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Guang Peng, M.D.,Ph.D.

Present Title & Affiliation

N/A

Bio Statement

The overall goal of my laboratory is to apply the basic knowledge of genome maintenance mechanisms to early detection and cancer prevention. More specifically, by understanding and targeting the DNA repair network, our research aim to address two key questions: (1) Can we identify genetic alterations in the DNA repair network at early stages of carcinogenesis, particularly during the transition from premalignant lesions to cancer? (2) Can we identify targeted prevention strategies for the premalignant lesions with particular genetic alterations? Recent work in my laboratory explores the following directions.

 1.      Identify genetic alterations in the DNA repair network that occur at early stage of carcinogenesis   
We aim to investigate the novel functions of chromatin remodeling complex SWI/SNF, human nucleases/helicases DNA2 and mutational enzyme APOBEC3B in promoting tumorigenesis by both in vitro and in vivo studies, which may lead to identification of new strategy for early detection and intervention. We are also work to understand how environmental and endogenous factors reshape the landscape of cellular genome by targeting epigenetic regulatory machineries.

 2.      Discover novel agents targeting the DNA repair network by genetic and chemical approaches 
We aim to utilize chemical screening and bioinformatics’ tools as our drug-discovery platforms to systematically identify chemical compounds that target the DNA repair network. We will determine whether the reduction of cellular tolerance to replication stress by modulating DNA repair process would lead a synthetic lethality interaction in premalignant cells with hyperactive DNA replication. These candidate compounds will be tested for their cancer preventive and therapeutic effects.

3.      Develop systems biology approaches to understand the dynamics of the DNA repair network in tumor evolution 
We aim to utilize network-based mathematical modeling and molecular biology approaches to understand and target the DNA repair network. These new interdisciplinary approaches will offer a revolutionary conceptual framework to determine the compound effect of the DNA repair network rather than focusing on an individual repair gene’s function in tumorigenesis.

Office Address

The University of Texas MD Anderson Cancer Center
Basic Science Research Building
1515 Holcombe Blvd.
Unit Number: 1013
Houston, TX 77030
Room Number: S7.8336B
Phone: 713-834-6151
Fax: 713-834-6350
Email: gpeng@mdanderson.org

Education & Training

Degree-Granting Education

2005 University of South Carolina School of Medicine, Columbia, SC, PHD, Biomedical Sciences
2002 Tongji Medical University, Wuhan, China, MD, Medicine

Honors and Awards

2014-2017 Susan G. Komen Career Catalyst Research Award, Susan G. Komen for the cure Foundation
2013-2015 Ovarian Cancer SPORE Career Development Award, National Cancer Institute, MD Anderson Cancer Center
2012-2014 Landon Foundation-AACR Innovator Award for Cancer Prevention Research, American Association for Cancer Research
2012 Texas Business Women Award, Texas Business Women Inc.
2011-2016 Howard Temin Pathway to Independence Award, National Cancer Institute
2010 Trainee of the Quarter, University of Texas MD Anderson Cancer Center
2009 Trainee Excellence Award, University of Texas MD Anderson Cancer Center
2008-2010 Postdoctoral Fellowship, Susan G. Komen for the Cure Foundation
2008 Oral Presentation Award, Society of Chinese Bioscientists in America Annual Synmposia, Houston, TX
2006 Edward David Lustbader Prize, Fox Chase Cancer Center, Philadelphia, PA
2006 First Place in Oral Presentation, Fox Chase Cancer Center Postdoctoral and Graduate Student Research Conference, Philadelphia, PA
2005 First Place in Oral Presentation, Graduate Student Day, The Graduate School, University of South Carolina
2005 W. Morgan Newton Research Award, School of Medicine, University of South Carolina
2004 Best Student Poster Presentation, Annual South Carolina Alliance for Cancer Chemoprevention Symposium

