Contact Information

Research

Research
 
The major focus of Dr. Shen’s group is on the mechanistic roles of nucleases in DNA replication in the nucleus and mitochondrion and in cellular responses and repair of DNA damage induced by environmental insults such as ionizing radiation. The team employs multiple approaches such as crystallographic, biochemical, yeast and mouse genetic techniques to study these phenomena. His group co-discovered the FEN1 structure specific nuclease family important in DNA replication, repair, and apoptosis DNA fragmentation. Based on comprehensive structural and functional analyses and mutation screenings, Dr. Shen’s group has established a series of knock in mouse models to elucidate etiology of FEN1-based cancers. More recently, he was the first to establish a mouse model for another structure-specific nuclease DNA2 and identified its major role in telomere stability and cancer. His group also made the initial observation on its mitochondrion localization and its mutations in mitochondrion based myopathy patients. In collaboration with the Lung Cancer Program's investigators Dan Raz, M.D., Karen Reckamp, M,D., and Jae Kim, M.D., a subgroup of the Shen laboratory led by Li Zheng, Ph.D., is developing triptolide-based therapeutic regimens against lung cancer employing the established mouse models.
 
Also in Dr. Shen's laboratory, Fong Fong Chu, Ph.D. works to understand how oxidative damages contribute to inflammatory diseases and cancers. Specifically, her studies aim to understand the balance between pro- and anti-oxidants in the gut. She has characterized a model of inflammatory bowel disease (IBD) in mice deficient in two selenium-dependent, H2O2-reducing glutathione peroxidases (GPxs).  Similar to Crohn’s disease and ulcerative colitis (human IBD), she found mouse genetic background, diets and gut microbes each play a significant role on disease severity in the GPx1/2-double knockout (DKO) mice. Currently, she is focusing on two major gut epithelial oxidases, NOX1 and DUOX2, to determine whether they produce sufficient oxidants to activate the pro-inflammatory responses.

Recent Publications

Recent Publications
 
Zheng, L., Dai, H., Zhou, M., Li, M., Singh, P., Qiu, J., Tsark, W., Huang, Q., Kernstine, K.K., Zhang, X., Lin, D, and Shen, B. (2007) Fen1 mutations results in autoimmunity, chronic inflammation, and cancers.  Nature Medicine, 13, 812-819.
 
Zheng L., Zhou, M., Dai, H., Guo, Z., Lu, H., Qiu, J., Bogenhagen, and Shen, B. (2008) Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates, in complex with polymerase  and flap endonuclease 1.  Mol.  Cell, 32, 325-336.
 
Lu, H., Gao, G., Xu, G., Fan, L., Yin, L., Shen, B., and Hua, Y. (2009) Deinococcus radiodurans PprI switches on DNA damage-response and cellular survival networks after radiation damage. Mol. Cell. Proteomics, 8, 481-494.
 
Finger, L.D., Blanchard, M.S., Theimer, C.A., Sengerova, B., Singh, P., Chavez, V., Liu, F., Grasby, J.A., and Shen, B. (2009) The 3’-flap pocket of human flap endonuclease 1 is critical for substrate binding and catalysis. J. Biol. Chem. 284, 22184-22194.
 
Guo, Z.,  Zheng, L., Xu, H., Dai, H., Zhou, M., Pascua, M. R., Chen, Q. M.,  and Shen, B. (2010) Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding, Nature Chem. Biol. 6, 766-773. DOI: 10.1038
 
Tsutakawa, S.E., Classen, S., Chapados, B.R., Arval, A., Finger, L.D., Guenther, G., Tomlinson, C.G., Thompson, P., Sarker, A.H., Shen, B., Cooper, P.K., Grasby, J.A., and Tainer, J.A. (2011) Human flap endonuclease structures, DNA double base flipping and a unified understanding of the FEN1 superfamily. Cell, 145, 198-211.
 
Zheng, L., Dai, H., Zhou, M., Li, X., Guo, Z., Wu, X., Wu, J., Wang, C., Zhong, J., Huang, Q., Garcia-Aguilar, J., Pfeifer, G., and Shen, B. (2012) Polyploidy rewires DNA damage response and repair network to overcome DNA replication stresses and to escape cellular senescence, Nature Communications, 3, 815-826.
 
Guo, Z., Kanjanapangka, J., Liu, N., Liu, S., Liu, C., Wu, Z., Wang, Y., Loh, T., Kowolik, C., Jamsen, J., Zhou, M., Truong, K., Chen, Y.,  Zheng, L., Shen, B. (2012), Sequential Posttranslational modifications program FEN1 degradation during cell-cycle progression. Molecular Cell, 47, 444-456.
 
Lin, Y., Yang, Y., Li, W., Chen, Q., Li, J., Pan, X., Zhou, L., Liu, C., Chen, C., He, J., Cao, H., Yao, H., Zheng, L., Xia, Z., Ren, J., Xiao, L., Li, L., Shen, B*., Zhou, H*., Wang, Y*. (2012) Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells. Molecular Cell, 48, 627-640. *Co-corresponding authors.
 
