NAME: Wang, Zimei

POSITION TITLE: Professor, Biochemistry and Molecular of Biology; Associate Dean of the School of Basic Medical Science, Health Science Center, Shenzhen University.

EDUCATION/TRAINING

INSTITUTION AND LOCATION	DEGREE	Completion Date MM/YYYY	FIELD OF STUDY
Hebei medical college, Hebei, China Peking Union Medical College, Beijing, China Peking Union Medical College, Beijing, China	B.Med M.Med. M.D.	07/1992 07/1995 07/1998	Medicine Endocrinology,Medicine Endocrinology,Medicine

 

A.      Personal Statement

My research interests are in the area of aging and anti-aging molecular mechanisms. I mainly focus on the pathogenesis of premature aging syndrome, epigenetic changes underlying the aging process related to nuclear matrix microenvironment and chromatin dynamics, and screening anti-aging small molecule compounds. These projects are supported by grants from the National Natural Science Foundation of China (NSFC) and the Basic Research Foundation of Shenzhen. I have published >20 original papers in SCI journals such as PNAS, Aging Cell, and Cell Cycle. These reports have been cited in total >300 times. I received the Shenzhen Overseas High-level Talent award in 2014 and I am now the Principal Investigator of the Shenzhen Key Laboratory for Anti-aging and Regenerative Medicine. I am a member of the Aging and Anti-aging Scientific Committee of Gerontological Society of China, and a member of the Biochemistry and Molecular Biology Society of Shenzhen. I am currently mentoring one postdoctoral fellow and three MSc candidates.

 

B.      Positions and Honors

Positions and Employment

03/1999 – 05/2005      Lecturer, Associate Professor, Department of Biochemistry and Molecular Biology, Basic Medical School, Health Science Center, Peking University, Beijing, China

 

05/2005 – 07/2006     Deputy Dean of Teaching Affairs, Department of Biochemistry and Molecular Biology, Basic Medical School, Health Science Center, Peking University, Beijing, China

 

09/2006 – 08/2009      Research Associate, Department of Biochemistry, Li Ka Shing Faculty of Medicine, Hong Kong University, Hong Kong, China

 

09/2009 – 05/2015      Associate Professor, Professor, Department of Biochemistry and Molecular of Biology, School of Medicine, Shenzhen University, Shenzhen, China

 

06 /201 5 – present       Associate Dean, School of Basic Medical Science, Health Science Center, Shenzhen University, Shenzhen, China

Organizing Meetings

1.    Co-organizer, the 5^th Aging and Anti-aging Academic Conference of China, Apr 11-12th, 2015, Shenzhen

2.    Co-organizer, the 1^st Annual Conference of Southern China society of Biochemistry and Molecular Biology, Dec 17-19^th, 2015, Shenzhen

3.    Co-organizer, the 1^st Medical Youth Forum of the Chinese Society of Biochemistry and Molecular Biology, Apr 20-23th, 2016, Shenzhen.

4.    Co-organizer, the 2^nd Medical Youth Forum of the Chinese Society of Biochemistry and Molecular Biology, Apr 15-18th, 2017, Shenzhen.

5.    Co-organizer, the 3^rd Medical Youth Forum of the Chinese Society of Biochemistry and Molecular Biology, Apr 20-22th, 2018, Shenzhen

 

Other Experience and Honors

1.    NSFC peer reviewer (Gerontology and Geriatrics): 2010-2017

2.    Peer reviewer of Aging-US, Scientific Report, Chinese Journal of Biochemistry and Molecular Biology: 2012-2017

3.    Shenzhen Overseas High-level Talent Award: 2014

 

C.      Contributions to Science (*: corresponding/co-corresponding author)

Specific point mutations in lamin A gene or a deficiency in the lamin A-processing enzyme, Zmpste24, cause premature aging phenotype in humans and mice, accompanied by genomic instability and early cellular senescence due to the delayed recruitment of repair proteins to sites of DNA damage. We searched histone modifications for the underlying responsible chromatin remodeling and found histone H4K16 was hypoacetylated. This defect was attributed to the reduced association of a histone acetyltransferase Mof to the nuclear matrix. Mof overexpression or histone deacetylase inhibition promoted repair protein recruitment to DNA damage sites and substantially ameliorated aging-associated phenotypes. The life-span of Zmpste24^-/- mice was also extended upon exposure to a histone deacetylase inhibitor, sodium butyrate, that was added to the drinking water. These results shed light on how chromatin modifications regulate the DNA damage response and suggest that the reversal of epigenetic marks could be an attractive therapeutic strategy against laminopathy-based progeroid pathologies. (PNAS 2011).

 

ATM-mediated phosphorylation of KAP-1 triggers chromatin remodeling and facilitates the loading and retention of repair proteins at DNA lesions. We showed that ATM-Kap-1 signaling is compromised in Zmpste24^-/- MEFs, leading to defective DNA damage-induced chromatin remodeling. Knocking down Kap-1 rescues impaired chromatin remodeling, defective DNA repair and early senescence in Zmpste24^-/- MEFs. Thus, ATM-Kap-1-mediated chromatin remodeling has a critical role in premature aging, carrying notable implications for progeria therapy (Aging cell 2013).

