Positions

Director, Center for Mitochondrial Genetics and Health

Assistant Director for Greater Bay Area Institute of Precision Medicine (Guangzhou)

Distinguished Professor, Fudan University

Courtesy Professor, Cornell University

Research Direction

A. mtDNA mutation dynamics

A1. Environmental factors affecting mtDNA mutations

A2. Somatic: mtDNA mutation dynamics and diseases

A3. Germ line mtDNA dynamics and children diseases

A4. Population: mtDNA variation and environmental adaptation; mtDNA and nDNA interaction

A5. Cell free mtDNA secretion and mutations
B. Consequences of mtDNA mutation
The impact of mtDNA mutation/mitochondrial functional stress on inflammation/immunity, histone modification and epegenetics, genome instability, and stem cell differentiation
C. Solution to reducing mtDNA mutation
Exercise physiology
Functional food component/Chinese medicine screening
Mitophagy/lysosomal biology

Accomplishment

1. Evolution of duplicate genes

2. Single cell mtDNA mutation dynamics;

3. mtDNA mutations and disease association

4. Distribution of mtDNA heteroplasmy in healthy and disease populations

1998, BS, Peking University

2003, PhD, University of Chicago

2004-2006, Postdoc Stanford University

2006-2020, Assistant/Associate/Full Professor, Cornell University

2011, Future Leader in Nutrition Award

Associate Editor, Nutrition and Metabolism

Associate Editor, Mitochondrial Communication

1. Kang W, Barad A, Clark AG, Wang Y, Lin X, Gu Z, O'Brien KO.Ethnic Differences in Iron Status.Adv Nutr. 2021 Oct 1;12(5):1838-1853. doi: 10.1093/advances/nmab035.PMID:34009254  

2. Wang X, An P, Gu Z, Luo Y, Luo J.Mitochondrial Metal Ion Transport in Cell Metabolism and Disease.Int J Mol Sci. 2021 Jul 14;22(14):7525. doi: 10.3390/ijms22147525.PMID: 34299144 

3. Wang Y, Guo X, Ye K, Orth M, Gu Z.Accelerated expansion of pathogenic mitochondrial DNA heteroplasmies in Huntington's disease.PNAS 2021 Jul 27;118(30):e2014610118. doi:10.1073/pnas.2014610118.PMID: 34301881 

4. Tang J, Liu J, Yan Q, Gu Z, August A, Huang W, Jiang Z.Konjac Glucomannan Oligosaccharides Prevent Intestinal Inflammation Through SIGNR1-Mediated Regulation of Alternatively Activated Macrophages.Mol Nutr Food Res. 2021 Oct;65(20):e2001010. doi: 10.1002/mnfr.202001010. Epub 2021 Aug 25.PMID: 34390195

5. Wu J, Lin D, Jiu L, Liu Q, Gu Z, Luo J, Zhao Y.Exploring epigenetic biomarkers of universal specificities and commonalities among pan-cancer cohorts in The Cancer Genome Atlas.Epigenomics. 2021 Apr;13(8):599-612. doi: 10.2217/epi-2021-0050. Epub 2021 Mar 31.PMID: 33787302

6. Wang Y, Wang X, Long Q, Liu Y, Yin T, Sirota I, Ren F, Gu Z, Luo J.Reducing embryonic mtDNA copy number alters epigenetic profile of key hepatic lipolytic genes and causes abnormal lipid accumulation in adult mice.FEBS J. 2021 Dec;288(23):6828-6843. doi: 10.1111/febs.16121. Epub 2021 Jul 30.PMID: 34258867

7. Chen H, Blum JE, Thalacker-Mercer A, Gu Z.Impact of the Whole Genome Duplication Event on PYK Activity and Effects of a PYK1 Mutation on Metabolism in S. cerevisiae.Front Mol Biosci. 2021 Mar 16;8:656461. doi: 10.3389/fmolb.2021.656461. eCollection 2021.PMID: 33796550 

8. Lin D, Wang R, Luo J, Ren F, Gu Z, Zhao Y, Zhao L. The Core and Distinction of the Gut Microbiota in Chinese Populations across Geography and Ethnicity. Microorganisms. 2020 Oct 14;8(10):1579. doi: 10.3390/microorganisms8101579. PMID: 33066420; PMCID: PMC7602275.

