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Education: B.A. in Biology, University of Texas, 1964 M.S. in Botany, Miami University, Ohio, 1966 Ph.D. in Biochemistry, Michigan State University, 1971 Research Interests: Peroxisomes are subcellular compartments that house oxidations that produce hydrogen peroxide. This occurs in most eukaryotic organisms including yeasts, plants and animals. Peroxisomes in yeast allow them to metabolize hydrocarbons and methanol. Their two main functions in plants are photorespiration in leaves and the conversion of oils to sugars in germinating seeds. In humans peroxisomes are responsible for the oxidation of certain dietary hydrocarbons and several human diseases result from genetic defects in peroxisomal function. We are investigating the consequences of the oxidative processes that occur in peroxisomes, using germinating castor bean (Ricinus communis) as a model system for our biochemical studies.
Currently, Mimi Kwak an MS student and Thy Nguyen an undergraduate are working on the oxidative damage of proteins within peroxisomes. We have devised ways to detect the extent of oxidation of individual proteins and to determine how this damage affects the functions of the proteins. The hypothesis under consideration is that proteins contained within peroxisomes are resistant to oxidation and retain functions despite oxidative damage. Protein oxidation is of broad significance in biology because it is thought to be one of the main consequences of aging. Thus, controlling oxidation can prolong the life and health of an organism.
RECENT PUBLICATIONS Nguyen AT, Donaldson RP. 2005 Metal-catalyzed oxidation induces carbonylation of peroxisomal proteins and loss of enzymatic activities. Arch Biochem Biophys. 2005 Jul 1;439(1):25-31. Donaldson, RP, Karyotou, K, Assadi, M, Olcum, T. 2000. Peroxisomes
and glyoxysomes in plants. Encyclopedia of Life Sciences. Internet
publication of Nature/McMillan Press. Wolins, NE, Donaldson, RP 1997 Binding of the peroxisomal protein
targeting sequence SKL is specified by a low-affinity site in castor
bean glyoxysomal membranes. A domain next to the SKL binds to a
high-affinity site. Plant Physiol. 113:943-949. Del Rio, LA, Donaldson, RP 1995 Production of superoxide radicals in glyoxysomal membranes from castor bean endosperm. J. Plant Physiol. 146:283-287 Wolins, NE, Donaldson, RP 1994 Specific binding of the peroxisomal
protein targeting sequence to glyoxysomal membranes. J. Biol. Chem.
269: 1149-1153 Donaldson, RP, Luster, DG 1991 Multiple forms of plant cytochromes P-450.Plant Physiol. 96:669-674. Alani, AA, Luster, DG, Donaldson, RP 1991 Development of ER and glyoxysomal membrane redox activities during castor bean germination. Plant Physiol. 94: 1842-1848. Lyons, HT, Kharroubi, A., Wolins, N., Tenner, S., Chanderbhan ,R.F., Fiskum, G., Donaldson, R.P. 1991. Elevated cholesterol and decreased sterol carrier protein-2 in peroxisomes from AS-30D hepatoma compared to normal rat liver. Arch. Biochem. Biophys. 285: 238-245. Bowditch MI, Donaldson RP 1990. Ascorbate free radical reduction by glyoxysomal membranes. Plant Physiol 94; 531-537 Mangurian, LP, RP Donaldson 1989 Development of peroxisomal beta-oxidation
enzymes in brown adipose tissue of perinatal rabbits. Biology of
the Neonate 57:349-357. Bisc 14 - Introductory Biology: Cell and Molecules - for science majors and premedical students, also co-taught with Dr. Packer. Bisc 105 - Plant Biochemistry - for students who have completed Bisc 14 and Chem 12. Also, maybe taken for graduate credit. Bisc 106 - Special Topics in Biochemistry - co-taught with faculty from the Chemistry and Biochemistry Departments. Same as Bioc 102 and Chem 162. A second semester biochemistry course designed to follow “Biochemistry” Bisc 103 for undergraduates. Bisc 183 - Biology of Proteins - this may be taken by students who have Bisc 14, Chem 12 or the AP equivalent. This is being offered for the first time in Fall 2003. The course concerns the structures, functions and computational aspects of the 1000’s of different proteins, some being involved in cancers, muscle degeneration and infectious diseases. This course has been developed as part of the Howard Hughes Medical Institute undergraduate science education program to prepare students for research internships during the academic year and summer. BMSC 210(Course Bulletin not up yet)- Biomedical Science Core: Macromolecular Interactions – Proteins - selected lectures. This is the first course of the full year core sequence taken by PhD students entering any of the six PhD programs in the Institute for Biomedical Sciences. CS 177 - Introduction to Bioinformatics - selected lectures, also part of the Hughes undergraduate program. Knowledge of bioinformatics is very useful in research internships. Computational Molecular Biology Workshop – co-taught with
Dr. Frank Turano. An intensive 2.5 week laboratory course to prepare
students for the Hughes summer internships. The course begins in
May and the internships continue for 10 weeks. Students may apply
as early as their freshman year (http://www.bioinformatics.gwu.edu/).
