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Zhu Chengming
Biography

Zhu Chengming is a professor and Ph.D. supervisor at the Seventh Affiliated Hospital of Sun Yat-sen University, a member of the Sun Yat-sen University's “Hundred Talents Program”. From 2003 to 2017, he worked at UT MD Anderson Cancer Center in Houston, TX, USA as a faculty member. Professor Zhu started as a tenure-track assistant professor then was promoted to a tenured associate professor. During that period, he led many research projects funded by NIH, ACS, Leukemia Society and other funding mechanisms in USA. Professor Zhu has successfully trained numbers of Ph.D. students and postdoctoral fellows. He also taught classes at the Graduate School of the University of Texas at Houston, served as director of the immunology graduate program for six years. His research interests are in the field of molecular biology, immunology, genetics, and oncology for many years. He has published nearly 40 articles successively in scientific journals such as Cell, J Exp Med, Immunity, Nature, Nature Immunology, Oncogene, Molecular Cell, Diabetes and Cell Cycle. Among these articles, Professor Zhu was either the first author and respondent author for 19 papers, particularly with two papers in Cell as the first author. He also served as a guest editor for the international journals such as American J Immunology and a guest reviewer for JBC, Journal of Cancer, Leukemia and lymphoma, Diabetologia, and Plos One. Now, Zhu has returned to China and was appointed as a professor at Sun Yat-sen University.

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RESEARCH DIRECTIONS

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???? 1. Genomic instability and tumorigenesis: Chromosomal translocation is a common type of genomic instability found in cancer cells. It is also responsible for the tumorigenesis of many cancers, such as some lymphoma, leukemia and sarcoma. However, we know very little about the molecular mechanism of chromosomal translocation, either do we know much about the tumorigenesis process caused by chromosomal translocation. Previous we did a lot of research work in this field, mainly based on animal models. The focus of ongoing research includes: 1) collect and analyze lymphoma/sarcoma patient samples and understand the DNA repair pathways involved in joining chromosomal ends; 2)create chromosomal translocation using CRISPR technique and study its consequences to the cells; 3) use mouse primary cells to create chromosomal translocation and transfer these cells into syngenic mouse to observe and investigate tumorigenesis process;

???? 2. Establish animal tumor models in immune sufficient mice: The traditional tumor animal model has been established based on immunodeficient mice. It is impossible to use these models to study new immune based cancer therapy research. The demand is there for better immune sufficient cancer animal models. We plan to 1) adaptive transfer of cells with chromosomal translocation to syngenic mice, to observe and investigate tumorigenesis process; 2) introducing CRISPR constructs using a viral vector to create chromosomal translocation in mice, to generate cancer animal model with normal immune system. These models are also an excellent material to study the how cancer cells escape immune surveillance.

???? 3. Colorectal Cancer research: Colorectal environment poses a challenge to the immune system: it requires immune tolerance to microbiota and some food antigens, yet to keep pathological microorganism and harmful substances out. Therefore, homeostasis of the immune function is a key to maintain the balance of colorectal environment. We have previously established a mouse model that under the condition of immune imbalance, immune activation leads to chronic inflammation; furthermore, when the p53 gene is mutated, the mouse succumb to aggressive colorectal cancer spontaneously. We will continue to pursue this field of research. To take advantage of clinical environment of the Seven Affiliated Hospital, we will study 1) immune balance in colorectal cancer sample; 2) the role of B lymphocytes and IgA in maintaining homeostasis of colorectal environment; 3) microbiota effects immune regulation in mouse and human, and its role in chronic inflammation; 4) the importance of p53 mutation in tumorigenesis in the chronic inflammation environment; 5) the role of beta-catenin and its dysregulation in chronic inflammation associated with colorectal cancer; 6) Further study the mechanism of chronic inflammation associated colorectal cancer;

???? 4. DNA damage and repair and diabetes: previously, we have reported that pancreatic beta-cell suffer DNA damage and in combination with p53 mutation, they undergo senescence early, leading to severe diabetes. We will continue to pursue how pancreatic cells response to DNA damage, and p53 mutation impact cell cycle and they're relational with diabetes occurrence.

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EDUCATION

1980/09 – 1984/08 Fudan University, Major BiochemistryB.S.

