Education

Ph.D., Massachusetts Institute of Technology, 1996

Lab information

Rouault Lab

Research focus

Iron-related human diseases

Publications

• Tong W-H, Ollivierre H, Noguchi A, Ghosh MC, Springer DA, Rouault TA. “Hyperactivation of mTOR and AKT in A Cardiac Hypertrophy Animal Model of Friedreich Ataxia” Heyron, 2022 8(8): e10371.
• Liu G, Sil D, Tong W-H. Maio N, Bollinger J.M. Krebs C. Rouault TA. “Dependence of heme biosynthesis on iron-sulfur cluster biogenesis: human ALAD is an unregognized iron-sulfur protein” Nat Comm. 2020 11(1):6310. PMID: 33298951
• Tong W-H, Maio N, Zhang DL, Palmieri EM, Ollivierre H, Ghosh MC, McVicar DW, Rouault TA. “TLR-activated repression of Fe-S cluster biogenesis drives a metabolic shift and alters histone and tubulin acetylation“ Blood Advance 2018, 2(10):1146-1156. PMID: 29784770
• Maio N, Singh A, Uhrigshardt H, Saxena N, Tong W-H, Rouault TA. “Cochaperone binding to LYR motifs confers specificity of iron sulfur cluster delivery.” Cell Metabolism. 2014, 19:445-57.
• Crooks DR, Natarajan TG, Jeong SY, Chen C, Park SY, Huang H, Ghosh MC, Tong W-H, Haller RG, Wu C, Rouault TA. “Elevated FGF21 secretion, PGC-1α and ketogenic enzyme expression are hallmarks of iron-sulfur cluster depletion in human skeletal muscle.” Hum. Mol. Genet. 2014, ;23(1):24-39.
• Ghosh MC, Zhang DL, Jeong SY, Kovtunovych G, Ollivierre-Wilson H, Noguchi A, Tu T, Senecal T, Robinson G, Crooks DR, Tong W-H, Ramaswamy K, Singh A, Graham BB, Tuder RM, Yu ZX, Eckhaus M, Lee J, Springer DA, Rouault TA. “Deletion of iron regulatory protein 1 causes polycythemia and pulmonary hypertension in mice through translational derepression of HIF2α.” Cell Metab. 2013, 17(2):271-81.
• Crooks DR, Jeong SY, Tong W-H, Ghosh MC, Olivierre H, Haller RG, Rouault TA. “Tissue specificity of a human mitochondrial disease: differentiation-enhanced mis-splicing of the Fe-S scaffold ISCU renders patient cells more sensitive to oxidative stress in ISCU myopathy.” J. Biol. Chem. 2012, 287(48):40119-30.
• Cameron, J.M., Janer, A., Levandovskiy, V., Mackay, N., Rouault, T.A., Tong W-H., Ogilvie, I., Shoubridge, E.A., Robinson, B.H. "Mutations in Iron-Sulfur Cluster Scaffold Genes NFU1 and BOLA3 Cause a Fatal Deficiency of Multiple Respiratory Chain and 2-Oxoacid Dehydrogenase Enzymes." Am. J. Hum. Genet. 2011, 89(4):486-95.
• Tong W-H., Sourbier C, Kovtunovych G, Jeong SY, Vira M, Ghosh, M, Valera-Romero V, Sougrat S, Vaulont S, Viollet B, Kim YS, Lee S, Trepel J, Srinivasan R, Bratslavsky G, Yang Y, Linehan WM & Rouault TA "The glycolytic shift in fumarate- hydratase-deficient kidney cancer lowers AMPK levels, increased anabolic propensities and lowers cellular iron levels" Cancer Cell 2011, 20: 315-327.
• Bullock GC, Delehanty LL, Talbot A-L, Gonias SL, Tong W-H., Rouault TA, Dewar B, Macdonald JM, Chruma JJ, Goldfarb AN "Iron and Isocitrate Calibrate Erythropoietin Responsiveness of Erythroid Progenitors Via *Aconitase* Tuning of Protein Kinase C Activity" Blood 2010, 114(22): 260-260.
• Crooks DR, Ghosh MC, Haller RG, Tong W-H, Rouault TA. "Post-translational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery." Blood 2010, 115(4) 860-869.
• Shi Y, Ghosh M, Tong W-H, Rouault T.A. "Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis" Hum Mol Genet. 2009, 18 (16): 3014-3025
• Ghosh, M.C., Tong, W.-H., Zhang, D., Ollivierre-Wilson, H., Singh, A., Krishna, M.C., Mitchell, J.B., Rouault, T.A. "Tempol- mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice" Proc. Nat. Acad. Sci. 2008, 105, 12028-12033.
• Mochel, F. Knight, M.A., Tong, W.-H., Hernandez, D., Ayyad, K., Taivassalo, T., Andersen P.M., Singleton, A., Rouault, T.A., Fischbeck, K.H., Haller, R.G. "Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance." Am. J. Hum. Genet. 2008, 82, 652-60.
• Li, K., Tong, W.-H., Hughes, R.M., and Rouault, T.A. "Roles of the mammalian cytosolic cysteine desulfurase, ISCSs, and scaffold protein, ISCU in iron-sulfur cluster assembly." J. Biol. Chem. 2006, 281, 12344-51.
• Tong, W,-H., and Rouault, T.A. "Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis." Cell Metabolism, 2006, 3, 199-210.
• Smith, S.R., Ghosh, M.C., Ollivierre-Wilson, H., Tong, W,-H., and Rouault, T.A. "Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development." Blood Cells Mol. Dis. 2006, 36, 283-7.
• Tong, W.-H., Jameson, G.N., Huynh, B.H., Rouault, T.A. “Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its ability to assemble a [4Fe-4S] cluster.” Proc. Natl. Acad. Sci. U S A. 2003, 100, 9762-9767.
• Tong, W.-H., Rouault, TA. “Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells” EMBO J. 2000, 19, 5692-5700.
• Tong, W.-H., Burdi, D., Riggs-Gelasco, P., Chen, S., Edmondson, D., Huynh, B.H., Stubbe, J., Han, S., Arvai, A., Tainer, J.. "Characterization of Y122F R2 of Escherichia coli ribonucleotide reductase by time-resolved physical biochemical methods and X-ray crystallography" Biochemistry 1998, 37, 5840-5848.
• Sturgeon, B.E., Doan, P.E., Liu, K.E., Burdi, D., Tong, W.-H., Nocek, J.M., Gupta, N., Stubbe, J., Kurtz, D.M., Lippard, S.J., Hoffman, B.M. "Non-Kramers ESEEM of integer-spin diferrous carboxylate-bridged clusters in proteins" J. Am. Chem. Soc. 1997, 119, 375-386.
• Tong, W.-H., Chen, S., Lloyd, S. G., Edmondson, D. E., Huynh, B. H., Stubbe, J. "Mechanism of assembly of the diferric cluster-tyrosyl radical cofactor of Escherichia coli ribonucleotide reductase from the diferrous form of the R2 subunit" J. Amer. Chem. Soc. 1996, 118, 2107-2108.
• Burdi, D., Sturgeon, B. E., Tong, W.-H., Stubbe, J., Hoffman, B. M. "Rapid-freeze quench ENDOR of the radical X intermediate of Escherichia coli ribonucleotide reductase using 17O2, H217O, and 2H2O" J. Am. Chem. Soc. 1996, 118, 281-282.
• Pulver, S. C., Tong, W.-H., Bollinger, J. M., Stubbe, J., Solomon, E. I. "Circular dichroism and magnetic circular dichroism studies of the fully reduced binuclear non-heme iron active site in the Escherichia coli R2 subunit of ribonucleoside diphosphate reductase" J. Am. Chem. Soc. 1995, 117, 12664-12678.
• Bollinger, J. M., Jr., Tong, W.-H., Ravi, N., Huynh, B. H., Edmondson, D. E., Stubbe, J. "Mechanism of assembly of the tyrosyl radical-diiron(III) cofactor of E. coli ribonucleotide reductase: II. Kinetics of the excess Fe2+ reaction by optical, EPR and Mossbauer spectroscopies" J. Am. Chem. Soc. 1994, 116, 8015-8023.
• Bollinger, J. M., Jr., Tong, W.-H., Ravi, N., Huynh, B. H., Edmondson, D. E., Stubbe, J. "Mechanism of assembly of the tyrosyl radical-diiron(III) cofactor of E. coli ribonucleotide reductase: III. Kinetics of the limiting Fe2+ reaction by optical, EPR and Mossbauer spectroscopies" J. Am. Chem. Soc. 1994, 116, 8024.

