ZFIN ID: ZDB-PERS-150729-1
Chan, Sherine
Email: chans@musc.edu
URL: http://www.sherinechan.com
Affiliation: Sherine Chan Lab
Address: Department of Drug Discovery and Biomedical Sciences Medical University of South Carolina 280 Calhoun St, QF207 Charleston, SC 29425
Country: United States
Phone: 843-792-6095
Fax: 843-792-8436
ORCID ID:


BIOGRAPHY AND 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.


PUBLICATIONS
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

NON-ZEBRAFISH PUBLICATIONS
Bohovych I, Chan SSL, Khalimonchuk O. Mitochondrial protein quality control: the mechanisms guarding mitochondrial health. 2015. Antioxidants and Redox Signaling, 145(1):108-17. PMCID: PMC4408963.

Whitaker RM, Stallons LJ, Kneff JE, Harmon JL, Rahn JJ, Arthur JM, Beeson CC, Chan SSL and Schnellmann RG. Urinary mitochondrial DNA predicts progression of renal dysfunction and mitochondrial disruption in acute kidney injury. Kidney International. 2015. In Press.

Zhang L*, Chan SSL*, Wolff D. Mitochondrial Disorders of DNA Polymerase γ Dysfunction: From Anatomic to Molecular Pathology Diagnosis. 2011. Archives of Pathology and Laboratory Medicine. * co-first authors. PMCID: PMC3158670.

Chan SSL, Copeland WC. Functional assessment of mutant mitochondrial DNA polymerase proteins involved in human disease. 2009. Methods in Molecular Biology, 554:59-72. PMCID: PMC2886993

Chan SSL, Naviaux RK, Basinger AA, Casas KA, Copeland WC. De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome. 2009. Mitochondrion, 9(5):340-345. PMCID: PMC2748142

Kasiviswanathan R, Longley MJ, Chan SSL, Copeland WC. Disease mutations in the human mitochondrial DNA polymerase thumb subdomain impart severe defects in mtDNA replication. 2009. Journal of Biological Chemistry, 284(29):19501-19510. PMCID: PMC2740576

Chan SSL, Copeland WC. DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations. 2009. Biochimica et Biophysica Acta – Bioenergetics, 1787(5):312-319. PMCID: PMC2742478

Chan SSL, Santos JH, Meyer JN, Mandavilli BS, Cook Jr DL, McCash CL, Kissling G, Nyska A, Foley JF, van Houten B, Copeland WC, Walker VE, Witt, KL, Bishop JB. Mitochondrial toxicity in hearts of CD-1 mice following perinatal exposure to AZT, 3TC, or AZT/3TC in combination. 2007. Environmental and Molecular Mutagenesis, 48(3-4):190-200.

Lewis W, Day BJ, Kohler JJ, Hosseini SH, Chan SSL, Green E, Haase CP, Keebaugh E, Long R, Ludaway T, Russ R, Steltzer J, Tioleco N, Santoianni R, Copeland WC. Mitochondrial DNA depletion, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase gamma. 2007. Laboratory Investigation, 87(4):318-325. PMCID: PMC1831462

Nguyen KV, Sharief FS, Chan SSL, Copeland WC, Naviaux RK. Molecular diagnosis of Alpers syndrome. 2006. Journal of Hepatology. 45(1):108-116.

Chan SSL, Longley MJ, Copeland WC. Modulation of the W748S mutation in DNA polymerase gamma by the E1143G polymorphism in mitochondrial disorders. 2006. Human Molecular Genetics, 15(23):3473-3483. PMCID: PMC1780027

Chan SSL, Longley MJ, Copeland WC. A common A467T mutation in POLG compromises catalytic efficiency and interaction with the accessory subunit in mitochondrial DNA polymerase. 2005. Journal of Biological Chemistry, 280(36):31341-31346.

Chan SSL, Longley MJ, Naviaux RK, Copeland WC. Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers Syndrome. 2005. DNA Repair, 4(12):1381-1389.

Chan SSL, Kent GN, Will RK. A sensitive assay for the measurement of serum chondroitin sulfate 3B3(-) epitope levels in human rheumatic diseases. Clinical and Experimental Rheumatology. 2001. 19(5):533-540.