UNMC College of Dentistry
4000 East Campus Loop South
Lincoln NE 68583-0740
Telephone: (402) 472-5903
Fax: (402) 472-2551
- B.S. (Biology), University of Science and Technology of China, Hefei, China
- Ph.D. (Molecular Medicine), Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX
- Course Instructor, Biochemistry for Dental Students (ORBI 545)
- Course Instructor, Advanced Oral Biology (OBIO 855)
- Our research areas include cell cycle regulation and the DNA damage response (DDR). We are particularly interested in the connection between these pathways and human cancer. Dysregulation of these pathways has been shown to be a causal factor in cancer progression, and therapeutic solutions to improve cancer treatment through manipulating the DDR or cell cycle machinery are dearly sought. It is, however, imperative to delineate the mechanistic basis of these pathways in order to fully translate these studies into clinical benefits. These fundamental and evolutionarily-conserved processes are extremely complicated in nature, and scientific efforts to understand them are likely to benefit from utilization of comprehensive experimental systems. We combine reconstitutive studies in Xenopus egg extracts and other in vitro systems with functional investigations in mammalian cells and tumor models to reveal new insights into these processes. With this comprehensive panel of experimental systems, we are poised to make unique and substantial contributions in this research field.
- A specific interest of our research is the cellular recovery process from DNA damage. Upon completion of DNA repair, the recovery process de-activates the DDR, allowing the cell to return to normal cell cycle progression. This is an important process that determines cell fate post DNA damage or chemotherapy. However, the recovery mechanism is less understood compared to activation of the DDR. We have developed Xenopus egg extracts as an experimental system to recapitulate this process. We recently reported novel involvement of Greatwall (Gwl) kinase in this pathway—Gwl functions to regulate the DNA damage response, and promote cell recovery from DNA damage. Interestingly, we showed that Gwl is frequently upregulated in cancer, in correlation with cancer progression, tumor recurrence, and poor patient survival; suppression of Gwl expression sensitized resistant cancer cells to cisplatin, while sparing normal cells. Building on these findings, we will 1) delineate detailed mechanisms by which Gwl regulates cell cycle progression and DNA damage recovery, and 2) evaluate new therapeutic agents that specifically target Gwl as potential anti-cancer drugs.
- Another focus of our research is protein phosphatase-dependent cell cycle and DDR regulation and its implication for cancer progression and therapy. The current explanation for cell cycle regulation centers on Cdk and other cell cycle kinases. Likewise, serine/threonine kinases are known to play central roles in the DDR. By comparison, serine/threonine phosphatases, particularly PP1 and PP2A, that antagonize kinase action were less studied; the role and identity of specific protein phosphatase complexes in both the cell cycle and DDR remain largely unknown. Recent studies from our laboratory and others revealed a number of Ser/Thr phosphatase complexes involved in cell cycle and DDR regulation. Emerging evidence also suggests that these phosphatases are related to human cancers. Our long-term goal is to systematically study the function, regulation, and cancer connection of cell cycle and DDR phosphatases. We identified PP1 nuclear targeting subunit (Pnuts) as an essential regulator of mitotic progression, and revealed that Pnuts expression is modulated during the cell cycle via APC/C-mediated proteolysis. More recently, we discovered that Pnuts and PP1 fine-tune the dynamic phosphorylation of DNA-PKcs after DNA damage to mediate NHEJ. The function, cancer connection, and potential therapeutic targeting of Pnuts will be further investigated.
- UNMC Pamela and Fred Buffett Cancer Center, “Protein phosphatases-dependent regulation of the cell cycle and DNA damage responses,” Principal Investigator, $50,000,, 7/1/2015 - 6/30/2016
- National Institute of Health, UNMC Nebraska Center for Cellular Signaling, “Biochemical investigation of oxidative DNA damage responses,” Pilot project Principal Investigator, $100,000, 4/1/2014 - 6/30/2015
- National Institute of Health, “DNA damage checkpoint recovery and cancer,” Principal Investigator, $1,540,000, 4/1/2013 - 3/31/2018
- NIH/CoBRE, UNMC Nebraska Center for Cellular Signaling, “The functions and regulatory mechanisms of a specific protein phosphatase 1 complex in the DNA damage response and cancer progression,” Principal Investigator: Keith Johnson; Project Leader: Aimin Peng; $375,000, 2010 - 2013
- Ren D, Fisher LA, Wang L, Williams BC, Goldberg ML, and Peng A. (2017) Cell Cycle-dependent regulation of greatwall kinase by protein phosphatase 1 and regulatory subunit 3B. J Biol Chem 292:10026-10034. PMID: 28446604.
