Supervisors
Liu, Baohua (Distinguished Professor)
Basic Medical School
Distinguished Professor
Department of Biochemistry and Molecular Biology
NAME: Liu, Baohua
BIOGRAPHICAL SKETCH
POSITION TITLE:Professor, Shenzhen University Health Science Center
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EDUCATION/TRAINING
? INSTITUTION AND LOCATION | ? DEGREE ? | Completion Date? | ? FIELD OF STUDY |
Peking University, Beijing, China | B. S. | 07/1999 | Biochemistry and Molecular Biology |
University of Hong Kong, Hong Kong | Ph.D. | 08/2007 | Mechanism of aging |
University of Hong Kong, Hong Kong | Postdoctoral | 02/2011 | Mechanism of aging |
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A.?? Personal Statement
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I earned my B.S. degree from Peking University, and my Ph.D. from the University of Hong Kong. I completed my postdoctoral training at the University of Hong Kong and was promoted to Research Assistant Professor in 2011. In 2014, I joined the Shenzhen University Health Science Center as a Distinguished Professor. During my career, I have received awards including the Li Ka Shing Prize,??and the National Excellent Young Researcher Award. My research interests are centered on the mechanisms and interventions of aging. Particularly, I am interested in (1) the roles of longevity-promoting sirtuins in genomic integrity, circadian rhythms, cancer stemness and metastasis; (2) the contributing roles of adult stem cells and somatic senescence in organism aging; (3) the systemic factors and intercellular/interorgan communications that are critical for aging; and (4) therapeutic agents that slow down aging. My research projects are supported by research grants from the Natural Science Foundation of China, National R&D Program of China, the Research Grants Council of Hong Kong, the Natural Science Foundation of Guangdong Province, and the Shenzhen Science and Technology Innovation Commission. My current team includes three junior faculties, five postdocs, four postgraduate students and three research assistants.
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? B.???? Positions and Honors
? Positions and Employment
? 04/11 – 03/16? Research Assistant Professor, Faculty of Medicine, University of Hong Kong, Hong Kong? ? 03/14 – present? ? ? Distinguished Professor, Shenzhen University Health Science Center, Shenzhen,? ? ?China
? Honors and Awards
?2014- National Excellent Young Researcher Award (Natural Science Foundation of China)
?2008- Li Ka Shing Prize for Best PhD Thesis (University of Hong Kong) 2007- Dr KP Stephen Chang Gold Medal (University of Hong Kong) 2006- Outstanding Research Output Award (University of Hong Kong) 2005- Hong Kong Young Scientist Award (Hong Kong)
A.? ? ??Contributions to Science (*Corresponding/co-corresponding authorship; #First authorship/co-first? ? authorship)
1.? ? ? ?1. Genomic Instability and Epigenetic Regulation of Aging
? ? Aging is the gradual decline of physiological functions. Increasing evidence supports that normal aging shares similar molecular mechanisms (in part) with Progeria, which is an early onset premature aging syndrome. We revealed that Progeria is associated with defective DNA repair, indicated by delayed recruitment of DNA damage checkpoint response factors and accumulation of unrepaired/irreparable DNA damage (Nature Medicine 2005#). We found hypo-acetylated histone H4 (H4K16ac) and hyper-methylated H3 (H3K9me3) in Progeria cells; feeding mice an HDAC inhibitor (sodium butyrate) or genetic ablation of the H3K9me3 methyltransferase Suv39h1 could rescue abnormal heterochromatic modifications and extend lifespan (PNAS 2011; Nat Comms 2013#). In addition, we found that defective ATM-KAP-1 signaling leads to delayed chromatin remodeling, which at least partially underlies impaired DNA repair and early senescence in Progeria (Aging Cell 2013#).
? Opposite to aging, whether and how robust DNA repair machinery promotes longevity is elusive. We demonstrated that low dose of chloroquine activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs lifespan. Mechanistically, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. The data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity (eLife 2018*).
