Benjamin Ping-Chi Chen

ContactUniversity of Texas Southwestern Medical Center

Department of Radiation Oncology, Molecular Radiation Biology Division

2201 Inwood Rd., Room NC7.502, Dallas, TX75390

Tel: 214-648-1263, Fax: 214-648-5995

Email:

Education

1983-1987 B.S., Dept. Entomology, National Taiwan University, Taiwan.

1991-1996 Ph. D., Ohio State Biochemistry Program, the Ohio State University.

Academic Appointment

1996 - 1997Postdoctoral Fellow, School of Medicine, UC San Diego.

1997 - 1998Postdoctoral Fellow, Dept. Bioengineering, UC San Diego.

1998 - 2001Assistant Project Scientist, Dept. Bioengineering, UC San Diego.

2001 - 2004 Biology Scientist, Life Sciences Division, Lawrence Berkeley Laboratory.

2004 to dateAssistant Professor, Dept. Radiation Oncology, UT Southwestern.

Teaching

  1. Summer undergraduate research fellowship (SURF) program.
  2. Radiation Biology course for Residents, Dept. Radiation Oncology (2006 to date).
  3. UTSW Graduate School of Biomedical Sciences. Literature Critiques & Discussion in Genetics (2006 to date).

Membership in Professional Organizations

Radiation Research Society

Society for Chinese Bioscientists in America

American Association for the Advancement of Science

Patent

United States Patent 7491804. Title “DNA dependent protein kinase catalytic subunit phosphorylation sites and antibodies thereto”.

Animal Transgenic Training

1998 Animal Technology Institute Taiwan, Animal Science division.

Grants and awards

NIH, RO1CA134991, 04/01/2009-03/31/2014

Title: Function of WRN in Response to DNA Double Strand-Breaks

Role: Co-Principal Investigator (PI: Chen, David J.)

NIH, R01-CA050519, 1/1/2008-12/31/2011

Title: Roles of DNA-PKcs in DNA Double Strand Break Repair

Role: Co-Principal Investigator (P.I. David J. Chen)

NASA, NNX07AP84G, 09/1/2007-8/31/2011

Title: The Impact of HZE Particles on Adult Neural Stem Cells and Neurogenesis

Role: Principal Investigator (Co-PI: Eisch, Amelia)

NIH, MERIT award, R37-CA050519, 10/1/2004-12/31/2007

Title: Roles of DNA-PKcs in DNA Double Strand Break Repair

Role: Co-Principal Investigator (P.I. David J. Chen)

NIH, R01-CA086936, 5/28/2002 - 3/31/2007

Title: Transgenic Mouse Models: DNA Damage Sensing and Signaling

Role: Co-Investigator (P.I. David J. Chen)

NIH, RFA PAR-05-060, 9/16/2005 - 9/15/2006

Title: Screening of DNA-PKcs Autophosphorylation Blockers via Cell-Based Approach.

Role: Principle Investigator

NIH, R01HL62747-01A1, 2/8/2000-1/31/2004

Title: Mechanisms of Reperfusion Induction of ROS and IKK

Role: Co-Investigator (P.I., Shu Chien)

NIH, R01 HL64382-01, 9/28/1999-8/31/2004

Title: Molecular Basis of Endothelial Remodeling by Flow

Role: Co-Investigator (P.I., Shu Chien)