Review Articles and Book Chapters

• Tong W-H. “Iron-sulfur proteins and human diseases.” in Iron-sulfur cluster in chemistry and biology, T.A. Rouault, Editor. 2017, De Gruyter: Berlin. Vol. 2 p. 227-318.
• Holmes-Hampton GP, Tong W-H, Rouault TA. “Biochemical and biophysical methods for studying mitochondrial iron metabolism.” Methods Enzymol. 2014, 547:275-307. PMID: 25416363
• Tong W-H. “Iron-sulfur proteins and human diseases.” in Iron-sulfur cluster in chemistry and biology, T.A. Rouault, Editor 2014, De Gruyter: Berlin. p. 455-512.
• Rouault, TA; Tong, W-H "Tangled Up In Red: Intertwining of the Heme and Iron-Sulfur Cluster Biogenesis Pathways"
• Cell Metabolism 2009, 10 (2): 80-81.
• Rouault, T.A. and Tong, W.-H. " Iron-sulfur cluster biosynthesis and human disease." Trends Genet. 2008, 4, 398-407.
• Tong, W,-H., and Rouault, T.A. "Metabolic regulation of citrate and iron by aconitases: role of iron-sulfur cluster biogenesis." Biometals, 2007, 20, 549-64.
• Rouault, T.A. and Tong, W.-H. " Iron-sulfur cluster biosynthesis and mitochondrial iron homeostasis." Nat. Rev. Mol. Cell Biol. 2005, 6, 341-351
• Bollinger, J. M., Jr., Tong, W.-H., Ravi, N., Huynh, B. H., Edmondson, D. E., Stubbe, J. "Use of rapid kinetics methods to study the assembly of the diferric-tyrosyl radical cofactor of E. coli ribonucleotide reductase" Methods Enzymol. 1996, 258, 278-303.