9.  Guo X, Wang Y, Zhang R, Gu Z. STAMP: a multiplex sequencing method for simultaneous evaluation of mitochondrial DNA heteroplasmies and content. NAR Genom Bioinform. 2020 Dec;2(4):lqaa065. doi: 10.1093/nargab/lqaa065. Epub 2020 Oct 19. PMID: 33134911; PMCID: PMC7573736.

10.  Guo X, Zhang R, Li Y, Wang Z, Ishchuk OP, Ahmad KM, Wee J, Piskur J, Shapiro JA, Gu Z. Understand the genomic diversity and evolution of fungal pathogen Candida glabrata by genome-wide analysis of genetic variations. Methods. 2020 Apr 1;176:82-90. doi: 10.1016/j.ymeth.2019.05.002. Epub 2019 May 3. PMID: 31059831.

11. Liu Q, Yang X, Long G, Hu Y, Gu Z, Boisclair YR, Long Q. ERAD deficiency promotes mitochondrial dysfunction and transcriptional rewiring in human hepatic cells. J Biol Chem. 2020 Dec 4;295(49):16743-16753. doi: 10.1074/jbc.RA120.013987. Epub 2020 Sep 25. PMID: 32978261.

12. Wang X, Yang S, Li S, Zhao L, Hao Y, Qin J, Zhang L, Zhang C, Bian W, Zuo L, Gao X, Zhu B, Lei XG, Gu Z, Cui W, Xu X, Li Z, Zhu B, Li Y, Chen S, Guo H, Zhang H, Sun J, Zhang M, Hui Y, Zhang X, Liu X, Sun B, Wang L, Qiu Q, Zhang Y, Li X, Liu W, Xue R, Wu H, Shao D, Li J, Zhou Y, Li S, Yang R, Pedersen OB, Yu Z, Ehrlich SD, Ren F. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents. Gut. 2020 Dec;69(12):2131-2142. doi: 10.1136/gutjnl-2019-319766. Epub 2020 Apr 2. PMID: 32241904; PMCID: PMC7677483.

13.  Wang Z, Sun X, Wee J, Guo X, Gu Z. Novel insights into global translational regulation through Pumilio family RNA-binding protein Puf3p revealed by ribosomal profiling. Curr Genet. 2019 Feb;65(1):201-212. doi: 10.1007/s00294-018-0862-4. Epub 2018 Jun 27. PMID: 29951697; PMCID: PMC6666313.