Publications

  1. Wiweka Kaszubska, Rob Hooft van Huijsduijnen, Paola Ghersa, Anne-Marie DeRaemy-Schenk, Benjamin P.C. Chen, Tsonwin Hai, John F. DeLamarter and James Whelan. 1993. Cyclic AMP-independent ATF family members interact with NF-kB and function in the activation of the E-selectin promoter in Response to cytokine. Mol. Cell. Biol. 13: 7180-7190.
  2. Benjamin P.C. Chen and Tsonwin Hai. 1994. Expression vector for affinity purification and radiolabeling of proteins using Escherichia coli as host. Gene 139:73-75.
  3. Benjamin P.C. Chen, Guosheng Liang and Tsonwin Hai. 1994. ATF3 and ATF3∆zip: Transcriptional repression versus activation by alternatively spliced isoforms. J. Biol. Chem. 269: 15819-15826.
  4. Benjamin P.C. Chen, Curt D. Wolfgang, and Tsonwin Hai. 1996. Analysis of ATF3: A transcription factor induced by physiological stresses and modulated by gadd153/Chop10. Mol. Cell. Biol. 16: 1157-1168.
  5. Curt D. Wolfgang, Benjamin P.C. Chen, Jennifer L. Martindale, Nikki J. Holbrook, and Tsonwin Hai. 1997. gadd153/Chop10, a potential target gene of the transcriptional repressor ATF3. Mol. Cell. Biol. 17: 6700-6707.
  6. Song Li, Benjamin P.C. Chen, Nobuyoshi Azuma, Ying-Li Hu, Steven Z. Wu, Bauer E. Sumpio, John Y-J Shyy, and Shu Chien. 1999. Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. J. Clin. Invest. 103: 1141-1150.
  7. Kurt Lin, Pin-Pin Hsu, Benjamin P. Chen, Suli Yuan, Shunichi Usami, John Y-J. Shyy, Yi-Shuan Li and Shu Chien. 2000. Molecular Mechanism of Endothelial Growth Arrest by Laminar Shear Stress. Proc Natl Acad Sci U S A. 97: 9385-9389.
  8. Benjamin P.C. Chen, Yi-Shuan Li, Yihua Zhao, Kuang-Den Chen, Song Li, Jianmin Lao, Suli Yuan, John Y-J. Shyy, and Shu Chien. 2001. DNA Microarray Analysis of Gene Expression in Endothelial Cells in Response to 24-hour Shear Stress. Physiol Genomics 7:55-63.
  9. Sandeep Burma, Benjamin P. Chen, Michael Murphy, Akihiro Kurimasa, and David J. Chen. 2001. ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks. J. Biol. Chem. 276: 42462-42467.
  10. Yi Liu, Benjamin P.C. Chen, Yi, Zhu, Michael B. Stemerman, Shu Chien, and John Y-J. Shyy. 2002. Shear Stress Activation of SREBP1 in endothelial cells is mediated by integrins. Arterioscler. Thromb. Vasc. Biol. 22: 76-81. (Y.L. and B.P.C. contributed equally to this work).
  11. Hui Miao, Song Li, Ying-Li Hu, Suli Yuan, Yihua Zhao, Benjamin P.C. Chen, Wima Puzon-McLaughling, Takehiko Tarui, John Y-J. Shyy, Yoshikazu Takada, Shunichi Usami, Shu Chien. Differential regulation of Rho GTPases by beta1 and beta3 integrins: the role of an extracellular domain of integrin in intracellular signaling. J. Cell Sci 115: 2199-2206.
  12. Doug W. Chan, Benjamin P.C. Chen, Sheela Prithivirajsingh, Akihiro Kurimasa, Michael D. Story, Jun Qin, and David J. Chen. 2002. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Gene & Dev 16:2333-2338. (D.W.C. and B.P.C. contributed equally to this work).
  13. Yihua Zhao, Benjamin P.C. Chen, Hui Miao, Suli Yuan, Yi-Shuan Li, Yingli Hu, David M Rocke, and Shu Chien. 2002. Improved Significance for DNA Microarray Data: Temporal Modulation of Endothelial Gene Expression by Shear Stress. Physiol Genomics 12:1-11.
  14. Song Li, Jianmin Lao, Benjamin P.C. Chen, Yi-Shuan Li, Yihua Zhao, Julia Chu, Kuang-Den Chen, Tsui-Chun Tsou, Konnan Peck, and Shu Chien. 2003. Genomic Analysis of Smooth Muscle Cells in Three-Dimensional Collagen Matrix. FASEB J. 17:97-9.
  15. Jihe Zhao, Z. Christine Bian, Kristine Yee, Benjamin P.C. Chen, Shu Chien, and Jun-Lin Guan. 2003. Identification of Transcription Factor KLF8 as a Downstream Target of Focal Adhesion Kinase in Its Regulation of Cyclin D1 and Cell Cycle Progression. Mol. Cell 11:1503-15
