ZFIN ID: ZDB-LAB-150729-1
||Department of Drug Discovery and Biomedical Sciences
Medical University of South Carolina
280 Calhoun St, QF207
Charleston, SC 29425
GENOMIC FEATURES ORIGINATING FROM THIS LAB
all 3 genomic features
STATEMENT OF RESEARCH INTERESTS
Our mission is to understand how mitochondrial defects give rise to cellular dysfunction and disease. This is not an easy task, as the mitochondrion performs many essential functions, the most important being the production of most of the energy for the cell. Defects in any of the approximately 1,500 mitochondrial proteins can lead to pathological states such as neurodegeneration and cancer. In addition to genetic defects, mitochondrial dysfunction can arise from contact with many environmental agents and drug treatments. Mitochondria contain multiple copies of their own small, circular genome (mitochondrial DNA, mtDNA). Recently, investigators reported that 1 in 5 healthy humans harbor a pathogenic mtDNA mutation. Further complicating the understanding of mitochondrial diseases are issues related to mtDNA copy number in different tissues and different cellular states, levels of mtDNA mutations within cells (known as heteroplasmy), tissue differences in mitochondrial needs, and wide variability in disease presentation and onset of disease despite the same disease mutation.
We use several diverse in vitro and in vivo methods to analyze mitochondrial dysfunction. In particular, we are using the zebrafish as a model for mitochondrial diseases. There are no cures or effective long-term treatments for mitochondrial diseases. To fulfill our long-term goals of developing therapeutic treatments and new biomarkers for the early detection of mitochondrial disease, we are investigating pathways that are important in the development of mitochondrial disease, and the role of environmental and drug modifiers on mitochondrial function.
ZEBRAFISH PUBLICATIONS OF LAB MEMBERS
Soma, S., Latimer, A.J., Chun, H., Vicary, A.C., Timbalia, S.A., Boulet, A., Rahn, J.J., Chan, S.S.L., Leary, S.C., Kim, B.E., Gitlin, J.D., Gohil, V.M. (2018) Elesclomol restores mitochondrial function in genetic models of copper deficiency. Proceedings of the National Academy of Sciences of the United States of America. 115(32):8161-8166
Bohovych, I., Fernandez, M.R., Rahn, J.J., Stackley, K.D., Bestman, J.E., Anandhan, A., Franco, R., Claypool, S.M., Lewis, R.E., Chan, S.S., Khalimonchuk, O. (2015) Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability. Scientific Reports. 5:13989
Bestman, J.E., Stackley, K.D., Rahn, J.J., Williamson, T.J., Chan, S.S. (2015) The cellular and molecular progression of mitochondrial dysfunction induced by 2,4-dinitrophenol in developing zebrafish embryos. Differentiation; research in biological diversity. 89(3-4):51-69
Ghosh, A., Trivedi, P.P., Timbalia, S.A., Griffin, A.T., Rahn, J.J., Chan, S.S., and Gohil, V.M. (2014) Copper supplementation restores cytochrome c oxidase assembly defect in a mitochondrial disease model of COA6 deficiency. Hum. Mol. Genet.. 23(13):3596-606
Rahn, J.J., Bestman, J.E., Josey, B.J., Inks, E.S., Stackley, K.D., Rogers, C.E., Chou, C.J., and Chan, S.S. (2014) Novel Vitamin K analogs suppress seizures in zebrafish and mouse models of epilepsy. Neuroscience. 259:142-154