Selected Publications

Peer-Reviewed Original Research Articles

1. Shen J, Peng Y, Wei L, Zhang W, Yang L, Lan L, Kapoor P, Ju Z, Mo Q, Shih IeM, Uray IP, Wu X, Brown PH, Shen X, Mills GB, Peng G. ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors. Cancer Discov 5(7):752-67, 7/2015. e-Pub 6/11/2015. PMCID: PMC4497871.
2. Kapoor P, Bao Y, Xiao J, Espejo A, Yang L, Bedford MT, Peng G, Shen X. Phosphorylation-Dependent Enhancement of Rad53 Kinase Activity through the INO80 Chromatin Remodeling Complex. Mol Cell 58(5):863-9, 6/4/2015. e-Pub 5/7/2015. PMCID: PMC4485934.
3. Kapoor P, Bao Y, Xiao J, Luo J, Shen J, Persinger J, Peng G, Ranish J, Bartholomew B, Shen X. Regulation of Mec1 kinase activity by the SWI/SNF chromatin remodeling complex. Genes Dev 29(6):591-602, 3/15/2015. PMCID: PMC4378192.
4. Lee HJ, Lan L, Peng G, Chang WC, Hsu MC, Wang YN, Cheng CC, Wei L, Nakajima S, Chang SS, Liao HW, Chen CH, Lavin M, Ang KK, Lin SY, Hung MC. Tyrosine 370 phosphorylation of ATM positively regulates DNA damage response. Cell Res 25(2):225-36, 2/2015. e-Pub 1/20/2015. PMID: 25601159.
5. Zhang C, Peng G. Non-coding RNAs: an emerging player in DNA damage response. Mutat Res Rev Mutat Res 763:202-211, Jan-Mar, 1/2015. e-Pub 11/2014. PMID: 25795121.
6. Zhang B, Wang E, Dai H, Shen J, Hsieh HJ, Lu X,Peng G. Phosphorylation of BRCT-Repeat Inhibitor of hTERT (BRIT1) Coordinates TopBP1 Recruitment and Amplifies ATR Signaling. J Biol Chem 289((49)):34284-95, 2014, 12/2014. PMCID: PMCPMC:4256359.
7. Peng G, Chun-Jen Lin C, Mo W, Dai H, Park YY, Kim SM, Peng Y, Mo Q, Siwko S, Hu R, Lee JS, Hennessy B, Hanash S, Mills GB, Lin SY. Genome-wide transcriptome profiling of homologous recombination DNA repair. Nat Commun 5:3361, 2014. PMCID: PMC4017859.
8. Zhang Y, Wang H, & Peng G. Identify key links in the DNA repair network regulated by tumor suppressors PTEN and BRCA1 through maximum flow analysis. Far East Journal of Mathematical Sciences (FJMS) Special Volume 2013(Part VI):577-586, 12/2013.
9. Meng L, Lin T, Peng G, Hsu JK, Lee S, Lin SY, & Tsai RY. Nucleostemin deletion reveals an essential mechanism that maintains the genomic stability of stem and progenitor cells. Proc Natl Acad Sci U S A 110(28):11415-20, 2013, 7/2013. PMCID: PMCPMC3710807.
10. Hu R, Wang E, Peng G, Dai H, Lin SY. Zinc Finger Protein 668 interacts with Tip60 to promote H2AX acetylation after DNA damage. Cell Cycle 12(13):2033-41, 7/2013. e-Pub 6/2013. PMCID: PMC3737306.
11. Zhang, B, Wang, E, Dai, H, Hu, R, Liang, Y, Li, K, Wang, G, Peng G, & Lin, SY. BRIT1 regulates p53 stability and functions as a tumor suppressor in breast cancer. Carcinogenesis, 6/2013. e-Pub 6/2013. PMID: 23729656.
12. Wan G, Zhang X, Langley RR, Liu Y, Hu X, Han C, Peng G, Ellis LM, Jones SN, Lu X. DNA damage-induced nuclear export of precursor microRNAs is regulated by the ATM-AKT pathway. Cell Rep 3(6):2100-12, 6/2013. e-Pub 6/2013. PMCID: PMC3796289.
13. Wan G, Mathur R, Hu X, Liu Y, Zhang X, Peng G, and Lu X. Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal 25(5):1086-95, 5/2013. e-Pub 2/2013. PMCID: PMCPMC3675781.
14. Wang H, Peng G. Mathematical Model of Dynamic Protein Interactions Regulating p53 Protein Stability for Tumor Suppression. Comput Math Methods Med 2013:358980, 2013. e-Pub 12/2013. PMCID: PMC3888710.
15. Park YY, Jung SY, Jennings NB, Rodriguez-Aguayo C, Peng G, Lee SR, Kim SB, Kim K, Leem SH, Lin SY, Lopez-Berestein G, Sood AK, Lee JS. FOXM1 mediates Dox resistance in breast cancer by enhancing DNA repair. Carcinogenesis 33(10):1843-53, 10/2012. e-Pub 5/2012. PMCID: PMC3529559.
16. Peng G, Dai H, Zhang W, Hsieh HJ, Pan MR, Park YY, Tsai RY, Bedrosian I, Lee JS, Ira G, Lin SY. Human nuclease/helicase DNA2 alleviates replication stress by promoting DNA end resection. Cancer Res 72(11):2802-13, 6/2012. e-Pub 4/2012. PMCID: PMC3367086.
17. Pan MR, Hsieh HJ, Dai H, Hung WC, Li K, Peng G, Lin SY. Chromodomain helicase DNA-binding protein 4 (CHD4) regulates homologous recombination DNA repair and its deficiency sensitizes cells to poly (ADP-ribose) polymerase (PARP) inhibitor treatment. J Biol Chem 287(9):6764-72, 2/2012. e-Pub 1/2012. PMCID: PMC3307306.
18. Zhang W, Peng G, Lin SY, Zhang P. DNA damage response is suppressed by high CDK1 activity in mitotic mammalian cells. J Biol Chem 286(41). e-Pub 8/2011. PMCID: PMCPMC3195557.
19. Pan MR, Peng G, Hung WC, Lin SY. Monoubiquitination of H2AX Protein Regulates DNA Damage Response Signaling. J Biol Chem 286(32):28599-607, 8/2011. e-Pub 6/2011. PMCID: PMC3151101.
20. Hu R, Peng G, Dai H, Breuer EK, Stemke-Hale K, Li K, González-Angulo AM, Mills GB, Lin SY. ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer. Cancer Res 71:6524-6534, 2011. e-Pub 8/2011. PMCID: PMCPMC3193577.
21. Tian L, Peng G, Parant JM, Leventaki V, Drakos E, Zhang Q, Parker-Thornburg J, Shackleford TJ, Dai H, Lin SY, Lozano G, Rassidakis GZ, Claret FX. Essential roles of Jab1 in cell survival, spontaneous DNA damage and DNA repair. Oncogene. e-Pub 8/2010. PMID: 20802511.
22. Bellodi C, Krasnykh O, Haynes N, Theodoropoulou M, Peng G, Montanaro L, Ruggero D. Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. Cancer Res 70(14):6026-35, 7/2010. e-Pub 6/2010. PMCID: PMC2913864.
23. Peng G, Yim EK, Dai H, Jackson AP, Burgt I, Pan MR, Hu R, Li K, Lin SY. BRIT1/MCPH1 links chromatin remodelling to DNA damage response. Nat Cell Biol 11(7):865-72, 7/2009. e-Pub 6/2009. PMCID: PMC2714531.
24. Yim EK,Peng G, Dai H, Hu R, Li K, Lu Y, Mills GB, Meric-Bernstam F, Hennessy BT, Craven RJ, Lin SY. Rak functions as a tumor suppressor by regulating PTEN protein stability and function. Cancer Cell 15(4):304-14, 4/2009. PMCID: PMC2673492.
25. Peng G, Wargovich MJ, Dixon DA. Anti-proliferative effects of green tea polyphenol EGCG on Ha-Ras-induced transformation of intestinal epithelial cells. Cancer Lett 238(2):260-70, 7/2006. e-Pub 9/2005. PMID: 16157446.
26. Peng G, Dixon DA, Muga SJ, Smith TJ, Wargovich MJ. Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis. Mol Carcinog 45(5):309-19, 5/2006. PMID: 16508969.
27. Yoon A, Peng G, Brandenburger Y, Brandenburg Y, Zollo O, Xu W, Rego E, Ruggero D. Impairments in IRES-mediated translational control underlie X-linked dyskeratosis congenita. Science 312(5775):902-906, 5/2006. PMID: 16690864.