1986/09 – 1989/03 University of Houston, Dept of Biology,,Microbiology, M. S.

1993/09 – 1997/09 Baylor College of Medicine, Immunology Ph.D., Advisor: DrDavid B. Roth

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WORKING/RESEARCH EXPERIENCES

1997/10–2003/11 Harvard Medical School, Molecular Immunology program, Advisor: DrFrederick W. Alt,;

2003/10–2010/09 UT MD Anderson Cancer Center, Immunology, Assistant professor, tenure track,;

2010/09–2017/08,,UT MD Anderson Cancer Center, Immunology, Associate professor, tenured,;

2017/12–, Professor, the Seventh Affiliated Hospital, Sun Yat-sen Univerisity

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SOCIAL ACTIVITIES

2011/09-2014/08MD Anderson fund reviewer

2013/01-2015/01Expert reviewer for the Italy national research foundation,;

2014/01-2017-08American J Immunology guest editor,;

2018/03-nowChinese pathological society immunology committee member

2008/10-nowAAI member

2010/01American Microbiology association member,;

2003-nowChinese -American biological society member

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HONORS AND AWARDS

1989 ??????? Grant-in-aid research award from Sigma Xi,?

???????????????? The Scientific Research Society

1997????????? National Institute of Health Postdoctoral Fellowship

1997-2000 ???? Cancer Research Institute postdoctoral fellowship

2000-2002 ???? HHMI research fellow

2017-??????? 100 Talents program at the Sun Yat-sen University

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TEACHING EXPERIENCES

15 years of experience of teaching graduate classes and training graduate students ;

Ph.D, Master and postdoctoral advisor/supervisor, many of my trainees;

Coordinate and teach graduate immunology class,;

Coordinate and teach graduated advanced immunology classes;

Coordinate and organize Journal club classes for the past 14years;

Immunology graduate program director for the past eight years;

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PUBLICATIONS

1. Zou, Q., Jin, J., Hu, H., Li, H.S., Romano, S., Xiao, Y., Nakaya, M., Zhou, X., Cheng, X., Yang, P., Lozano, G., Zhu, C., Watowich, S.S., Ullrich, S.E. and Sun S.C. (2014). USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses. Nat. Immunol. 15 (6), 562-70. PMCID: PMC4032322.

2. Puebla-Osoro, N, J. Kim, Sang, Sandra, O., Zhang H., Tavana, O, M, Li, S., Wang, Y., Ma, Q., Schluns, KS and Zhu C. (2014). A novel Ku70 function in colorectal homeostasis separate from nonhomologous end-joining. Oncogene, 33 (21): 2748-57. PMID: 23752193.

3. Tavana, O, Puebla-Osoro, N, J. Kim, Sang, M, Jang, S, and Zhu C. (2013). Ku70 functions in addition to NHEJ in pancreatic beta-cells: a connection to beta-catenin regulation. Diabetes. 62 (7), 2429-38. PMCID: PMC3712041.

4. Hu ,H., Brittain ,G., Chang ,J., Puebla, N.,Jin, J., Cheng, X. Zal ,M., Xiao ,Y., Chang ,M., Zal ,T., Zhu ,C., Fu, Y and Sun, S. (2013). Otud7b controls noncanonical NF-κB activation via deubiquitination of TRAF3. Nature. 494 (7437): 371-4. PMCID: PMC3578967.

5. Tavana, O, Zhu, C (2011). Too many breaks (brakes): pancreatic beta-cell senescence leads to diabetes. Cell Cycle 10 (15): 2471-84. PMID: 21750406.

6. Darlington, Y., Nguyen, T.-A., Moon, S.-H., Herron, A., Zhu, C., Lu, X., and Donehower, L.A. (2011). Absence of Wip1 partially rescues Atm deficiency phenotypes in mice. Oncogene 31(9):1155-65, 3/2012. e-Pub 7/2011. PMCID: PMC3197977.

7. Puebla-Osorio N, Miyahara Y, Sreevidya C, Limo?n-Flores, AY, Kazimi N, Ullrich, S and Zhu C (2011). Induction of B-cell Lymphomas by UV radiation. MBC Cancer 11: 36. PMCID: PMC3041776.