  16. Song Li, James Jaehyun Moon, Hui Miao, Gang Jin, Benjamin P.C. Chen, Suli Yuan, Yingli Hu, Shunichi Usami, and Shu Chien. 2003. Signal transduction in matrix contraction and the migration of vascular smooth muscle cells in three-dimensional matrix. J Vasc Res. 40:378-88.
  17. Thomas Wechsler, Benjamin P.C. Chen, Ryan Harper, Keiko Morotomi-Yano, Betty C.B. Huang, Katheryn Meek, James E. Cleaver, David J. Chen, and Matthias Wabl. 2004. DNA-PKcs function regulated specifically by protein phosphatase 5. Proc Natl Acad Sci U S A. 101-1247-52.
  18. Utz Herbig, Wendy A. Jobling, Benjamin P.C. Chen, David J. Chen, and John M. Sedivy. 2004. Telomere Shortening triggers Replication Senescence of Human Cells Through a Signaling Pathway Involving ATM, p53 and p21CIP1 but not p16ink4a. Mol. Cell 14:501-13.
  19. Hao Luo, Doug W. Chan, Tao Yang, Maria Rodriguez, Benjamin P.C. Chen, Mei Leng, Jung-Jung Mu, David Chen, Zhou Songyang, Yi Wang and Jun Qin. 2004. A link between DNA Single Strand Break Repair and Ataxia with Oculomotor Apraxia. Mol. Cell. Biol. 24: 8356-8365.
  20. Zhenkun Lou, Benjamin P.C. Chen, Aroumougame Asaithamby, Katherine Minter-Dykhouse, David J. Chen, and Junjie Chen. 2004. The H2AX-MDC1 Pathway Regulates DNA-PK Localization and Autophosphorylation in Response to DNA Damage. J. Biol. Chem. 279: 46359-62.
  21. Benjamin P.C. Chen, Doug W. Chan, Junya Kobayashi, Sandeep Burma, Aroumougame Asaithamby, Keiko Yano, Elliot Botvinick, Jun Qin, and David J. Chen. 2005. Cell Cycle Dependence of DNA-PK phosphorylation in Response to DNA Double Strand Breaks. J. Biol. Chem. 280: 14709-15. (BPC corresponding author).
  22. Michal Shuker, Eitan Zlotorynski, Michal Goldberg, Ayelet Rahat, Carlos le Sage, Benjamin P.C. Chen, David J. Chen, Reuven Agami, Batsheva Kerem. 2005. Homologous recombination and non-homologous end joining double-strand break repair pathways regulate fragile site stability. Gene & Dev. 19:2715-26.
  23. Shahnaz T. Al Rashid, Graham Dellaire, Andrew Cuddihy, Farid Jalali, Mita Vaid, Carla Coackley, Melvyn Folkard, Yang Xu, Benjamin P.C. Chen, David J. Chen, Lothar Lilge, Kevin M. Prise, David P. Bazett Jones, and Robert G. Bristow. 2005. Evidence for the Direct Binding of Phosphorylated p53 to Sites of DNA Breaks In vivo. Cancer Res. 65: 10810-21.
  24. Bipasha Mukherjee, Chase Kessinger, Junya Kobayashi, Benjamin P.C. Chen, David J. Chen, Aloke Chatterjee, and Sandeep Burma. 2006. DNA-PK phosphorylates Histone H2AX During Apoptosis DNA Fragmentation in Mammalian Cells. DNA Repair. 5:575-590.
  25. Sandeep Burma, Benjamin P.C. Chen, David J. Chen. 2006. Role of non-homologous end joining (NHEJ) in maintaining genomic integrity. DNA Repair. 5: 1042-8.
  26. Hirohiko Yijima, Kyung-Jong Lee, and Benjamin P.C. Chen. 2006. ATR-dependent DNA-PKcs phosphorylation in response to UV-induced replication stress. Mol. Cell. Biol. 26:7520-8.
  27. Sandeep Burma, Benjamin P.C. Chen, David J. Chen. 2007. Chapter 6: Role of Non-homologous End Joining in Repair of DNA Double-Strand Break. Book title: DNA Repair, Genetic Instability, and Cancer.
  28. Longhou Fang, YiGuo Wang, Dan Du, Guang Yang, Tim Tak Kwok, Siu Kai Kong, Benjamin Chen, David J Chen, Zhengjun Chen. 2007. Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair. Cell Research. 17:100-116.
  29. Benjamin P.C. Chen, Naoya Uematsu, Junya Kobayashi, Yaniv Lerenthal, Hirohiko Yajima, Andrea Krempler, Markus Lobrich, Yossi Shiloh, David J. Chen. 2007. ATM is essential for phosphorylation of DNA-PKcs at T2609 cluster upon DNA double strand break. J. Biol. Chem. 282: 6582-6587.
  30. Naoya Uematsu, Eric Weterings, Ken-ichi Yano, Keiko Morotomi-Yano, Burkhard Jakob, Gisela Taucher-Scholz, Pierre-Olivier Mari, Dik C. van Gent, Benjamin P. C. Chen, and David J. Chen. 2007. Autophosphorylation of DNA-PKcs regulates its dynamics at DNA double-strand breaks. J. Cell Biol. 177:219-29.