- Zhu S, Fisher LA, Bessho T, and Peng, A. (2017) Protein phosphatase 1 and phosphatase 1 nuclear targeting subunit-dependent regulation of DNA-dependent protein kinase and non-homologous end joining. Nucleic Acid Res doi: 10.1093/nar/gkx686.
- Zhu S, Peng A. (2016) Non-homologous end joining repair in Xenopus egg extract. Sci Rep 21. PMID: 27324260.
- Luong LV, Wang L, Roberts BJ, Wahl III JK, Peng A. (2016) Cell fate determination in Cisplatin resistance and chemosensitization. Oncotarget 8110. PMID: 26993599.
- Wang, L., Guo, Q., Fisher, L.A., Liu, D., Peng, A. Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α. Cell Cycle 10:4161, 2015.
- Glanzer, J.G., Liu, S., Wang, L., Mosel, A., Peng, A., and Oakley, G.G. RPA inhibition increases replication stress and suppresses tumor growth. Cancer Res 2014 Sep 28; 74(18):5165-72. Epub 2014 Jul 28.
- Yamamoto, T.M., Wang, L., Fisher, L.A., Eckerdt, F.D., and Peng, A. Regulation of greatwall kinase by protein stabilization and nuclear localization. Cell Cycle 13(22):3565-75, 2014.
- Wang, L., Luong, V.Q., Giannini, P.J., and Peng, A. Mastl kinase, a promising therapeutic target, promotes cancer recurrence, Oncotarget 5(22):11479-11489, 2014.
- Fisher, L.A., Wang, L., Wu, L., and Peng, A. Phosphatase 1 nuclear targeting subunit Is an essential regulator of M-phase entry, maintenance and exit. J Biol Chem 2014 Aug 7; 289(34):23745-52. Epub 2014 Jul 7.13.
- Peng A. (2013) Working Hard for Recovery: Mitotic kinases in the DNA damage checkpoint. Cell Biosci 3:20.
- Wang L. Mosel AJ, Oakley GG, Peng A. (2012) Deficient DNA damage signaling leads to chemoresistance to Cisplatin in oral cancer. Mol Cancer Ther 11:2401-240
- Wang, L., Fisher, L.A., Wahl III, J.K., Peng, A. Generation and characterization of monoclonal antibodies against xenopus greatwall kinase. Hybridoma 30:469-474, 2011.
- Peng, A., Wang, L., and Fisher, L.A. Greatwall and polo-like kinase 1 coordinate to promote checkpoint recovery. Journal of Biological Chemistry 286:28996-29004, 2011.
- Peng A, Lweellyn AL, Schiemann WP, Maller JL. (2010) Repo-man controls a protein phosphatase 1-denpendent threshold for DNA damage checkpoint activation. Curr Biol 20:387-396.
- Peng A, Maller JL. (2010) Serine/Threonine phosphatases in the DNA damage response and cancer. Oncogene 29: 5977-5988.
- Peng A, Yamamoto TM, Goldberg ML, Maller JL. (2010) A novel role for greatwall kinase in recovery from DNA damage. Cell Cycle 9: 4364-4369.
- Peng A, Lewellyn AL, Maller JL. (2008) DNA damage signaling in early xenopus embryos. Cell Cycle 7:3-6.
- Peng A, Lewellyn AL, Maller JL. (2007) Undamaged DNA transmits and enhances DNA damage checkpoint signals in early embryos. Mol Cell Biol 27:6852-6862.
- Peng A, Chen PL. (2005) NFBD1/MDC1 mediates ATM- and Rad3-related-dependent DNA damage response. Cancer Res.65:1158-1163.
- Polci R, Peng A, Chen PL, Riley DJ, Chen Y. (2004) NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response. Cancer Res 64:8800-8803.
- Peng A, Chen PL. (2003) NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage. J Biol Chem 278:8873-8876.