8. Tavana, O, Benjamin, C., Peubla-Osorio, N., Sang, M., Ullrich, SE., Ananthaswamy, H and Zhu, C (2010). Absence of p53-depdent apoptosis leads to UV radiation hypersensitivity, enhanced immunosuppression and celluar senescence. Cell Cycle, 9 (16): 3328-36. PMCID: PMC3041166.

9. Dujka M, Puebla-Osorio N, Tavana O, Sang M, Zhu C (2009). ATM and p53 are essential in the cell cycle containment of DNA breaks during V(D)J recombination in vivo. Oncogene 29 (7): 957-65. PMID: 19915617.

10. Tavana O, Puebla-Osorio, N., Sang, M., and Zhu. C (2010) Absence of p53- dependent apoptosis combined with nonhomologous end-joining deficiency leads to a severe diabetic phenotype in mice. Diabetes. 59 (1): 135-42. PMCID: PMC2797914.

11. Puebla-Osorio, N., and Zhu, C. (2008). DNA damage and repair during lymphoid development: Antigen receptor diversity, genomic integrity and lymphomagenesis. Immunologic Research, (41): 103-122. PMID: 18214391.

12. Van Nguyen T, Puebla-Osorio N, Pang H, Dujka ME, Zhu C. (2007) DNA damage- induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model. J Exp Med. (204): 1453-61. PMCID: PMC2118600.

13. Yan, MS., Zhu, C., Liu, N., Scofield, VL.,Reid, A., Jiang, Y., Lynn, WS., Wong, PKY. (2006). ATM controls c-Myc and DNA synthesis during postnatal thymocyte development through regulating of redox state. Free Rad. Biol. Med. Published online May, 2006. PMID: 16863997.

14. Puebla-Osorio, N, Lacey, D. Alt, F.W., and Zhu, C. (2006). Early Embryonic Lethality Due to Targeted Inactivation of DNA Ligase III.Mol. Cell. Biol. 26(10): 3935-41. PMCID: PMC1489003.

15. Ahkter, S., Richie, C., Zhang, N., Behringer, R., Zhu, C., Legerski, R. (2005). Snm-1- deficient mice exhibit accelerated tumorigenesis and susceptibility to infection. Mol. Cell. Biol.25 (21), 10071-10078. PMCID: PMC1280277.

16. Dudley, D.D., Sekiguchi, J., Zhu, C., Sadofsky, M.J., Whitlow, S., DeVido, J., Monroe, R.J., Bassing, C.H., Alt F.W. (2003). Impaired V(D)J Recombination and Lymphocyte Development in Core RAG1-expressing Mice. J. Exp. Med.19 (9): 1439- 1450. PMCID: PMC2194253.

17. Rooney S, Sekiguchi, J, Zhu C, Cheng W-L, Manis J, Whitlow S, DeVito J, Foy D, Chaudhauri J, Lombard D and Alt F.W. (2002) "Leaky" phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice. Mol. Cell, 10: 1379- 1390. PMID: 12504013.

18. Zhu C, Mills K, Ferguson OD, Lee C, Manis PJ, Fleming J, Gao Y, Morton CC and Alt FW. (2002) Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations. Cell, 109(7): 811-821. PMID: 12110179.

19. Wong K, Chang S, Weiler SR, Ganesan S, Chaudhuri J, Zhu C, Artandi SE, Rudolph KL, Gottlieb GJ, Chin L, Alt FW, and DePinho RA (2000): Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nature Genetics, 26(1): 85-88. PMID: 10973255.

20. Frank KM, Sharpless NE, Gao Y, Sekiguchi JM, Ferguson DO, Zhu C, Manis JP, Horner J, DePinho RA, and Alt FW (2000): DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. Molecular Cell, 5(6): 993-1002. PMID: 10911993.

21. Sekiguchi JM, Gao Y, Gu Y, Frank K, Sun Y, Chaudhuri J, Zhu C, Cheng HL, Manis JP, Ferguson D, Davidson L, Greenberg ME and Alt FW (1999): Non-homologous end- joining proteins are required for V(D)J recombination, normal growth, and neurogenesis. Cold Spring HarbSymp Quant Biol., 64: 169-181. PMID: 11232282.