  31. Amit K. Das, Benjamin P. Chen, Michael D. Story, John D. Minna, David J. Chen, and Chaitanya S. Nirodi. 2007. Somatic mutations in the tyrosine kinase domain of EGFR abrogate EGFR-mediated radio-protection in non-small cell lung carcinoma. Cancer Res. 67: 5267-74.
  32. Elisabeth Kodym, Reinhard Kodym, Benjamin P. Chen, David J. Chen, Keiko Morotomi-Yano, Hak Choy, and Debabrata Saha. 2007. DNA-PKcs Dependent Modulation of Cellular Radiosensitivity by a Selective Cyclooxygenase-2 Inhibitor. Int. J. Radiation Oncology Biol. Phys. 69:187-93.
  33. Hirohiko Yajima, Kyung-Jong Lee, Shichuan Zhang, Junya Kobayashi, and Benjamin P.C. Chen. 2008. DNA Double Strand Break Formation upon UV-Induced Replication Stress Activates ATM and DNA-PKcs Kinases. J. Mol. Biol. 385:800-810.
  34. Mingan Shi, Carolyn J. Vivian, Kyung-Jong Lee, Chunmin Ge, Keiko Morotomi-Yano, Claudia Manzl, Florian Bock, Shigeo Sato, Chieri Sato, Ruihong Zhu, Selene K. Swanson, Michael P. Washburn, David J. Chen, Benjamin P. C. Chen, Andreas Villunger, Laurence Florens, Chunying Du. 2009. DNA-PKcs-PIDDosome: A Nuclear Caspase-2-Activating Protein Complex Required for a G2/M DNA Damage Checkpoint and DNA Nonhomologous End-Joining. Cell. 136:508-20.
  35. Junya Kobayashi, Hiroshi Tauchi, Benjamin P.C. Chen, Sandeep Bruma, Satoshi Tashiro, Shinya Matsuura, Keiji Tanimoto, David J Chen, and Kenshi Komatsu. 2009. Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1. Biochem Biophys Res Commun. 380:752-7.
  36. Angela Y.J. Li, Lee Ming Boo, Shih-Ya Wang, Xu Li, H. Helen Lin, Clay C.C. Wang, Yun Yen, Benjamin P.C. Chen, David J. Chen, and David K. Ann. 2009. Suppression of Non-Homologous End Joining Repair by Overexpression of HMGA2. Cancer Res. 69:5699-706.
  37. Meena Shrivastav, Cheryl A. Miller, Leyma P. De Haro, Stephen T. Durant, Benjamin P.C. Chen, David J. Chen, and Jac A. Nickoloff. 2009. DNA-PKcs and ATM Co-Regulate DNA Double-Strand Break Repair. DNA Repair. 6:920-9.
  38. Debabrata Saha, Linda Watkins, Yi Yin, Philip Thorpe, Michael D. Story, Kwang Song, Pavithra Raghavan, Robert Timmerman, Benjamin Chen, John D. Minna, and Timothy D. Solberg. 2010. An Orthotopic Lung Tumor Model for Image-Guided Stereotactic Irradiation in Rats. Radiation Research accepted.
  39. Cristiana Iosef, Gregory Vilk, Theofanis Gkourasas, Kyung-Jong Lee, Benjamin P.C. Chen, Ping Fu, Leon A. Bach, Gilles Lajoie, Madhulika B. Gupta, Shawn S. C. Li and Victor K. Han. 2010. Insulin-like growth factor binding protein 6 (IGFBP-6) interacts with DNA-end binding protein Ku80 to regulate cell fate. Cellular Signalling accepted.
  40. Hatsumi Nagasawa, John B. Little, Yu-Fen Lin, Sairei So, Akihiro Kurimasa, Yuanlin Peng, John R. Brogan, David J. Chen, Joel S. Bedford, and Benjamin P. C. Chen. Differential role of DNA-PKcs phosphorylations and kinase activity in radiosensitivity and spontaneous chromosomal numerical instability. Radiation Research accepted.
  41. Shichuan Zhang, Hirohiko Yajima, HoangDinh Huynh, Elsa Callen, Junke Zheng, Yu-Fen Lin1, Michael Story, Hua-Tang Chen, Nancy Wong, Samuel Bunting, Eric Gapud, Barry P. Sleckman, André Nussenzweig, Cheng Cheng Zhang, David J. Chen, Benjamin P.C. Chen. Severe anemia and stem cell failure in DNA-PKcs mutant mice associated with deficiencies in multiple DNA repair pathways. Manuscript submitted.
  42. Nathan A. DeCarolis, H. Francisca Ahn, Diane L. Lagace, Jessica L. Ables, Benjamin P.C. Chen, Amelia J. Eisch. Running after irradiation ameliorates the proliferation deficit but not the nestin-expressing Type-1 cell deficit in the adult hippocampal subgranular zone. Manuscript submitted.
  43. Kyung-Jong Lee, Yu-Fen Lin, Hirohiko Yajima, Kazi R. Fattah, Han-Yi Chou, Sheng-Chung Lee, and Benjamin P.C. Chen. Mitotic Activation of DNA Dependent Protein Kinase Modulates Microtubule Dynamics and Chromosome Segregation. Manuscript submitted.