14. Kraja AT, Liu C, Fetterman JL, Graff M, Have CT, Gu C, Yanek LR, Feitosa MF, Arking DE, Chasman DI, Young K, Ligthart S, Hill WD, Weiss S, Luan J, Giulianini F, Li-Gao R, Hartwig FP, Lin SJ, Wang L, Richardson TG, Yao J, Fernandez EP, Ghanbari M, Wojczynski MK, Lee WJ, Argos M, Armasu SM, Barve RA, Ryan KA, An P, Baranski TJ, Bielinski SJ, Bowden DW, Broeckel U, Christensen K, Chu AY, Corley J, Cox SR, Uitterlinden AG, Rivadeneira F, Cropp CD, Daw EW, van Heemst D, de Las Fuentes L, Gao H, Tzoulaki I, Ahluwalia TS, de Mutsert R, Emery LS, Erzurumluoglu AM, Perry JA, Fu M, Forouhi NG, Gu Z, Hai Y, Harris SE, Hemani G, Hunt SC, Irvin MR, Jonsson AE, Justice AE, Kerrison ND, Larson NB, Lin KH, Love-Gregory LD, Mathias RA, Lee JH, Nauck M, Noordam R, Ong KK, Pankow J, Patki A, Pattie A, Petersmann A, Qi Q, Ribel-Madsen R, Rohde R, Sandow K, Schnurr TM, Sofer T, Starr JM, Taylor AM, Teumer A, Timpson NJ, de Haan HG, Wang Y, Weeke PE, Williams C, Wu H, Yang W, Zeng D, Witte DR, Weir BS, Wareham NJ, Vestergaard H, Turner ST, Torp-Pedersen C, Stergiakouli E, Sheu WH, Rosendaal FR, Ikram MA, Franco OH, Ridker PM, Perls TT, Pedersen O, Nohr EA, Newman AB, Linneberg A, Langenberg C, Kilpeläinen TO, Kardia SLR, Jørgensen ME, Jørgensen T, Sørensen TIA, Homuth G, Hansen T, Goodarzi MO, Deary IJ, Christensen C, Chen YI, Chakravarti A, Brandslund I, Bonnelykke K, Taylor KD, Wilson JG, Rodriguez S, Davies G, Horta BL, Thyagarajan B, Rao DC, Grarup N, Davila-Roman VG, Hudson G, Guo X, Arnett DK, Hayward C, Vaidya D, Mook-Kanamori DO, Tiwari HK, Levy D, Loos RJF, Dehghan A, Elliott P, Malik AN, Scott RA, Becker DM, de Andrade M, Province MA, Meigs JB, Rotter JI, North KE. Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits. Am J Hum Genet. 2019 Jan 3;104(1):112-138. doi: 10.1016/j.ajhg.2018.12.001. Epub 2018 Dec 27. PMID: 30595373; PMCID: PMC6323610.

15.  Yang X, Zhang R, Nakahira K, Gu Z. Mitochondrial DNA Mutation, Diseases, and Nutrient-Regulated Mitophagy. Annu Rev Nutr. 2019 Aug 21;39:201-226. doi: 10.1146/annurev-nutr-082018-124643. PMID: 31433742.

16.  Zhang R, Nakahira K, Choi AMK, Gu Z. Heteroplasmy concordance between mitochondrial DNA and RNA. Sci Rep. 2019 Sep 10;9(1):12942. doi: 10.1038/s41598-019-49279-7. PMID: 31506522; PMCID: PMC6737107.

17.  Trumpff C, Marsland AL, Basualto-Alarcón C, Martin JL, Carroll JE, Sturm G, Vincent AE, Mosharov EV, Gu Z, Kaufman BA, Picard M. Acute psychological stress increases serum circulating cell-free mitochondrial DNA. Psychoneuroendocrinology. 2019 Aug;106:268-276. doi: 10.1016/j.psyneuen.2019.03.026. Epub 2019 Mar 28. PMID: 31029929; PMCID: PMC6589121.

18.  Liu Q, Lin D, Li M, Gu Z, Zhao Y. Evidence of Neutral Evolution of Mitochondrial DNA in Human Hepatocellular Carcinoma. Genome Biol Evol. 2019 Oct 1;11(10):2909-2916. doi: 10.1093/gbe/evz214. PMID: 31599941; PMCID: PMC6804334.

19.  Tiukova IA, Jiang H, Dainat J, Hoeppner MP, Lantz H, Piskur J, Sandgren M, Nielsen J, Gu Z, Passoth V. Assembly and Analysis of the Genome Sequence of the Yeast Brettanomyces naardenensis CBS 7540. Microorganisms. 2019 Oct 26;7(11):489. doi: 10.3390/microorganisms7110489. PMID: 31717754; PMCID: PMC6921048.

20.  Si Y, Liu X, Ye K, Bonfini A, Hu XY, Buchon N, Gu Z. Glucomannan Hydrolysate Promotes Gut Proliferative Homeostasis and Extends Life Span in Drosophila melanogaster. J Gerontol A Biol Sci Med Sci. 2019 Sep 15;74(10):1549-1556. doi: 10.1093/gerona/gly189. PMID: 30252027; PMCID: PMC6748797.