 

H3K9 trimethylation is up-regulated in Zmpste24-deficent MEFs. As such, we focused on the heterochromatin protein 1(HP1), which maintains heterochromatin structure together with H3K9 trimethylation by hydrogen bond at Thr50. The level of HP1α was significantly increased and remarkably associated with the nuclease-resistant nuclear matrix fraction in Zmpste24^-/- cells,. After DNA damage, the peak of HP1α Thr50 phosphorylation was significantly compromised, which correlated with delayed maximal formation of γ-H2AX foci in Zmpste24^-/- MEFs. Furthermore, knocking down HP1α alleviated the delayed DNA damage response and accelerated senescence, as evidenced by the rescue of the delayed γ-H2AX foci formation, downregulation of p16, and reduction of senescence-associated β-galactosidase activity. These findings establish a functional link between prelamin A, HP1α, chromatin remodeling, DNA repair, and early senescence in Zmpste24-deficient mice, and suggest a potential therapeutic strategy for laminopathy-based premature aging based on HP1α (Cell Cycle 2014).

 

We are now studying the kinases that regulate HP1 phosphorylation in the DNA damage response and their functions associated with laminopathy-based premature aging and physiological aging. We are screening small molecular compounds that may prevent of attenuate the aging progress.

 

D.      Research Support

E.     

Ongoing Research Support

NSFC (China) (81471407)                                       01/2015 to 12/2018

Zimei Wang, Chief investigator                                   ￥700,000

The role of CK2 in laminopathy-based premature aging

 

NSFC (China) (91439133)                                       01/2015 to 12/2018

Zimei Wang, Investigator                                          ￥1000,000

Endothelial Aging and Stem Cell-based Therapy in Progeria

 

Shenzhen Science and Technology Innovation Commission grant (JCYJ20160520170240403)        

Zimei Wang, Chief investigator                                                         03/2017 to 03/2019, ￥300,000

TBB attenuates DNA damage induced early aging.

 

Completed Research Support

Shenzhen Science and Technology Innovation Commission grant (JCYJ20140418095735635)                                                                                                             01/2015 to 12/2017

Zimei Wang, Chief investigator                             ￥300,000

The study of functional alteration of casein kinase 2 triggers cellular senescence

 

NSFC (China) (81070270)                                        01/2011 to 12/2013

Zimei Wang, Chief investigator                                   ￥350,000

The role of HP1 involved in genomic instability contributes to accelerated aging.

 

Shenzhen Science and Technology Innovation Commission grant (JC201005280552A)                                                                                                                       01/2011 to 12/2014

Zimei Wang, Chief investigator                             ￥100,000

The study of functional alteration of casein kinase 2 triggers cellular senescence

 

Shenzhen University                                               06/2010 to 05/2012

Zimei Wang, Chief investigator                             ￥50,000

Heterochromatin DNA Damage response Defects Trigger the Premature Aging

 

Shenzhen Science and Technology Innovation Commission grant (ZDSYS2014050910074667)                                                                                                            12/2014 to 12/2016

Zimei Wang, Investigator                                           ￥3000,000

The project of Shenzhen key laboratory of anti-aging and regenerative medicine

 

F.       R epresentative publications (*: corresponding author ; ^# :c o-first author)

1.      Zhang W, Li J, Suzuki K, Qu J, 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; 348(6239): 1160-1163.

2.      Liu J, Yin X, Liu B, Zheng H, Zhou G, Gong L, Li M, Li X, Wang Y, Hu J, Krishnan V, Zhou Z, Wang Z* HP1α mediates defective heterochromatin repair and accelerates senescence in Zmpste24-deficient cells. Cell Cycle 2014, 13(8), 1237-1247

3.      Liu B^#, Wang Z^#, Ghosh S, Zhou Z. Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model. Aging Cell. 2013, 12(2):316-8.

4.      Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nat Commun. 2013; 4:1868. (IF: 10.4)

5.      Krishnan V^#, Chow MZ^#, Wang Z^#, Zhang L^#, Liu B, Liu X, Zhou Z. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Acad Sci USA. 2011, 108(30):12325-30.

 

G.      Book chapters

1.      Wang Z . Chapter 26 ： Omics and Medicine. Biochemistry and molecular biology made easy, Editor-in-chief: Yi xia. Peking University Health Science Center publisher. 2015.09

2.      Wang Z. Chapter 7: amino acids metabolism. Biochemistry in Medicine, Editor-in-chief: Ni Juhua, Jia Yieping, Liu Guanchang, Peking University Health Science Center publisher. 2014.10

3.      Wang Z . Chapter 6: Mechanisms of Lipids; Chapter18: The Chemistry of Liver. Biochemistry. Biochemistry (4), Editor-in-chief: Li Gang, Co-Editor-in-chief: Wang Z. Peking University Health Science Center publisher. Beijing, 2006, 6

4.      Wang Z. Chapter 27: Genomics and Medicine. Biochemistry and Molecular Biology: Learning Guide for Graduate Students. Editor-in-chief: Zhang Youzhang, Cha Xiliang, Li Gang. Scientific and Technological Literature Publishing House. Beijing, 2005.10

5.      Wang Z and Jia H. Chapter16: Genomics and Medicine. Biochemistry (Third Edit). Peking University Health Science Center publisher. Beijing, 2005.2