22. Gao Y, Sun Y, Frank KM, Dikkes P, Fujiwara Y, Seidl KJ, Sekiguchi JM, Rathbun GA, Swat W, Wang J, Bronson RT, Malynn BA, Bryans M, Zhu C, Chaudhuri J, Davidson L, Ferrini R, Stamato T, Orkin SH, Greenberg ME and Alt FW (1998): A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell, 95(7):891-902. PMID: 9875844.

23. Gao Y, Chaudhuri J, Zhu C, Davidson L, Weaver DT, and Alt FW (1998): A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for Ku in V(D)J recombination. Immunity, 9(3):367-376. PMID: 9768756.

24. Gu Y, Seidl KJ, Rathbun GA., Zhu C, Manis JP, van der Storp N, Davidson L, Cheng H-L, Sekiguchi JM, Frank K, Stanhope-Baker P, Schlissel MS, Roth DB, and Alt FW (1997): Growth retardation and leaky scid phenotype of Ku70-deficient mice. Immunity, 7(5): 653-665. PMID: 9390689.

25. Bogue MA, Wang C, Zhu C, and Roth DB (1997): V(D)J recombination in Ku86- deficient mice: distinct effects on coding, signal, and hybrid joints formation. Immunity, 7(1): 37-47. PMID: 9252118.

26. Zhu C, Bogue MA, and Roth DB. (1996): Thymocyte differentiation in ?-irradiated severe-combined immunodeficient mice: characterization of intermediates and products of V(D)J recombination at the T cell receptor ??locus. Eur J Immunol., 26: 2859-2865. PMID: 8977278.

27. Zhu C, Bogue MA, Lim D-S, Hasty P, and Roth DB (1996): Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination. Cell, 86: 379-389. PMID: 8756720.

28. Zhu C and Roth DB (1996): Mechanism of V(D)J recombination. In: Cancer Survey, Vol. 28: Genetic instability in cancer. Ed. J.Tooze. Imperial Cancer Research Fund, 295-309. PMID: 8977042.

29. Steen SB, Zhu C, and Roth DB (1996): Double-strand breaks, DNA hairpins, and the mechanism of V(D)J recombination. Curr Top Microbiol Immunol., 217: 61-78. PMID: 8787618. PMID: 8598286.

30. Bogue MA, Zhu C, Aguilar-Cordova E, Donehower LA and Roth DB (1996): p53 is required for both radiation induced differentiation and rescue of V(D)J recombination in scid mouse thymocytes. Genes & Development, 10: 553-565. PMID: 8598286.

31. Kabotyanski EB, Zhu C, Kallick DA, and Roth DB (1995): Hairpin opening by single- strand-specific nucleases. Nucleic Acids Research, 23: 3872-3881. PMID: 7479030.

32. Zhu C and Roth DB (1995): Characterization of coding ends in thymocytes of scid mice: implications for the mechanism of V(D)J recombination. Immunity, 2 (1): 101-112. PMID: 7600297.

33. Roth DB, Zhu C, and Gellert M (1993): Characterization of broken DNA molecules associated with V(D)J recombination. Pro Nat Acad Sci USA, 90: 10788-10792. PMCID: PMC47863.

34. Sligh JE, Jr., Hurwitz M, Zhu C, Anderson DC, and Beaudet AL (1992): An initiation codon mutation in CD18 in association with the moderate phenotype of leukocyte adhesion deficiency. J BiolChem, 267: p714-718. PMID: 1346132.

35. Zhu C, and Henney HR, Jr. (1990): Intracellular polyamine patterns during encystment of Physarumflavicomum. Can J Microbiol, 36: 266-368. PMID: 2390746.

36. Zhu C, and Henney HR., Jr (1990): DNA methylation pattern during the encystment of Physarumflavicomum. Biochem Cell Biol, 68: 944-948. PMID: 2168719.

37. Zhu C, Cumaraswamy A. and Henney HR, Jr. (1989): Comparison of polyamine and S-adenosylmethionine contents of growing and encysted Acanthamoeba isolates. Molecular & Cellular Biochemistry, 90: 145-153. PMID: 2586495.

38. Zhu C, et al. (1985): Determination of 5-methylcytosine content in normal and leukemia rats. Chinese Nature Journal, 8:39-43.?

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Email Address[email protected], or [email protected]