21.  Kothapalli KSD, Park HG, Guo X, Sun X, Zou J, Hyon SS, Qin X, Lawrence P, Ran-Ressler RR, Zhang JY, Gu Z, Brenna JT. A novel FADS2 isoform identified in human milk fat globule suppresses FADS2 mediated Δ6-desaturation of omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids. 2018 Nov;138:52-59. doi: 10.1016/j.plefa.2018.06.004. Epub 2018 Jun 28. PMID: 30041907; PMCID: PMC6218299.

22.  Zhang, R., Wang, Y., Ye, K., Picard, M., Gu, Z. Aging is Independently Associated with Mitochondrial DNA Quality and Quantity in Humans. 2017, BMC Genomics. 18(1):890.

23. Cheng, J., Guo, X., Cai, P., Cheng, X., Piskur, J., Ma, Y., Jiang, H. & Gu, Z. Parallel Evolution of Chromatin Structure Underlying Metabolic Adaptation. Molecular Biology and Evolution, 2017, 34(11):2870-2878.

24. Wang J, Zou H, Chen L, Long X, Lan J, Liu W, Ma L, Wang C, Xu X, Ren L, Gu Z, Li N, Hu X, Zhao Y, Zhao Y. Convergent and divergent genetic changes in the genome of Chinese and European pigs. Sci Rep. 2017 Aug 17;7(1):8662.

25. Hanson MR, Gu Z, Keinan A, Ye K, Germain A, Billing-Ross P. Association of mitochondrial DNA variants with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms. J Transl Med. 2016 Dec 20;14(1):342.

26. Wang Y, Picard M, & Gu Z. Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder. PLoS Genetics. 2016; 12(10):e1006391. PMID: 27792786 PMCID: PMC5085253.

27. Billing-Ross P, Germain A, Ye K, Keinan A, Gu Z & Hanson MR. Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome. Journal of Translational Medicine. 2016; 14:19. PMID: 26791940 PMCID: PMC4719218

28. Zhang R, Nakahira K, Guo X, Choi AM, & Gu Z. Very Short Mitochondrial DNA Fragments and Heteroplasmy in Human Plasma. Scientific Reports. 2016; 6:36097. PMID: 27811968 PMCID: PMC5095883.

29. Kothapalli, K.S., Ye, K., Gadgil, M.S., Carlson, S.E., O'Brien, K.O., Zhang, J.Y., Park, H.G., Ojukwu, K., Zou, J., Hyon, S.S., Joshi, K.S., Gu, Z., Keinan, A. & Brenna, J.T. Positive Selection on a Regulatory Insertion-Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid. Mol Biol Evol. 33(7):1726-1739 (2016). PMCID:PMC4915354

30. Sun, X., Wang, Z., Guo, X., Li, H. & Gu, Z. Coordinated Evolution of Transcriptional and Post-Transcriptional Regulation for Mitochondrial Functions in Yeast Strains. PLoS ONE. 11(4):e0153523 (2016). PMCID: PMC4831757

31. Barker B, Xu L, Gu Z. Dynamic Epistasis under Varying Environmental Perturbations. PLoS ONE. 2015 Jan 27;10(1):e0114911. doi: 10.1371/journal.pone.0114911. eCollection 2015.

32. Lei R, Ye K, Gu Z, Sun X. Diminishing returns in next-generation sequencing (NGS) transcriptome data. Gene. 2015 Feb 15;557(1):82-7.

33. Jiang H, Xu L, Wang Z, Keene J, Gu Z. Coordinating expression of RNA binding proteins with their mRNA targets. Sci Rep. 2014 Nov 24;4:7175.

34. Ye K, Lu J, Ma F, Keinan A, Gu Z. Reply to Just et al.: Mitochondrial DNA heteroplasmy could be reliably detected with massively parallel sequencing technologies. Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):E4548-50.

35. Ye K, Lu J, Ma F, Keinan A, Gu Z. Extensive pathogenicity of mitochondrial heteroplasmy in healthy human individuals. Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10654-9

36. Ahmad KM, Kokošar J, Guo X, Gu Z, Ishchuk OP, Piškur J. Genome structure and dynamics of the yeast pathogen Candida glabrata. FEMS Yeast Res. 2014 Jun;14(4):529-35.