1)??(1)?Baohua Liu, Jianming Wang, Kui Ming Chan, Wai Mui Tjia, Wen Deng, Xinyuan Guan, Jian-dong Huang, Kai Man Li, Pui Yin Chau, David J Chen, Duanqing Pei, Alberto M Pendas, Juan Cadi?anos, Carlos L?pez-Ot?n, Hung Fat Tse, Chris Hutchison, Junjie Chen, Yihai Cao, Kathryn SE Cheah, Karl Tryggvason, Zhongjun Zhou*. Genomic instability in laminopathy-based premature aging. Nature Medicine 2005; 11 (7), 780-785. Impact factor, 27.363
2)? ? (2)Baohua Liu, Zimei Wang, Le Zhang, Shrestha Ghosh, Huiling Zheng, Zhongjun Zhou*. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nature Communications 4, Article number: 1868, 21 May 2013 (doi:10.1038/ncomms2885). Impact?factor, 11.47
3)? ? (3)?Vaidehi Krishnan#, Maggie Zi Ying Chow#, Zimei Wang#, Le Zhang#, Baohua Liu, Xinguang Liu, Zhongjun Zhou*. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and?premature senescence in Zmpste24-deficient mice. Sciences of the United States of America 2011 Jul 26;108 (30):12325-30. Impact factor, 9.809
1)? ? (4)Baohua Liu#, Zimei Wang#, Shrestha Ghosh, Zhongjun Zhou*. Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model. Aging Cell 2013 Apr;12(2):316-8. doi: 10.1111/acel.12035. Impact factor, 5.939.
2)? ? (5)?Minxian Qian#, Zuojun Liu#, Linyuan Peng, Xiaolong Tang, Fanbiao Meng, Ying Ao, Mingyan Zhou, Ming Wang, Xinyue Cao, Baoming Qin, Zimei Wang, Zhongjun Zhou, Guangming Wang, Zhengliang Gao, Jun Xu, Baohua Liu*. Boosting ATM Activity alleviates ageing and extends lifespan in a mouse model of progeria. eLife 2018 May 2;7. pii: e34836. doi: 10.7554/eLife.34836.
1.? ? 2.Sirtuins in Aging and Longevity
The NAD+-dependent deacylase sirtuins (Sirt1-7) regulate various signaling pathways and cell activities. Increased Sirt1 activity has beneficial effects in animal models and human diseases; Sirt1-activating compounds elicit therapeutic effects on various metabolic and degenerative disease models. We found that nuclear protein Lamin A directly binds to and enhances Sirt1 deacetylase activity, thus providing a mechanistic explanation for the anti-ageing effect of resveratrol, a mimic of caloric restriction. Reduced Sirt1 deacetylase activity leads to early depletion of adult stem cells, which might underlie premature ageing caused by defective LMNA splicing (Cell Metabolism, 2012*). Lamin A also serves as an endogenous activator of SIRT6, another sirtuin member closely associated with aging/longevity. Lamin A, but not progerin, enhances SIRT6-dependent histone deacetylation and promotes SIRT6-mediated molecular events upon DNA damage. Impaired SIRT6 function is an underlying mechanism of Progeria (Cell Reports, 2015).
1)? ? (1)Baohua Liu*, Shrestha Ghosh, Xi Yang, Huiling Zheng, Xinguang Liu, Zimei Wang, Guoxiang Jin, Bojian Zheng, Brian K. Kennedy, Yousin Suh, Matt Kaeberlein, Karl Tryggvason, Zhongjun Zhou*. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metabolism, Volume 16, Issue 6, 738-750, 5 December 2012.
*Co-corresponding authorship. PubMed ID: 23217256. Impact factor, 17.565
2)? ? (2)Shrestha Ghosh, Baohua Liu, Xi Yang, Quan Hao, and Zhongjun Zhou*. Lamin A is an endogenous SIRT6 activator and promotes SIRT6-mediated DNA repair. Cell Reports 2015. Impact factor, 8.358
3)? ? ?(3)Shrestha Ghosh, SK Wong, Jiang Z, Baohua Liu, Yi Wang, Quan Hao, Vera Gorbunova, Xinguang Liu, Zhongjun Zhou. Haploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice. eLife. 2018 Feb 23;7. pii: e32127. doi: 10.7554/eLife.32127.
2.? ? ?3.?Aging and Cancer
Aging is the biggest risk factor of age-related diseases like cancer. Epidemiologic studies have revealed that the incidence of breast cancer dramatically increases with ageing. We used the GenAge Human Genes list (detailing the reported genes associated with aging/longevity) to screen for genes that correlate with breast cancer stemness. We identified pro-longevity SIRT1, which is centered in a KLF4-ALDH1A1-ALDH1A3 triangle of a functionally interacting network and is associated with epithelial-like breast cancer stem cells (CSCs) (ALDH1+) (Oncogene, under revision*). By contrast, another sirtuin member SIRT7 is associated with mesenchymal-like CSCs (CD44+). Indeed, SIRT7 serves as modulator of TGF-β signaling and suppressor of breast cancer metastasis (Nat Comms 2017*).