Ronchi, D., Di Fonzo, A., Lin, W., Bordoni, A., Liu, C., Fassone, E., Pagliarani, S., Rizzuti, M., Zheng, L., Filosto, M., Ferrò, M. T., Ranieri, M., Magri, F., Corti, S., Sciacco, H. Li, Y.-C. Yuan, M., Moggio, M., Bresolin, N., Shen, B.*, and Comi, G. P*. (2013). Mutations in DNA2 link progressive myopathy with mitochondrial DNA instability. American Journal of Human Genetics, 92, 293-300. Co-corresponding authors.
 
Lin, W., Sampathi, S., Dai, H., Liu, C., Zhou, M., Hu, J., Huang, Q., Campbell, J., Zheng, L., Chai, W., and Shen, B. (2013). Mammalian DNA2 helicase/nuclease cleaves G-quadruplex and is required for telomere integrity. EMBO J., 32, 1425-1439.
 

Laboratory

The Shen group, 12/12/2013
The Laboratory
 
The Shen laboratory has carried out various major National Institutes of Health-funded projects. The laboratory has active and long term collaborations with Dr. John Tainer, Berkeley and Dr. Judith Campbell, Caltech. The group also collaborates with Dr. Yuejin Hua of Zhejiang University, China, in the study of radiation-induced DNA damage responses in Deinococcus radiodurans.
 
The laboratory is located in the Beckman Research Institute at City of Hope in Duarte, California. Duarte is in the northeast suburbs of Los Angeles, just outside Pasadena, nestled in the foothills of the San Gabriel mountains. We're close to all of the entertainment and scenic attractions Southern California has to offer, yet far enough removed from the big city buzz. Take a half hour drive to the beach, or an hour and a half to local skiing. The medical center and Beckman Research Institute are situated on a beautiful, 112-acre campus, and our lab is housed in the Kaplan-Black Research Building.

Approximately 25 NCI-supported core facilities are available for biomedical research in City of Hope as a Comprehensive Cancer Center research facility. These include: microarray, mass-spectroscopy/protein sequencing, DNA sequencing, oligonucleotide & peptide synthesis, phosphor- and fluoro-imaging, histology/histochemistry, frozen tumor bank, time-lapse videography, confocal and electron microscopies, cytogenetics, NMR, flow-cytometry, molecular modeling, transgenic mice, and animal care.

An active Postdoctoral Association (PDA) and the Office for Postdoctoral Training promote interaction between the Institute and postdoctoral fellows and graduate students, to help to ensure that their transition is smooth and their time here is as fulfilling as possible.
 

Education and Experience

Education
  • 1883: Zhejiang University, Hangzhou, P.R. China B.S. Biology
  • 1991: Kansas State University, Manhattan, Kansas Ph.D. Molecular Genetics
  • 1991-1994: University of California, Irvine, Irvine, CA Postdoctoral Fellow - Molecular Biology and Biochemistry
  • 1994-1996: Los Alamos National Laboratory, Los Alamos, NM Postdoctoral Fellow - Molecular Biology and Biochemistry
     

Positions and Honors

Positions

  • 1996-2000: Assistant Professor, Department of Cell and Tumor Biology, Beckman Research Institute, and Graduate School in Biological Sciences; Member, NCI-designated Comprehensive Cancer Center, City of Hope, Duarte, CA
  • 2000-2004: Associate Professor, Division of Molecular Medicine, Beckman Research Institute, and Graduate School in Biological Sciences; Member, NCI-designated Comprehensive Cancer Center, City of Hope, Duarte, CA
  • 2004-2012: Professor and Director, Division of Radiation Biology, Associate Chair, Department of Cancer Biology, Beckman Research Institute, and Irell & Manella Graduate School in Biological Sciences; Member, NCI-designated Comprehensive Cancer Center, City of Hope, Duarte, CA
  • 2011-Present: Member and Co-leader, Molecular Oncology Program, NCI-designated Comprehensive Cancer Center, City of Hope Duarte, CA
  • 2012-Present: Professor and Chair, Department of Radiation Biology, Beckman Research Institute; Irell & Manella Graduate School in Biological Sciences; City of Hope, Duarte, CA

 

Other Experiences and Professional Memberships
  • 1989-Present: Member, American Association for the Advancement of Science
  • 1996-Present: Member, American Society of Cancer Research
  • 1997-Present: Member, American Society of Radiation Research
  • 2002-Present: Member, American Society of Biochemistry and Molecular Biology
  • 2000: Ad hoc Member, NIH Experimental Therapeutics I Study Section
  • 2002: Panel Reviewer, DOD Breast Cancer Research Program
  • 2002-2006: Member, NIH Radiation Therapeutics and Biology (RTB) Study Section
  • 2007-Present: Ad Hoc Member, NIH Cancer Etiology Study Section

 

Honors

  • 1982: “Three Excellence” award for excellence in moral, academic and physical education, Zhejiang University
  • 1984: Teaching Excellence Award, Education Committee, Zhejiang Province, P.R. China
  • 1989: The Honor Society of PHI KAPPA PHI, Kansas State University Chapter, Manhattan, KS.
  • 2011: City of Hope Portrait Gallery of Scientific Achievement