37. Liu, X., Jiang, H., Gu, Z. & Roberts, J.W. High-resolution view of bacteriophage lambda gene expression by ribosome profiling. Proc Natl Acad Sci U S A. 110:11928-11933 (2013)

38. Shestov, A.A., Barker, B., Gu, Z. & Locasale JW  Computational approaches for understanding energy metabolism. Wiley Interdiscip Rev Syst Biol Med. doi: 10.1002/wsbm.1238, (2013)

39. Ye, K. Lu, J., Madhura Raj, S. & Gu, Z. Human expression QTLs are enriched in signals of environmental adaptation , Genome Biol Evol. 5:1689-1701 (2013)

40. Xu, L., Barker, B. & Gu, Z. Dynamic epistasis for the different alleles of the same gene, PNAS, 109:10420-10425 (2012)

41. Jiang, H., Guo, X., Xu, L. & Gu, Z. Rewiring of post-transcriptional RNA regulons: Puf4p in fungi as an example, Mol Biol Evol. 29:2169-2176 (2012)

42. Stover, P. & Gu, Z.  Polymorphism: effect on nutrient utilization and metabolism.  Book Chapter,  Modern Nutrition in Health and Diseases, (2011)

43. Ye, K. & Gu, Z. Recent advances in understanding the role of nutrition in genome evolution, Advances in Nutrition, 2:486-496, (2011)

44. Xue, Z., He, Y., Ye, K., Gu, Z., Mao, Y. & Qi, L. A highly-conserved structural “hinge” bridging the kinase and RNase domains of the IRE1 protein is critical for its stability and activation. J Biol Chem 286:30859-30866 (2011)

45. Xu, L, Jiang, H & Gu,  Z. Genetic architecture of complex traits revealed by epistatic interaction. In press, Genome Biol. & Evol. 3:909-914 (2011)

46. Zou, Y., Huang, W., Gu, Z. & Gu, X. Predominant gain of promoter TATA box after gene duplication associated with stress responses. Mol Biol Evol. 28:2893-2904 (2011)

47. Jiang, H. Xu, L & Gu, Z. Growth of novel epistatic interaction by gene duplication,  Genome Biol & Evol, 3:295-301 (2011)

48. Xu, L. & Gu, Z. Asynchronous regulation of backup circuits as a strategy for survival in the fluctuating environments. International Journal of Systems and Synthetic Biology, 1: 227-239 (2010)

49. K.T. Nishant , Wei, W., Mancera, E., Argueso, J.L., Schlattl, A., Delhomme, N., Ma, X., Bustamante, C., Korbel, J., Gu, Z., Steinmetz, L., Alani, E.  The baker's yeast diploid genome is remarkably stable in vegetative growth and meiosis, PLoS Genetics 6(9): e1001109 (2010)

50. Zanders, S., Ma, X., RoyChoudhury, A., Hernandez, R., Demogines, A., Barker, B., Indap, A., Gu, Z., Bustamante, C.,  & Alani, E. Detection of heterozygous mutations in the genome of mismatch repair defective diploid yeast using a Bayesian approach. Genetics 186:493-503 (2010)

51. Jiang, H., Guan, W. & Gu, Z. Tinkering evolution of a posttranscriptional RNA regulon by Puf3p in yeast. PLoS Genetics 6(7): e1001030 (2010)

52. Guan, W., Jiang, H., Xu, L., Li, Y., Steinmetz, L.M., Li, Y. & Gu, Z. Antagonistic changes in sensitivity to antifungal drugs by functional loss of an important ABC transporter gene. PLoS ONE 5(6): e11309 (2010)

53. Li, Y., Liang, H., Gu, Z., Lin, Z., Guan, L., Zhou, L., Li, Y. & Li, W.-H. Detecting positive selection in the budding yeast genome, J . Evol. Bio. 22:2430-2437 (2009)

