Glia. 2009 Apr 15;57(6):592-603. doi: 10.1002/glia.20788. PMID: 19031440.

Canoll P, Goldman JE. The interface between glial progenitors and gliomas. Acta Neuropathol. 2008 Nov;116(5):465-77. doi: 10.1007/s00401-008-0432-9. Epub 2008 Sep 11. Review. PMID: 18784926.

Tang G, Yue Z, Talloczy Z, Goldman JE. Adaptive autophagy in Alexander disease-affected astrocytes. Autophagy. 2008 Jul;4(5):701-3. Epub 2008 Apr 3. Review. PMID: 18414043.

Tang G, Yue Z, Talloczy Z, Hagemann T, Cho W, Messing A, Sulzer DL, Goldman JE. Autophagy induced by Alexander disease-mutant GFAP accumulation is regulated by p38/MAPK and mTOR signaling pathways. Hum Mol Genet. 2008 Jun 1;17(11):1540-55. doi: 10.1093/hmg/ddn042. Epub 2008 Feb 14. PMID: 18276609.

Ivkovic S, Canoll P, Goldman JE. Constitutive EGFR signaling in oligodendrocyte progenitors leads to diffuse hyperplasia in postnatal white matter. J Neurosci. 2008 Jan 23;28(4):914-22. doi: 10.1523/JNEUROSCI.4327-07.2008. PMID: 18216199.