1)? ? (1)Xiaolong Tang#, Lei Shi#, Ni Xie#, Zuojun Liu, Minxian Qian, Fanbiao Meng, Qingyang Xu, Minyan Zhou, Xinyue Cao, Wei-Guo Zhu, Baohua Liu*. SIRT7 Antagonizes TGF-β Signaling and Inhibits Breast Cancer Metastasis. Nature Communications 2017 Aug 22;8(1):318. doi:?10.1038/s41467-017-00396-9
2)? ? (2)Lei Shi#, Xiaolong Tang#, Minxian Qian, Zuojun Liu, Fanbiao Meng, Li Fu, Zimei Wang, Wei-Guo Zhu, Jian-Dong Huang, Zhongjun Zhou, and Baohua Liu*. A SIRT1-centered Circuitry Regulates Breast Cancer Stemness and Metastasis. Oncogene, under revision.
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????????????????????????????????????????????????????????????????????????CSCs??????????????????????????Metastasis
??????????????????????????????????????????????????????????????????? ?????????? ?SIRTains restrain cancer cell plasticity
??????? D.?Research Support
Natural Science Foundation of China (NSFC; 81571374)????? 2016 to 2019
Baohua Liu, PI???????? RMB 1,440,000
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NSFC Excellent Young Researcher Award (81422016)? 2015 to 2017
Baohua Liu, PI???????? RMB 1,000,000
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NSFC Major Research Program (91439133)? 2015 to 2017
Baohua Liu, PI???????? RMB 900,000
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Research Grant Council of Hong Kong General Research Found (773313)???????? 2013 to 2016
Baohua Liu, PI? HK$ 796,750
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NSF of Guangdong Province Major Research Program (2014A030308011)??????? 2015 to 2018
Baohua Liu, PI? RMB 1,000,000
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NSF of Guangdong Province Major Research Program (2015A030308007)??????? 2016 to 2019
Baohua Liu, Co-Investigator?? RMB 1,000,000
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Shenzhen Peacock Program Innovative team fund (KQTD20140630100746562)????? 2015 to 2019
Baohua Liu, Co-Investigator???????? RMB 15,000,000
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Discipline Construction Funding of Shenzhen (2016)? 2016 to 2019
Baohua Liu, Co-Investigator RMB 10,000,000
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Shenzhen Basic Research Program (JCYJ20160226191451487)?? 2016 to 2019
Baohua Liu, PI???????? RMB 2,000,000
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Shenzhen Basic Research Program (CXZZ20140903103747568) 2015 to 2017
Baohua Liu, PI???????? RMB 1,500,000
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A.? ? ? E.?Publications
? #Equal contribution; *Corresponding authorship
? ? ? ?Minxian Qian#, Zuojun Liu#, Linyuan Peng, Xiaolong Tang, Fanbiao Meng, Ying Ao, Mingyan Zhou, Ming Wang, Xinyue Cao, Baoming Qin, Zimei Wang, Zhongjun Zhou, Guangming Wang, Zhengliang Gao, Jun Xu, Baohua Liu*. Boosting ATM Activity alleviates ageing and extends lifespan in a mouse model of progeria. eLife 2018 May 2;7. pii: e34836. doi: 10.7554/eLife.34836.
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? ? ? ?Xiaolong Tang#, Lei Shi#, Ni Xie#, Zuojun Liu, Minxian Qian, Fanbiao Meng, Qingyang Xu, Minyan Zhou, Xinyue Cao, Wei-Guo Zhu, Baohua Liu*. SIRT7 Antagonizes TGF-β Signaling and Inhibits Breast Cancer Metastasis. Nature Communications 2017 Aug 22;8(1):318. doi: 10.1038/s41467-017-00396-9
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? ? ??Ghosh S, Wong SK, Jiang Z, Liu B, Wang Y, Hao Q, Gorbunova V, Liu X, Zhou Z. Haploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice. eLife. 2018 Feb 23;7. pii: e32127. doi: 10.7554/eLife.32127.
