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Dietmar J. Kappes, PhD

About

Director, Transgenic Mouse Facility, Fox Chase Cancer Center:

Professor, Blood Cell Development and Function Program, Fox  Chase Cancer Center, Temple University Health System, Philadelphia, PA

Research Program

Education, Training & Credentials

Educational Background

  • Postdoctoral Fellow, Massachusetts Institute of Technology, Cambridge, MA
  • PHD, Biology, Harvard University, Boston, MA
  • BS, Biology, Chemistry, Harvard University, Boston, MA

Memberships

  • NIH Cellular and Molecular Immunology B Study Section, Standing Member, 2014-2019 
  • Member, American Association of Immunologists
  • Ad hoc Reviewer for Blood, Immunity, Journal of Experimental Medicine, Journal of Immunology, Nature, Nature Immunology, Nature Biotechnology, Science

Honors & Awards

  • Postdoctoral Fellow, Damon Ruyon-Walter Winchell Cancer Research Center - 1988
  • Magna Cum Laude, Harvard University - 1980
Research Profile

Research Program

Research Interests

Regulation of T lymphocyte development, CD4/CD8 lineage commitment and oncogenesis.

  • Analyzing the role of the transcription factor ThPOK in CD4/CD8 lineage choice, and in other hematopoietic processes.
  • Using ZFN and CRISPR approaches to dissect gene regulatory elements in mouse models.
  • Developing novel zebrafish models to elucidate pathways controlling T cell development.
  • Using mouse and zebrafish knockout models to reveal novel mechanisms of oncogenesis.

Lab Overview

My laboratory focuses on understanding the molecular basis of T lymphocyte differentiation and function. In particular, we have employed forward and reverse genetic approaches to elucidate the signaling and transcriptional pathways that regulate these processes. In the course of this work, we have generated numerous new transgenic and knockout mouse models, most recently to assess the specific and redundant roles of ThPOK as a key regulator of T cell development, and to dissect its expression pattern and transcriptional control mechanisms in vivo. We have also initiated work in the zebrafish model, in order to exploit the advantages of this system for genetic screens to identify novel regulators of T cell development and lymphomagenesis. Thus, we have generated new CD4 and ThPOK reporter fish, as well as ThPOK knockout fish, which will both greatly facilitate the study of T helper development and function in zebrafish, and provide the basis for their efficient genetic dissection. Finally, we have discovered a new and so far unrecognized role of ThPOK as an oncogene, using novel animal models that we have generated. This work suggests a widespread and important role of ThPOK in diverse human cancers, and has become a major new focus of my lab. Our work in elucidating the process of CD4/CD8 lineage choice and identifying the key role of ThPOK represents a unique and widely recognized contribution to the field. These findings have important implications for therapeutic manipulation of the cell-based immune system including potentially for cancer treatment 

People

Hua, Xiang

Manager, Transgenic Mouse Facility

Room: R293
728-2182

Ge, Lu,

Scientific Tech I

Room: R293
728-2182,

Hu, Taishan , PhD

Assist. Research Professor

Room: R293
728-5375

Li, Qin, MD PhD

Postdoctoral Research Associate

Room: R293,
728-5375

Mookerjee-Basu, Jayati, PhD

Postdoctoral Associate

Room: R293
728-5375
Publications

Selected Publications

1.         Kappes, D.J., Tonegawa, S.  Surface expression of alternative forms of the TCR/CD3 complex.  Proc. Natl. Acad. Sci. USA 88: 10619-10623, 1991. PubMed

 

2.         Davé, V.P., Cao, Z.-S., Browne, C., Alarcón, B., Fernandez-Miguel, G., Lafaille, J., de la Hera, A., Tonegawa, S., Kappes, D.J.  CD3δ deficiency arrests development of the αβ but not the γδ T cell lineage.  EMBO J. 16: 1360-1370, 1997. PubMed

 

3.         Delgado, P., Fernández, E., Davé, V., Kappes, D.J., Alarcón, B.  CD3δ couples T-cell receptor signalling to ERK activation and thymocyte positive selection.  Nature 406:426-430, 2000.  PubMed

 

4.         Davé, V.P., Allman, D., Keefe, R., Hardy, R.R., Kappes, D.J.  HD mice: a novel mouse mutant with a specific defect in the generation of CD4+ T cells.  Proc. Natl. Acad. Sci. U.S.A. 95:8187-8192, 1998. PubMed

 

5.         Keefe, R., Davé, V.P., Allman, D., Wiest, D., Kappes, D.J.  Regulation of lineage commitment distinct from positive selection.  Science 286:1149-1153, 1999. PubMed

 

6.         He, Xiao, He, Xi, Davé, V.P., Zhang, Y., Hua, X., Xu, W., Roe, B.A., Kappes, D.J.  The zinc finger transcription factor TH POK regulates CD4 versus CD8 T lineage commitment.  Nature 433:826-833, 2005. PubMed

 

7.         Haks, M.C., Lebebvre, J.M., Lauritsen, J.P., Carleton, M., Rhodes, M., Miyazaki, T., Kappes, D.J.*, Wiest, D.L.*  Attenuation of γδ TCR signaling efficiently diverts thymocytes to the αβ lineage.  Immunity 22:595-606, 2005.  *Denotes authors contributed equally. PubMed

 

8.         He, X., Park, K., Wang, H., Zhang, Y., Hua, X., Li, Y., Kappes, D.J.  CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus.  Immunity 28:346-358, 2008. Accepted prior to April 7, 2008. PubMed

 

9.         Engel, I., Hammond, K., Sullivan, B.A., He, X., Taniuchi, I., Kappes, D., Kronenberg, M.  Co-receptor choice by V alpha14i NKT cells is driven by Th POK expression rather than avoidance of CD8-mediated negative selection.  J. Exp. Med. 207:1015-1029, 2010. PMCID: PMC2867285 PubMed

 

10.       Park, K., He, X., Lee, H. O., Hua, X., Li, Y., Wiest, D., Kappes, D.J.  TCR-mediated ThPOK induction promotes development of mature (CD24-) γδ thymocytes.  EMBO J. 29:2329-2341, 2010. PMCID: PMC2910264 PubMed

 

11.       Lee, H.-O., He, X., Mookerjee-Basu, J., Zhongping, D., Hua, X., Nicolas, E., Sulis, M.L., Ferrando, A.A., Testa, J.R., Kappes, D.J. Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas. Proc. Natl. Acad. Sci. U.S.A. 112: 7773-7778, published ahead of print June 8, 2015, doi:10.1073/pnas.1424104112. PMID: 26056302 PubMed

 

Additional Publications

My NCBI