Invited Articles

1. Tu W, Wang H & Peng G. Synthetic lethality as a promising approach for targeted cancer prevention. Cancer and Clinical Research 2(a15), 9/2014.
2. Peng G, Woodman & Mills G. RADical response puts an exceptional responder in HKmate: a synthtic lethal curative repsonse to DNA-Damaging chemotherapy. Cancer Discovery 4:988-990, 2014. PMCID: PMCPMC4155513.

Grant & Contract Support

Title: Targeting the APOEBC3B-induced mutator phenotype for preventing breast cancer
Funding Source: Susan G. Komen for the Cure Foundation
Role: Principal Investigator
Duration: 9/1/2014 - 8/31/2017
 
Title: Role of DNA2 nuclease in cellular tolerance of replication stress and telomere maintenance-Implications for cancer biology and anticancer therapy
Funding Source: Cancer Prevention & Research Institute of Texas (CPRIT)
Role: Co-Principal Investigator
Duration: 8/31/2014 - 8/30/2017
 
Title: Targeting the threshold of replication stress as a novel approach for pancreatic cancer prevention
Funding Source: Duncan Family Institute
Role: Principal Investigator
Duration: 8/1/2014 - 7/30/2016
 
Title: Targeting ARID1A-deficiency in ovarian cancer
Funding Source: MDACC Ovarian Cancer SPORE Career Development Award
Role: Principal Investigator
Duration: 9/1/2013 - 8/31/2015
 
Title: Targeting the DNA Repair Network as a Novel Approach for Cancer Research
Funding Source: American Association for Cancer Research (AACR)
Role: Principal Investigator
Duration: 7/1/2012 - 6/30/2014
 
Title: Understanding & Targeting the DNA Repair Network in Cancer
Funding Source: NIH/NCI
Role: Principal Investigator
Duration: 7/1/2011 - 6/30/2016

Last updated: 3/23/2015