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? ? Qiuxiang Pang#, Lili Gao#, Wenjing Hu#, Yang An#, Hongkuan Deng, Yichao Zhang, Xiaowen Sun, Guangzhong Zhu, Baohua Liu*, Bosheng Zhao*. De novo transcriptome analysis provides insights into immune related genes and the RIG-I-like receptor signaling pathway in the freshwater Planarian (Dugesia japonica). PloS One 2016. DOI: 10.1371/journal.pone.0151597
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? ? ? ?Shrestha Ghosh, Baohua Liu, Xi Yang, Quan Hao, and Zhongjun Zhou*. Lamin A is an endogenous SIRT6 activator and promotes SIRT6-mediated DNA repair. Cell Reports 2015. Impact factor, 8.358
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? ? ? Yasong Wu, Yuan Li, Hui Zhang, Yinghua Huang, Ping Zhao, Yujia Tang, Xiaohui Qiu, Yue Ying, Wen Li, Su Ni, Meng Zhang, Longqi Liu, Yan Xu, Qiang Zhuang, Zhiwei Luo, Christina Benda, Hong Song, Baohua Liu, Liangxue Lai, Xingguo Liu, Hung Fat Tse, Xichen Bao, Wai-Yee Chan, Miguel Esteban, Baoming Qin*, and Duanqing Pei*. Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming. Nature Cell Biology 2015 Jun;17(6):715-25. doi: 10.1038/ncb3172. Impact factor, 19.679
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? ? ? ?Bo Gao, Qiang Huang, Qiang Jie, Wei-Guang Lu, Long Wang, Xiao-Jie Li, Zhen Sun, Ya-Qian Hu, Li Chen, Baohua Liu, Jian Liu, Liu Yang*, Zhuo-Jing Luo*. GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs. Scientific Reports 2015 Sep 14;5:14080. doi: 10.1038/srep14080. Impact factor, 5.578
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? ? ? ?Jia Liu, Xianhui Yin, Baohua Liu, Huiling Zheng, Guangqian Zhou, Liyun Gong, Meng Li, Xueqin Li, Youya Wang, Jingyi Hu, Vaidehi Krishnan V, Zhongjun Zhou, Zimei Wang*. HP1α mediates defective heterochromatin repair and accelerates senescence in Zmpste24-deficient cells. Cell Cycle 2014 Feb 14;13(8)2014. Impact factor, 5.006
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9.??? Baohua Liu*, Zhongjun Zhou*. Activation of SIRT1 by resveratrol requires lamin A. Aging (Albany NY) 2013. *Co-corresponding authorship. Impact factor, 4.886
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10.? Shrestha Ghosh, Baohua Liu, Zhongjun Zhou*. Resveratrol activates SIRT1 in a lamin A-dependent manner. Cell Cycle 2013 Feb 25;12(6). Impact factor, 5.006
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11.? Baohua Liu, Zimei Wang, Le Zhang, Shrestha Ghosh, Huiling Zheng, Zhongjun Zhou*. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nature Communications 4, Article number: 1868, 21 May 2013 (doi:10.1038/ncomms2885). Impact?factor, 11.47
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12.? Baohua Liu*, Shrestha Ghosh, Xi Yang, Huiling Zheng, Xinguang Liu, Zimei Wang, Guoxiang Jin, Bojian Zheng, Brian K. Kennedy, Yousin Suh, Matt Kaeberlein, Karl Tryggvason, Zhongjun Zhou*. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metabolism, Volume 16, Issue 6, 738-750, 5 December 2012. *Co-corresponding authorship. PubMed ID: 23217256. Impact factor, 17.565
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13.? Baohua Liu#, Zimei Wang#, Shrestha Ghosh, Zhongjun Zhou*. Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model. Aging Cell 2013 Apr;12(2):316-8. doi: 10.1111/acel.12035. Impact factor, 5.939.
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14.? Vaidehi Krishnan#, Maggie Zi Ying Chow#, Zimei Wang#, Le Zhang#, Baohua Liu, Xinguang Liu, Zhongjun Zhou*. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Sciences of the United States of America 2011 Jul 26;108 (30):12325-30. #Equal contribution. Impact factor, 9.809; cited by 22 (Scopus)
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15.? Baohua Liu, Jianming Wang, Kui Ming Chan, Wai Mui Tjia, Wen Deng, Xinyuan Guan, Jian-dong Huang, Kai Man Li, Pui Yin Chau, David J Chen, Duanqing Pei, Alberto M Pendas, Juan Cadi?anos, Carlos L?pez-Ot?n, Hung Fat Tse, Chris Hutchison, Junjie Chen, Yihai Cao, Kathryn SE Cheah, Karl Tryggvason, Zhongjun Zhou*. Genomic instability in laminopathy-based premature aging. Nature Medicine 2005; 11 (7), 780-785. Impact factor, 27.363; cited by 203 (Scopus).
