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Eric A Schon
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Professor of Genetics and Development
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| Address: |
1150 St. Nicholas Avenue Room 307 New York NY 10032 |
| Phone: |
212-851-5532 |
| Fax: |
212-305-3986 |
E-mail:
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eas3@columbia.edu
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Education and Training:
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Ph.D. 1982, University of Cincinnati
Postdoctoral Fellow 1982, Harvard University
Associate Research Scientist 1984, Columbia University
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Affiliations:
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 Department of Genetics and Development
Department of Neurology
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Training Activities:
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Department of Genetics & Development
MD/PhD Program
Integrated Program in Cellular, Molecular and Biophysical Studies
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Research Summary:
(800 words, max)
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Mitochondrial genetics and the molecular basis of human mitochondrial disease.
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Current Research:
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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.
Mitochondrial diseases have turned out to be equally unusual. There are maternally-inherited, mendelian-inherited, sporadic, and even environmentally induced mitochondrial disorders, most of which are either severely debilitating or fatal. We are studying the molecular basis of a number of these diseases, most of which are heteroplasmic (i.e. both mutant and wild-type mtDNAs coexist in varying proportions in the same patient), using a novel tissue culture system called "rho cells." These cells contain mitochondria, but the mitochondria are completely devoid of mtDNAs, and are thus respiratorily deficient. We have transferred heteroplasmic mitochondria from patients to these rho cells, thereby creating 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 are using cybrid technology not only to study genotype phenotype relationships, but also to ask basic questions about mitochondrial biogenesis (e.g. mitochondrial fusion and exchange of genetic information).
We have begun a project on mitochondrial gene therapy, in order to ameliorate the effects of a known pathogenic (and fatal) mtDNA mutation that affects ATP synthesis. In addition, we are trying to make the first "transmitochondrial" mouse model of a human mtDNA disease. |
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Publications:
(6 max)
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1. DiMauro S, Hirano M, Schon EA.: (2006) Approaches to the treatment of mitochondrial diseases. Muscle Nerve 34(3): 265-283
2. Zanssen S, Schon EA.: (2005) Mitochondrial DNA mutations in cancer. PLoS Med 2(11): e401
3. 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(15): 15202-15211
4. Tay SK, Nesti C, Mancuso M, Schon EA, Shanske S, Bonilla E, Davidson MM, Dimauro S.: (2004 ) Studies of COX16, COX19, and PET191 in human cytochrome-c oxidase deficiency. Arch Neurol 61(12): 1935-1937
5. Santra S, Gilkerson RW, Davidson M, Schon EA.: (2004) Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells. Ann Neurol 56(5): 662-669
6. Schon EA.: (2004) Complements of the house. J Clin Invest 114(6): 760-772
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URL for lab page:
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