Aimin Peng, Ph.D.
UNMC College of Dentistry
40th and Holdrege
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
- 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 in vitro, reconstitutive studies in Xenopus egg extracts with functional investigations in mammalian systems to reveal new insights into these processes.
- 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 systematically investigate this process. We recently reported novel involvement of Greatwall (Gwl) kinase in this pathway, and revealed mutual regulation between Gwl and Polo-like kinase 1 (Plk1). Despite progress, a number of critical questions remain unclear, particularly, how Gwl and Plk1 are re-activated from checkpoint arrest, what are the downstream pathways, and whether these mechanisms contribute to tumorigenesis and chemoresistance, and are thus targetable for cancer therapy? We are continuing our investigation on these important aspects.
- Another focus of our research is protein phosphatase-dependent DDR regulation and its implication for cancer progression and therapy. Recent studies revealed a number of Ser/Thr phosphatase complexes involved in DDR regulation, particularly checkpoint recovery; emerging evidence also suggests that the DDR phosphatases are related to human cancers. We have previously reported a Repo-Man/PP1 complex that dephosphorylates ATM and inhibits ATM-dependent DNA damage signaling. Further efforts to study regulation and potential cancer involvement of Repo-Man/PP1 and other DDR phosphatases will be carried out.
- Nebraska Center for Cellular Signaling, 7/1/2010 to 6/30/2013, Principal Investigator: Keith Johnson, Ph.D.; Project Leader: Aimin Peng, Title: The functions and regulatory mechanisms of a specific protein phosphatase 1 complex in the DNA damage response and cancer progression.
- 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.
- 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. (2005) NFBD1/MDC1 mediates ATM- and Rad3-related-dependent DNA damage response. Cancer Res. 65:1158-1163.
- 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, Lewellyn AL, Maller JL. (2008) DNA damage signaling in early Xenopus embryos. Cell Cycle. 7:3-6.
- 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.
- Wang, L., Fisher, L.A., Wahl III, J.K., Peng, A. (2011) Generation and characterization of monoclonal antibodies against Xenopus Greatwall kinase. Hybridoma (In Press).
- Peng, A., Wang, L., Fisher, L.A. (2011) Greatwall and Polo-like kinase 1 coordinate to promote checkpoint recovery. J Biol Chem (In Press).
- Department of Adult Restorative Dentistry
Department of Dental Hygiene
- Department of Growth & Development
- Department of Oral Biology
- Department of Surgical Specialties