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Eric A. Schon, PhD

  • Lewis P. Rowland Professor of Neurology (in Genetics and Development)
Eric A. Schon, PhD
Eric Schon is the Lewis P. Rowland Professor of Neurology, and holds a joint appointment as a Professor in the Department of Genetics and Development. After receiving a B.S. in Chemical Engineering from Columbia University, he worked for 10 years for the Procter & Gamble Company in Cincinnati, OH as a Technical Brand Manager. He left industry in 1979 and received his Ph.D. in Biological Chemistry from the University of Cincinnati. He did his postdoctoral work at Harvard University and at Columbia University.

Mitochondria are unique among the constituents of the eukaryotic cell in that they are semi-autonomous organelles that contain their own genetic machinery. As such, they operate under the dual genetic controls of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Mitochondrial genetics differs markedly from mendelian genetics, because first, mitochondria are inherited exclusively from the mother, and second, there are hundreds or thousands of mitochondria (and mtDNAs) per cell. In addition, organellar division and mtDNA replication are stochastic processes unrelated to the cell cycle; and mtDNA gene organization, DNA replication, RNA transcription, and protein translation all have a prokaryotic "look" about them. This latter feature is no surprise, given that mitochondria were once bacteria that were taken up by the proto-eukaryotic cell early in evolution. Biochemically, the most relevant aspect of mitochondrial function is the production of oxidative energy via the respiratory chain and oxidative phosphorylation.

Mitochondria are semi-autonomous organelles that contain their own genetic machinery. As such, they operate under the dual genetic controls of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Mitochondrial genetics differs markedly from mendelian genetics, because first, mitochondria are inherited exclusively from the mother, and second, there are hundreds or thousands of mitochondria (and mtDNAs) per cell. Biochemically, the most relevant aspect of mitochondrial function is the production of oxidative energy via the respiratory chain and oxidative phosphorylation. There are maternally-inherited, mendelian-inherited, sporadic, and even environmentally-induced mitochondrial disorders, most of which are fatal. We are studying the molecular basis of a number of these diseases, often using cytoplasmic hybrids, or "cybrids," that contain known proportions of mutant or wild-type mtDNAs in clonal cell lines that have no contaminating mtDNA background. We have also begun a project on treating mtDNA-based disease using pharmacoligical approaches aimed at "shifting heteroplasmy" in order to restore respiratory function in patient-derived cells. Most recently we have become interested in the pathogenesis of Alzheimer disease, and have discovered that presenilin-1, presenilin-2, and gamma-secretase activity itself, are located predominantly in a specialized subcompartment of the ER that is physically and biochemically connected to mitochondria, called mitochondria-associated ER membranes (MAM). We have found that cells from AD patients have massively increased ER-mitochondrial communication, which may help explain many of the seemingly unrelated features of the disease. We believe that this hyperconnectivity plays a fundamental role in the pathogenesis of AD, with implications for both diagnosis and treatment of this devastating disorder.

Mitochondrial genetics and the molecular basis of human mitochondrial disease.

Departmental Appointments

  • Department of Neurology
    Division of Neuromuscular Medicine

Education & Training

  • PhD, 1982 Biological Chemistry, University of Cincinnati College of Medicine

Centers/Institutes/Programs

  • H. Houston Merritt Center for Muscular Dystrophy and Related Disorders

Honors & Awards

1968: Phi Lambda Upsilon, honorary chemistry society. 1981: First place winner, University of Cincinnati College of Medicine Graduate Student Research Competition. 1986: Sponsor of the winner of the S. Weir Mitchell Award of the American Academy of Neurology: "Transthyretin: a choroid plexus-specific protein in human brain". 1986: Prize for Best Poster, International Symposium on Molecular and Genetic Aspects of Inherited Diseases of the Nervous System and Skeletal Muscle, Saint-Vincent, Italy: "Cytochrome c oxidase deficiency: a molecular genetic approach." 1989: Lamport Award for Excellence in Research, Columbia University. 1992: The Sigrid Juselius Lecture, "Analysis of pathogenic mitochondrial DNA mutations in a novel tissue culture system," presented at the 7th European Bioenergetics Conference, Helsinki, Finland. 1997: The Laura Dribin Lecture, "Molecular genetics of human mitochondrial disease," presented at Children's Hospital of Philadelphia, Philadelphia, PA.

