Mitochondrial genetics and disease
The research in my laboratory is two-fold: to understand the basic biology of mammalian mitochondria and to develop strategies to understand and treat human mitochondrial disease.
On the more basic side, we are trying to understand how mitochondrial DNAs (mtDNAs), which are packaged in protein-DNA aggregates called nucleoids that are attached to the mitochondrial inner membrane, are inherited during the process of cell division. We are also trying to identify genes controlling mitochondrial proliferation in muscle (i.e. formation of "ragged-red fibers").
On the more applied side, we have developed a gene-therapy approach to treat diseases resulting from mutations in mtDNA-encoded polypeptides, in which an mtDNA-encoded gene is engineered to be expressed as a nucleus-encoded cytoplasmic protein that is targeted specifically to mitochondria ("allotopic expression"). We are also working on pharmacological approaches to treatment, including a "heteroplasmic shifting" strategy that uses ketogenic media to reduce the proportion of mutated mtDNAs in patient cells.
Mitochondrial diseases can also be caused by mutations in nuclear genes which are inherited in a classical mendelian manner, such as the fatal infantile encephalomyopathies due to mutations in SCO1 and SCO2, two putative copper chaperones required for the assembly of cytochrome c oxidase (complex IV of the mitochondrial respiratory chain). We have crystallized SCO1 and have found that it may be also be a mitochondrial redox sensor, and are now studying SCO2 in tissue culture and in knock-out and knock-in mice in order to test this hypothesis.
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.
| 1968 |
B.S., Chemical Engineering, Columbia University, New York, NY |
| 1973 |
M.S., Chemical Engineering, University of Cincinnati, Cincinnati, OH |
| 1982 |
Ph.D., Biological Chemistry, University of Cincinnati, Cincinnati, OH |
| 1983 |
Postdoctoral Fellow, Harvard University, Boston, MA |
| 1984 |
Associate Research Scientist, Columbia University, New York, NY |
| 1968 |
Phi Lambda Upsilon, honorary chemistry society. |
| 1981 |
First place winner, University of Cincinnati Graduate Student Research Competition. |
| 1986 |
Prize for Best Poster, International Symposium on Molecular Disease, Aosta, Italy |
| 1989 |
Lamport Award for Excellence in Research, Columbia University. |
| 1992 |
The Juselius Lecture, 7th European Bioenergetics Conference,Helsinki, Finland. |
| 1997 |
The Laura Dribin Lecture, Children's Hospital of Philadelphia, Philadelphia, PA. |
| 2000 |
Keynote speaker, Keystone Symposium, Santa Fe, NM. |
| 2006 |
Keynote speaker, meeting on Mitochondrial Function and Dysfunction, Israel. |
| 1995-98 |
Scientific Advisory Committee, Muscular Dystrophy Association |
| 2001 |
Scientific Advisory Committee, Familial Dysautonomia Foundation |
| 2002 |
Scientific Advisory Committee, United Mitochondrial Disease Foundation |
| 2003 |
Associate Editor, Journal of Clinical Investigation |
| 2004 |
Section Editor, Biochomica et Biophysica Acta |
- Schon EA, Rizzuto R, Moraes CT, Nakase H, Zeviani M, DiMauro S (1989). A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA. Science 244, 346-349.
- Evans, MJ, Gurer C, Loike, JD, Schnieke, AE, and Schon EA (1999). Mitochondrial DNA genotypes in nuclear transfer-derived cloned sheep. Nature Genet. 23, 90-93.
- Manfredi G, Fu J, Ojaimi J, Sadlock JE, Kwong JQ, Guy J, Schon EA (2002). Rescue of an ATP synthesis deficiency in mtDNA-mutant human cells by transfer of MTATP6, a mtDNA-encoded gene, to the nucleus. Nature Genet. 25, 394-399.
- DiMauro S, Schon EA (2003). Mitochondrial respiratory chain diseases. N. Engl. J. Med. 348, 2656-2668.
- Gajewski CD, Yang Y, Schon EA, Manfredi G (2003). New insights into the bioenergetics of mitochondrial disorders using intracellular ATP reporters. Mol. Biol. Cell 3628-3635.
- 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, 15202-152011.
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