ZFIN ID: ZDB-LAB-150729-1
Sherine Chan Lab
PI/Director: Chan, Sherine
Contact Person: Chan, Sherine
Email: chans@musc.edu
URL: http://www.sherinechan.com
Address: Department of Drug Discovery and Biomedical Sciences Medical University of South Carolina 280 Calhoun St, QF207 Charleston, SC 29425
Country: United States
Phone: 843-792-2550
Fax: 843-792-8436
Line Designation: muz

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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.

Williamson, Tucker Graduate Student Rahn, Jennifer Research Staff Stackley, Krista Research Staff

Sharma, S., Magnitsky, S., Reesey, E., Schwartz, M., Haroon, S., Lavorato, M., Chan, S., Xiao, R., Wilkins, B.J., Martinez, D., Seiler, C., Falk, M.J. (2023) Novel Development of Magnetic Resonance Imaging to Quantify the Structural Anatomic Growth of Diverse Organs in Adult and Mutant Zebrafish. Zebrafish. 21(1):28-38
Cahill, T., Chan, S., Overton, I.M., Hardiman, G. (2023) Transcriptome Profiling Reveals Enhanced Mitochondrial Activity as a Cold Adaptive Strategy to Hypothermia in Zebrafish Muscle. Cells. 12(10):
Cahill, T., da Silveira, W.A., Renaud, L., Wang, H., Williamson, T., Chung, D., Chan, S., Overton, I., Hardiman, G. (2023) Investigating the effects of chronic low-dose radiation exposure in the liver of a hypothermic zebrafish model. Scientific Reports. 13:918918
Cahill, T., da Silveira, W.A., Renaud, L., Williamson, T., Wang, H., Chung, D., Overton, I., Chan, S.S.L., Hardiman, G. (2021) Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model. Cells. 10(4):
Li, X., Himes, R.A., Prosser, L.C., Christie, C.F., Watt, E., Edwards, S.F., Metcalf, C., West, P., Wilcox, K., Chan, S.S.L., Chou, C.J. (2020) Discovery of the first Vitamin K analog as a potential treatment of pharmacoresistant seizures. Journal of medicinal chemistry. 63(11):5865-5878
Sokol, A.M., Uszczynska-Ratajczak, B., Collins, M.M., Bazala, M., Topf, U., Lundegaard, P.R., Sugunan, S., Guenther, S., Kuenne, C., Graumann, J., Chan, S.S.L., Stainier, D.Y.R., Chacinska, A. (2019) Correction: Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish. PLoS Genetics. 15:e1007972
Sokol, A.M., Uszczynska-Ratajczak, B., Collins, M.M., Bazala, M., Topf, U., Lundegaard, P.R., Sugunan, S., Guenther, S., Kuenne, C., Graumann, J., Chan, S.S.L., Stainier, D.Y.R., Chacinska, A. (2018) Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish. PLoS Genetics. 14:e1007743
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
Rahn, J.J., Bestman, J.E., Stackley, K.D., Chan, S.S. (2015) Zebrafish lacking functional DNA polymerase gamma survive to juvenile stage, despite rapid and sustained mitochondrial DNA depletion, altered energetics and growth. Nucleic acids research. 43(21):10338-52
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
Jayasundara, N., Kozal, J.S., Arnold, M.C., Chan, S.S., Di Giulio, R.T. (2015) High-Throughput Tissue Bioenergetics Analysis Reveals Identical Metabolic Allometric Scaling for Teleost Hearts and Whole Organisms. PLoS One. 10:e0137710
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. Human molecular genetics. 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
Rahn, J.J., Stackley, K.D., and Chan, S.S. (2013) Opa1 is required for proper mitochondrial metabolism in early development. PLoS One. 8(3):e59218
Stackley, K.D., Beeson, C.C., Rahn, J.J., and Chan, S.S. (2011) Bioenergetic profiling of zebrafish embryonic development. PLoS One. 6(9):e25652