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Oregon Health & Science Univ
Molecular & Medical Genetics
Mail Code: L103
3181 SW Sam Jackson
Park Road
Portland, OR 97239
503-494-7703
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David Koeller, Ph.D. - Associate Professor
Oregon Health & Science University
3181 SW Sam Jackson Park Road
Mail Code CDRCP
Portland, OR 97239
E-Mail: koellerd@ohsu.edu
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RESEARCH
Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism that causes a severe neurologic disease associated with degeneration of the caudate and putamen nuclei, which are in a region of the brain called the striatum. This area of the brain is involved in the involuntary control of movement and muscle tone, and as a result of the neuronal damage patients with GA-I develop a severe movement disorder. The biochemical defect in GA-I results in the accumulation of high levels of glutaric and 3-hydroxyglutaric acids in the blood and brain, which are responsible for the neurologic damage. However, it is not know whether the elevations of glutaric and 3-hydroxyglutaric acids seen in the central nervous system are generated by the brain itself, or are derived from the blood stream.
We have created a mouse model of GA-I via gene targeting in ES cells and are using these mice to study pathophysiology and develop novel treatments. Our hypothesis is that curing the enzymatic defect in the liver, and reducing blood levels of glutaric and 3-hydroxyglutaric acids, will prevent the neurologic damage. If this is true, it would mean that liver directed gene and/or cell therapy will be an effective treatment for patients affected with this disorder. Currently we are testing our hypothesis using a gene therapy approach, using anadeno-associated virus to deliver a cDNA to the liver.
SELECT PUBLICATIONS Koeller DM, Woontner M, Crnic LS, Kleinschmidt-DeMasters B, Stephens J, Hunt EL, Goodman SI (2002). Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I. Hum Mol Genet11(4):347-57. Schueck ND, Woontner M, Koeller DM (2001). The role of the mitochondrion in cellular iron homeostasis. Mitochondrion:1:51-60. Allikmets R, Raskind WH, Hutchinson A, Schueck ND, Dean M, Koeller DM (1999). Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hu Mol Genet 8(5):743-9.
For more information on publications, contact the faculty member or search PubMed.
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