Invited Speech

  1. The First International Conference on Frontiers in Biomedical and Environmental Health Sciences from Molecular and Systems Biology to Human Diseases. Wuhan, China, June 26-30, 2006. Title: ATR-dependent DNA-PKcs phosphorylation in response to UV-induced replication stress.
  2. 2006 International Workshop on Ataxia-Telangiectasia (A-T) and ATM. Banff, Canada, September 8-12, 2006. Title: ATR-dependent DNA-PKcs phosphorylation in response to UV-induced replication stress.
  3. Pathology Grand Rounds, University of Iowa, September 21, 2006. Title: The Significance of DNA-PKcs Phosphorylation in response to DNA Double-Strand Breaks and Replication Stress.
  4. 10th International Wolfsberg Meeting, Wolfsberg, Switzland, May 12-14, 2007. Title: DNA-PKcs dynamics and phosphorylation at DSBs in vivo.
  5. 9th Annual Midwest DNA Repair Symposium, Columbus, Ohio. May 19-20, 2007. Title: DNA-PKcs Phosphorylation mediated by ATM and ATR kinases.
  6. EMS 38th Annual Meeting, Atlanta, Georgia. October 20-24, 2007. Title: Late activation of ATM and DNA-PKcs kinases upon UV-induced replication stress.
  7. Stowers Institute, Kansas City, Missouri. December 13-14, 2007. Title: Phosphorylation of DNA-PKcs in response to DNA double strand break and replication stress.
  8. 2nd International Conference on Frontiers in Biomedical and Environmental Health Sciences: DNA Repair and Cancer Biology. April 16 – 20, 2008. Hangzhou, China. Title: DNA-PKcs Phosphorylation at Thr2609 Cluster Region is Required for Maintenance of Haematopoietic Stem Cells.
  9. Gordon Research Conference: Mammalian DNA Repair. February 8-13, 2009. Ventura, CA. Title: DNA-PKcs Phosphorylation in DNA Repair and in Haematopoietic Stem Cells Maintenance.
  10. Beijing Institute of Radiation Medicine, Beijing, China, March 23-24, 2009. Title: DNA-PKcs Phosphorylations in DNA Damage Responses and Cell Cycle Progression.
  11. Institute of Zoology, Chinese Academy of Sciences, Beijing, China, March 25, 2009. Title: DNA-PKcs Phosphorylations in DNA Damage Responses and Haematopoietic Stem Cells Maintenance.
  12. 12th Society of Chinese Bioscientists in America (SCBA) International Symposium, Academia Sinica, Taipei, Taiwan, June 14-18, 2009. Title: Activation and Involvement of DNA-PKcs Kinase in Cell Cycle Progression through Mitosis.
  13. 55th Annual Meeting of the Radiation Research Society, Savannah, George. Oct 4-7, 2009. Title: Impact of 56Fe Particle Irradiation on Adult Neural Stem Cells In Vivo”.
  14. The International Ataxia-Telangiectasia Workshop 2010. Redondo Beach, California, April 11-14, 2010. Title: Severe Anemia and Hematopoietic Stem Cell Failure in DNK-PKcs Mutant Mice Associated With Deficiencies in Multiple DNA Repair Pathways.
  15. The International Conference on Biomedical and Environmental Sciences & Technology: DNA Repair and Cancer Intervention (icBEST). Beijing, China, May 9-12, 2010. Title: Severe Anemia and Hematopoietic Stem Cell Failure in DNK-PKcs Mutant Mice Associated With Deficiencies in Multiple DNA Repair Pathways.

Grant Reviewer

  1. The Netherlands Organization for Health Research and Development (ZonMw), 2006 Cycle.
  2. Association for International Cancer Research (AICR), UK. 2008 Cycle.
  3. Pennsylvania Department of Health for the Pennsylvania Final Performance Review. 06-07 Cycle A & B, 07-08 Cycle B, 08-09 Cycle A.

Journal Reviewer

Cancer Research

Carcinogenesis

Cell Biology & Toxicology

Cell Cycle

J. Biological Chemistry

J. Cell Physiology

J. Investigative Dermatology

J. Molecular Biology

J. Proteome Research

Molecular Cellular Biochemistry

Nucleic Acids Research

PLoS One

Oncogene

Radiation Research