54. Gu, Z. & Oliver, S.G. Yeasts as models in evolutionary biology. Genome Biology 10:304 (2009)

55. Xu, L., Su, Z. Gu, Z. & Gu, X. Parallel adaptation vs. mutation hotspot for the evolution of RNases in leaf monkeys. Mol. Phyl. & Evol. 50:397-400 (2009)

56. Jiang, H., Wang, W. & Gu, Z. Genetic diversities detected by translational efficiency between Ashbya gossypii and yeasts. BMC Evol Biol. 8:343 (2008)

57. Chen, H., Xu, L. & Gu, Z. Regulation dynamics of the WGD genes during the yeast metabolic oscillation. Mol. Biol. & Evol 25:2513-2516 (2008)

58. Jiang, H, Guan, W., Pinney, D., Wang, W. & Gu, Z. Functional relaxation of mitochondria after WGD in yeast. Genome Res. 18:1466-1471 (2008)

59. Wu, W., McCusker, J.H. …Gu, Z. ... Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789. P. Natl. Acad. Sci. USA. 104:12825-12830
(2007)

60. Jiang, H., Liu, D., Gu, Z. & Wang, W. Rapid evolution in a pair of recent duplicate segments of rice. Exp Zoolog B Mol Dev Evol. 308:50-57 (2007)

61. Oakley, T. H., Gu, Z., Abouheif, E., Patel, N. H. & Li, W.-H. Comparative analyses of gene expression evolution using functional genomic data. Mol. Biol. & Evol. 22:40-50 (2005)

62. Maltsev, N., Glass, E.M., Ovchinnikova, G., Gu, Z. Molecular mechanisms involved in robustness of yeast central metabolism against null mutations. J Biochem. (Tokyo) 137:177-187 (2005)

63. Gu, Z., David, L., Petrov, D., Jones, T., Davis, R. W. & Steinmetz, L. M.  Elevated evolutionary rates in the lab strain of S. cerevisiae.  P. Natl. Acad. Sci. USA. 102:1092-1097 (2005)

64. Gu, Z., Rifkin, S.A., White, K. P. & Li, W.-H. Duplicate genes increase expression diversity within and between species. Nat. Genet. 36:577 - 579 (2004)

65. Marland, E., Prachumwat, A., Maltsev, N., Gu, Z. & Li, W.-H. Higher gene duplicabilities for metabolic proteins than for nonmetabolic proteins in yeast and E. coli. J Mol Evol. 59:806-814 (2004)

66. Zhang, P, Gu, Z. & Li, W-H. Different evolutionary patterns between young duplicate genes in the human genome. Genome Biology 4:R56 (2003)

67. Yang, J., Gu, Z. & Li, W.-H. Rate of evolution vs. fitness effect of gene deletion. Mol. Biol. & Evol. 20:772-774 (2003)

68. Cavalcanti, A., Ferreira, R., Gu, Z. & Li, W.-H. Patterns of gene duplication in yeast and C. elegans. J Mol. Evol. 56:28-37 (2003)

69. Li, W.-H., Gu, Z., Cavalcanti, A.& Nekrutenko, A. Detection of gene duplications and block duplications in eukaryotic genomes. J Str. & Funct. Genom. 3:27-34 (2003)

70. Gu, Z., Steinmetz, L. M., Gu, X., Scharfe, C., Davis, R. W., & Li, W.-H. Role of duplicate genes in genetic robustness against null mutations. Nature 421:63-66 (2003)

71. Gu, Z., Nicolae, D., Lu, H.-S., & Li, W.-H. Rapid divergence in expression between duplicate genes inferred from microarray gene expression data. Trends Genet. 18:609-613 (2002)

72. Gu, Z., Cavalcanti, A., Chen, F.-C., Bouman, P. & Li, W.-H. Extent of gene duplication in the genomes of drosophila, nematode, and yeast. Mol. Biol. & Evol. 19:256-262 (2002)

73. Li, W.-H., Gu, Z., Wang, H. & Nekrutenko, A. Evolutionary analyses of the human genome. Nature 409:847-849 (2001)