Yoon (Mimi) Kwak – current MS student, Topic: The sensitivity of peroxisomal catalase to oxidation. Annie Thy Nguyen – current BS student, Topic: Quantitative determination of protein oxidation in peroxisomes”. Ahdeah Pajoohesh-Ganji – current PhD Student co-directed with Dr. M. A. Stepp, GW Medical Center, Department of Anatomy and Cell Biology. Topic: Integrins in corneal wound healing. Elizabeth Nies-Kraske – current PhD Student co-directed with Dr. M. Dybul, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases. Topic: Molecular mechanisms of drug resistance of Human Immunodeficiency Virus. Tulin Olcum Yanik – PhD 2002, “A Protective Association Between Catalase and Isocitrate Lyase in Peroxisomes” Masoumeh (Simin) Assadi – PhD 2001, “Malate synthase C-terminal peptide interaction with its peroxisomal targeting receptor/s in castor bean” Konstantina Karyotou – PhD 2000, “Ascorbate assisted
free radical scavenging in peroxisomal membranes: an antioxidant
system in plants” WWW Links of Interest: http://www.bioinformatics.gwu.edu This site provides an overview of undergraduate and graduate programs in Bioinformatics. These programs are cooperative efforts of faculty from the Biology Department, the Computer Science Department in the School of Engineering and the Biochemistry Dept. in the GW Medical The site also gives information about the summer HHMI undergraduate research internships. http://www.gwumc.edu/ibs/ Describes the GW Institute for Biomedical Sciences and links to the six associated PhD programs, including the Genetics Program. Information about the Biomedical Sciences Core Curriculum (BMSC) courses taken by PhD students during their first year. http://www.aspb.org/ http://www.asbmb.org/ASBMB/site.nsf http://www.ncbi.nih.gov/entrez/query.fcgi |
The oxidation of fatty acids in peroxisomes creates superoxide and
hydroxyl radicals as well as hydrogen peroxide. All of these Reactive
Oxygen Species (ROS) can damage proteins and nucleic acids in cells.
This damage is prevented to some extent by enzymes within peroxisomes
such as superoxide dismutase, catalase, ascorbate peroxidase, and
thioredoxin peroxidase that scavenge and detoxify the ROS. Graduate
students in the laboratory have been investigating the protective
functions of some of these enzymes. For example, Tulin Olcum-Yanik,
who completed her PhD in 2002, investigated the idea that catalase
is physically associated with another protein that is contained
in peroxisomes in a way that shields that protein from oxidative
damage by hydrogen peroxide. Dina Karyotou’s PhD project concerned
ascorbate peroxidase that is associated with the peroxisomal membrane
and can scavenge smaller concentrations of hydrogen peroxide than
catalase. This peroxidase is situated to prevent the escape of hydrogen
peroxide from the peroxisome.|
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