James E. Goldman, MD, PhD

Board Certifications: 
Neuropathology
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Overview

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

Areas of Expertise / Conditions Treated

  • Neuro-Pathology

Academic Appointments

  • Professor of Pathology and Cell Biology (in Psychiatry)

Administrative Titles

  • Director, Neuropathology Fellowship Program

Hospital Affiliations

  • NewYork-Presbyterian / Columbia University Irving Medical Center

Gender

  • Male

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Insurance Accepted

Aetna

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  • Capital District Physician Health Plan

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  • Great West
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Emblem/HIP

  • ConnectiCare
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  • Essential Plan
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  • Medicaid Managed Care
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  • POS
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Local 1199

  • Local 1199

MagnaCare

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Multiplan

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MVP Health Care

  • Child/Family Health Plus
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  • Medicaid Managed Care

Oxford Health Plans

  • Freedom
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UnitedHealthcare

  • Columbia University Employee Plan
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  • Medicaid (Community Plan)
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Credentials & Experience

Education & Training

  • MD, PhD, 1976 Neurobiology (PhD), New York University School of Medicine
  • 1976 New York University School of Medicine
  • MD, PhD , 1976 NYU Langone Health / Tisch Hospital
  • Internship: 1978 Albert Einstein College of Medicine
  • Residency: Albert Einstein Medical Center
  • Residency: 1980 Montefiore Medical Center
  • Residency: 1980 Albert Einstein College of Medicine
  • Fellowship: 1980 Albert Einstein Medical Center

Board Certifications

  • Neuropathology

Research

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.

Research Interests

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

Grants

“Mitochondrial Dysfunction and White Matter Injury”

1R01 NS099109-01 (NIH/NINDS) (V Ten, PI, JE Goldman, Co-PI). 9/1/2016 – 8/31-2021

The goals of this project are to model and to understand the mechanisms underlying hypomyelination in the neonatal CNS caused by intermittant hypoxia.

“The regional heterogeneity of Huntington's disease pathology: Clues from diverse astrocytic responses”.

Hereditary Disease Foundation (OA Dalahmah, PI, JE Goldman, Sponsor) 7/20/2019 – 7/19/2020

The goal is to use single cell nuclear RNASeq on nuclei isolated from the neostriatum and nucleus accumbens from fresh frozen Huntington Disease and control brain tissues to determine changes in single cell gene expression in Huntington Disease.

“The Transcriptional Landscape of Huntington Disease; Exploring the Neuroprotective Potential of Astrocytes at The Single Cell Level”

Huntington’s Disease Society of America (OA Dalahmah, PI, JE Goldman, Sponsor) 11/1/2019 – 10/31/2021

The goal is to use single cell nuclear RNASeq on nuclei isolated from the cingulate cortex from fresh frozen Huntington Disease and control brain tissues to determine changes in single cell gene expression in Huntington Disease. Here we will examine tissues from patients in the early, mid, and late stages of Huntington’s Disease.

"Astrocyte Gene Expression in PD Interrogated using Single Cell Nuclear RNASeq."

Michael J. Fox Foundation. (JE Goldman, PI) 02/12/2020 – 08/11/2021.

The goal is to use single cell nuclear RNASeq on nuclei isolated from fresh frozen brain tissues from patients with Parkinson disease with GBA mutations, Parkinson disease without GBA mutations, and control brain tissues to determine changes in single cell gene expression in Parkinson Disease and to examine why GBA mutations increase risk of developing Parkinson Disease. The focus is on changes in astrocyte gene expression, but with this technique we will determine gene expression changes in all cell types.

Targeting cerebellar excitatory synapses for tremor progression

R01NS118179 (PI: Kuo; JE Goldman, Co-I) 07/01/2020 - 06/30/2025

The proposed research will take the recent genetic and neuropathological discoveries of ET into functional understanding how structural and molecular changes in the brain can lead to tremor, and the knowledge gained will serve as foundation for therapy development to slow down thedisease progression and to prevent disability.

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

This grant is to look at the transcriptional changes that occur in neurons and glial cells at the periphery of the malignant glioma, glioblastoma multiforme. In this way we hope to understand the inflammatory environment around the tumor, reasons for the development of seizures, and how the peripheral regions may predispose tumor cells to migrate away from the main tumor area.

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.