Research Interests

  • Mitochondrial genetics and the molecular basis of human mitochondrial disease

NIH Grants

  • MITOCHONDRIAL ENCEPHALOMYOPATHIES: APPROACHES TO TREATMENT (Federal Gov)

    Sep 30 2014 - May 31 2019

    DEVELOPMENT OF A COMPLETE PIPELINE FOR MELAS DRUG DISCOVERY (Private)

    Dec 17 2015 - Dec 16 2018

    APPROACHES TO DIAGNOSIS AND TREATMENT OF ALZHEIMER DISEASE (Private)

    Jun 1 2017 - May 31 2018

    MECHANISM OF ACTION OF PRDM16 IN HEMATOPOIETIC STEM CELLS (Federal Gov)

    Jan 1 2013 - Dec 31 2017

    DEVELOPMENT OF METHODS TO INTRODUCE EXOGENOUS MTDNA INTO MAMMALIAN MITOCHONDRIA (Private)

    Dec 17 2015 - Dec 16 2017

    GENETIC SUSCEPTIBILITY TO AGE-RELATED MACULAR DEGENERATION (Federal Gov)

    May 1 2001 - Aug 31 2016

    THE ROLE OF APOE IN ALZHEIMER DISEASE AND IN TRAUMATIC BRAIN INJURY (Federal Gov)

    Jun 1 2015 - Feb 29 2016

    MITOCHONDRIAL ENCEPHALOMYOPATHIES AND MENTAL RETARDATION (Federal Gov)

    Dec 1 1996 - Feb 29 2016

    TREATMENT STRATEGIES FOR HUMAN MITOCHONDRIAL DISEASE (Private)

    Feb 1 2013 - Jan 31 2016

    DEVELOPMENT OF A COMPLETE PIPELINE FOR MELAS DRUG DISCOVERY (Private)

    Jan 1 2014 - Dec 31 2015

    TREATMENT STRATEGIES FOR HUMAN MITOCHONDRIAL DISEASE (Private)

    Nov 1 2012 - Oct 31 2015

    INCREASED ER-MITOCHONDRIAL COMMUNICATION IN THE PATHOGENESIS OF ALZHEIMER DISEASE (Federal Gov)

    Jul 1 2012 - Feb 28 2015

    MITOCHONDRIA-ASSOCIATED MEMBRANES IN ALZHEIMER DISEASE (Private)

    Nov 1 2009 - Nov 2 2014

    MITOCHONDRIA-ASSOCIATED MEMBRANES IN ALZHEIMER DISEASE: A NE W TARGET FOR DRUG DISCOVERY (Private)

    Nov 1 2011 - Oct 31 2012

    PHARMACOLOGICAL APPROACHES TO TREAT HUMAN MITOCHONDRIAL DISE ASES (Private)

    Jul 1 2009 - Jun 30 2012

    PHARMACOLOGICAL APPROCHES TO TREAT HUMAN MITOCHONDRIAL DISEA SES (Private)

    Jul 1 2009 - Jun 30 2012

    MITOCHONDRIA-ASSOCIATED MEMBRANES IN ALZHEIMER DISEASE: A NE W TARGET FOR DRUG DISCOVERY (Private)

    Jan 1 2010 - Jun 30 2011

Publications

1. Williams JC, Sue C, Banting GS, Yang H, Glerum DM, Hendrickson WA, Schon EA: (2005) Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein.  J. Biol. Chem.   280: 15202-15211 

2. Santra S, Gilkerson RW, Davidson M, Schon EA: (2004) Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells.  Ann Neurol  56: 662-669 

3. Gilkerson RW, Schon EA, Hernandez E, Davidson MM: (2008) Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation.  J. Cell Biol.  181: 1117-1128 

4. Area-Gomez E, de Groof AJC, Boldogh I, Bird TD, Gibson GE, Koehler CM, Yu WH, Duff KE, Yaffe MP, Pon LA, Schon EA: (2009) Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria.  Am. J. Pathol.  175: 1810-1816 

5. Area-Gomez E, Lara Castillo MdC, Tambini MD, de Groof AJC, Madra M, Ikenouchi J, Umeda M, Bird TD, Sturley SL, Schon EA: (2012) Upregulated function of mitochondria-associated ER membranes in Alzheimer disease.  EMBO J.  31: 4106-4123 

6. Guardia-Laguarta C, Area-Gomez E, Rüb C, Liu Y, Magrané J, Becker D, Voos W, Schon EA, Przedborski S: (2014) α-Synuclein is localized to mitochondria-associated ER membranes.  J. Neurosci.  34: 249-259