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1.??Baohua Liu, Shuangcheng Zhou, Xinguang Liu, Keyuan Zhou, Fengju Zhang, Zhongjun Zhou.?Accumulation of prelamin A compromises NF-κB-regulated B-lymphopoiesis in progeria mouse model.?BMC Longevity & Healthspan 2013, 2:1; doi: 10.1186/2046-2395-2-1 2.
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2.? ??Kui Ming Chan, Hoi Leong Xavier Wong, Guoxiang Jin, Baohua Liu, Renhai Cao, Yihai Cao, Kaisa Lehti, Karl Tryggvason K and Zhongjun Zhou*. MT1-MMP Inactivates ADAM9 to Regulate FGFR Signaling and Calvarial Osteogenesis. Developmental Cell 2012 Jun 12; 22(6):1176-90. Impact factor, 10.366.
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1.??? Dong XX, Wang YR, Qin S, Liang ZQ, Liu BH, Qin ZH, Wang Y*. P53 mediates autophagy activation and mitochondria dysfunction in kainic acid-induced excitotoxicity in primary striatal neurons. Neuroscience 2012 Apr 5;207:52-64. doi: 10.1016/j.neuroscience.2012.01.018. Impact factor, 3.327
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2.??? Baohua Liu, Raymond KH Yip, Zhongjun Zhou. Chromatin remodeling, DNA damage repair and aging.? Current Genomics Vol. 13, No.7 November 2012. Impact factor, 2.868
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3.??? Baohua Liu*, Dong-Yan Jin, Zhongjun Zhou*. From loss to gain: role for SUN1 in laminopathies. Cell & Bioscience 2012, 2:21. *Co-corresponding authorship. Impact factor, 3.321
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4.??? Bishnupriya Kar*, Baohua Liu, Zhongjun Zhou, and Yun W Lam. Quantitative nucleolar proteomics reveals nuclear re-organization during stress- induced senescence in mouse fibroblast. BMC Cell Biology 2011, 12:33 doi:10.1186/1471-2121-12-33. Impact factor, 2.844
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5.??Vaidehi Krishnan, Baohua Liu, Zhongjun Zhou*. 'Relax and Repair' to restrain aging. Aging (Albany NY).?2011 Oct;3(10):943-54. Impact factor, 4.886
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6.???Guoxiang Jin, Fengju Zhang, Kui Ming Chan, Hoi Leong Xavier Wong, Baohua Liu, Kathryn SE Cheah, Xinguang Liu, Cornelia Mauch, Depei Liu, Zhongjun Zhou*. MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development. EMBO Journal 2011; 30(11):2281-93. Impact factor, 10.748; cited by 3 (Scopus)
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7.??Baohua Liu, Zhongjun Zhou*. Lamin A/C, laminopathies and premature ageing. Histology and Histopathology 2008 Jun; 23(6):747-63. Impact factor, 2.236
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8.? ? ?Zhongjun Zhou*, Jianming Wang, Renhai Cao, Hiroyuki Morita, Raija Soininen, Kui Ming Chan, Baohua? Liu, Yihai Cao, Karl Tryggvason. Impaired angiogenesis, delayed wound healing and retarded tumor growth in Perlecan heparan sulfate deficient mice. Cancer Research 2004; 64(14): 4699-4702. Impact factor, 9.284; cited by 80 (Scopus)
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9.? ?Zhongjun Zhou*, Masayuki Doi, Jianming Wang, Renhai Cao, Baohua Liu, Kui Ming Chan, Jarkko Kortesmaa, Lydia Sorokin, Yihai Cao, Karl Tryggvason. Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice. Cancer Research 2004; 64(12): 4059-4063. (Recommended by Faculty 1000 by Lynn Matrisian, F1000 Factor 3.0). Impact factor, 9.284; cited by 25 (Scopus).
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10.? ?Jingzhou Chen, Baohua Liu, Yuqing Liu, Yu Han, Hui Yu, Yu Zhang, Lihe Lu, Yisong Zhen, Rutai Hui*. A novel gene IC53 stimulates ECV304 cell proliferation and is upregulated in failing heart. Biochemical and Biophysical Research Communications. 2002; 294(1):161-6. Impact factor, 2.281
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11.? ?Baohua Liu, Yuqing Liu, Jingzhou Chen, Zhun Wei, Hui Yu, Yisong Zhen, Lihe Lu, Rutai Hui*. CARP is a novel caspase recruitment domain containing pro-apoptotic protein. Biochemical and Biophysical Research Communications. 2002; 293(5):1396-404. Impact factor, 2.281??
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