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Jing QU, Ph. D.

Stem Cells and Aging


Staff: Jing Qu, Yanxia Ye, Xiaoqian Liu, Ruijun Bai
Postdoc: Wenlei Bao, Xiaoqian Zhang, Qun Chu
Students: Zhiqing Diao, Zeming Wu, Xing Zhang, Hongkai Zhao, Zunpeng Liu, Huifang Hu, Zehua Wang, Shijia Bi

QU Group website

 

  Worldwide population aging is unprecedented, pervasive and enduring, with implications for many facets of human life. China’s population is also aging and shrinking. By 2040, there will be about only 1.6 workers to 1 retiree in China, and the number of Chinese older than 65 is expected to rise from roughly 130 million to more than 320 million in 2050. The consequence for China’s demographic change is profound and challenging. Meanwhile, life expectancy around the world has increased steadily. Though people are living longer, they’re also increasingly battling chronic illnesses like osteoarthritis, diabetes, heart and neurodegenerative diseases. Therefore, the health of the aging population is the most important issue to combat. If people can experience these extra years of life in good health, their ability to do the things they value will be little different from that of a younger person. Our research group is focusing on exploring the molecular targets and intervention strategies of human aging based on the human stem cell models.

  Research work
  Establishment and evaluation of gene engineering approaches
  We established efficient gene engineering approaches to genetically correct mutated gene(s) in patient-specific iPSCs, and evaluate the mutation load attributable to genome editing technologies at single base pair level by Whole Genome Sequencing, and we also developed a novel TTALE imaging system that can enable high-contrast visualization of the 3D dynamics of specific genomic structures under diverse physiological and pathological contexts across a wide range of cell types in vitro and in vivo.
  Study the underlying mechanisms of human aging
  We established the platform for multiple human diseases studies and drug discovery (including Fanconi Anemia, Parkinson’s diseases, Progeria, Werner Syndrome, Artherosclerosis etc.) by a combination of human induced pluripotent stem cell and genome editing technologies. Based on the platform, we unveiled the role of WRN in maintaining heterochromatin stability and highlighted heterochromatin disorganization as a potential determinant of human aging, and demonstrated the NRF2 pathway is a novel target for preventing aging-associated stem cell attrition to treat premature aging.
  Develop novel intervention strategies of human aging
  We generated genetically enhanced human stem cells via targeted genome editing, which harbor more robust regenerative capacity and minimized risk of tumorigenesis over normal stem cells. It provides the first proof-of-concept of genetic enhancement of human stem cells, a strategy that may hold tremendous potential towards providing superior and safer stem cell replacement therapy. We also screened small molecular libraries for geroprotective compounds using Werner Syndrome human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Quercetin was identified due to its leading effects as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

 



SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. (Cell Res. 2016 Jan 15. doi: 10.1038/cr.2016.4.)



Strategy of genetically enhancement: activating NRF2 in a stable and controllable manner by single-nucleotide variation (A245G). (Cell Res. 2017. Jan 31. doi: 10.1038/cr.2017.18.)



NRF2 defect is a key contributor to premature aging in Hutchinson-Gilford progeria syndrome. (Cell. 2016. 165,1-14.)



A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. ( Science. 2015 Apr 30. pii: aaa1356.)

 

Plain English:
  Genetically accelerated and physiologically relevant human cellular aging models enable us to investigate the involvement of genomic and epigenomic alterations as well as their interplays during human aging. These models offer superior research platforms to identify novel genes and molecular pathways related to human aging. Based on these models, we aim to identify novel aging biomarkers, reveal the new aging pathways and targets, and screen for new aging associated genes and innovative drugs. Our ongoing projects include:
1. Genome-Scale CRISPR-Cas9 mediated knockout screening in human stem cell aging model;
2. Nonhuman primate model as a genetic model to study the function of human aging associated genes;
3. Develop superior human stem cells through genetic engineering;
4. Gene therapy strategy of human osteoarthritis and other aging-related diseases.

Selected publications:

  1. Zhang W1, Wan H1, Feng G1, Qu J1, Wang J, Jing Y, Ren R, Liu Z, Zhang L, Chen Z, Wang S, Zhao Y, Wang Z, Yuan Y, Zhou Q, Li W, Liu GH, Hu B.SIRT6 deficiency results in developmental retardation in cynomolgus monkeys. . 2018 in press. doi:10.1038/s41586-018-0437-z. (1equal contribution).
  2. Zhang W, Song M, Qu J*, Liu GH*. Epigenetic Modifications in Cardiovascular Aging and Diseases.Circ Res. 2018 in press. (*Corresponding author)
  3. Yang J, Li J, Suzuki K, Liu X, Wu J, Zhang W, Ren R, Zhang W, Chan P, Izpisua Belmonte JC, Qu J*, Tang F*, Liu GH*. Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding. Cell Res. 2017 Jul 7. doi: 10.1038/cr.2017.86.(*Corresponding author)
  4. Ren R, Deng L, Xue Y, Suzuki K, Zhang W, Yu Y, Wu J, Sun L, Gong X, Luan H, Yang F, Ju Z, Ren X, Wang S, Tang H, Geng L, Zhang W, Li J, Qiao J, Xu T*, Qu J*, Liu GH*. Visualization of aging-associated chromatin alterations with an engineered TALE system. Cell Res. 2017. Jan 31. doi: 10.1038/cr.2017.18. (*Corresponding author)
  5. Kubben N, Zhang W#, Wang L, Voss T, Yang J, Qu J#, Liu GH*, Misteli T* Repression of the antioxidant NRF2 pathway in premature aging. Cell. 2016. 165,1-14. Highlighted by Cell, doi: http://dx.doi.org/10.1016/j. cell.2016.05.061 (#Co-senior author)
  6. Suzuki K, Tsunekawa Y, Hernandez-Benitez R, Wu J, Zhu J, Kim EJ, Hatanaka F1, Yamamoto M, Araoka T, LiZ, Kurita M, Hishida T, Li M, Aizawa E, Guo S, Chen S, Goebl A, Soligalla RD, Qu J, Jiang T, Fu X, Jafari M, Esteban CR, Berggren WT, Lajara J, Nu?ez-Delicado E, Guillen P, Campistol JM, Matsuzaki F, Liu GH, Magistretti P, Zhang K, Callaway EM, Zhang K, Belmonte JC. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature. 2016. 540(7631):144-149. doi: 10.1038/nature20565.
  7. Pan H, Guan D, Liu X, Li J, Wang L, Wu J, Zhou J, Zhang W, Ren R, Zhang W, Li Y, Yang J, Hao Y, Yuan T, Yuan G, Wang H, Ju Z, Mao Z, Li J, Qu J*, Tang F*, Liu GH*. SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Res. 2016 Jan 15. doi: 10.1038/cr.2016.4. (*Corresponding author)
  8. Zhang W1, Li J1, Suzuki K1, Qu J1, Wang P, Zhou J, Liu X, Ren R, Xu X, Ocampo A, Yuan T, Yang J, Li Y, Shi L, Guan D, Pan H, Duan S, Ding Z, Li M, Yi F, Bai R, Wang Y, Chen C, Yang F, Li X, Wang Z, Aizawa E, Goebl A, Soligalla RD, Reddy P, Esteban CR, Tang F, Liu GH, Belmonte JC. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science. 2015 Apr 30. pii: aaa1356. (1equal contribution)
  9. Suzuki K1, Yu C1, Qu J1, Li M1, Yao X, Yuan T, Goebl A, Tang S, Ren R, Aizawa E, Zhang F, Xu X, Soligalla R, Chen F, Kim J, Kim NY, Liao HK, Benner C, Esteban CR, Jin Y, Liu GH*, Li Y* , Belmonte JC*.Targeted gene correction in human disease-specific induced pluripotent stem cells minimally impacts whole-genome mutational load. Cell Stem Cell. 2014. 2014; 15, 31–36. (1equal contribution)
  10. Liu GH1, Qu J1, Suzuki K1, Nivet E, Li M, Montserrat N, Yi F, Xu X, Ruiz S, Zhang W, Ren B, Wagner U, Kim A, Li Y, Goebl A, Kim J, Soligalla R, Dubova I, Thompson J, Yates JIII, Esteban C, Sancho-Martinez I, Belmonte JC. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature, 2012,491(7425):603-7. Highlighted by Nature Reviews Neurology (Nature Reviews Neurology | doi:10.1038/nrneurol.2012.230) (1equal contribution)
  11. Liu GH1, Suzuki K1, Qu J1, Sancho-Martinez I, Yi F, Li M, Kumar S, Nivet E, Kim J,  Soligalla RD, Dubova I, Goebl A, Plongthongkum N, Fung HL, Zhang K, Loring J, Laurent L, and Belmonte JC. Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell Stem Cell. 2011, 8(6):688-94. Highlighted by Nature (Nature 474, 8. doi:10.1038/474008c) and Cell Stem Cell (Cell Stem Cell 9, 2: 93-94) (1equal contribution).
  12. Qu J1, Nakamura T1, Cao G, Mckercher S, Lipton S. S-Nitrosylation Activates Cdk5 and Contributes to Synaptic Spine Loss Induced by β-Amyloid Peptide. Proceedings of the National Academy of Sciences. 2011, 108(34):14330-5. doi: 10.1073/pnas.1105172108 (1equal contribution).
  13. Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurian L, Walsh C, Thompson J, Boue S, Fung HL, Sancho-Martinez I, Zhang K, Iii JY, Belmonte JC. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature. 2011; 14;472: 221-5.doi: 10.1038/nature09879.