Dietmar J. Kappes, PhD

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Director, Transgenic Mouse Facility

Professor, Blood Cell Development and Function Program

Research Program

Nuclear Dynamics and Cancer

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

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

People

Hua, Xiang

Manager, Transgenic Mouse Facility

R293

728-2182

[email protected]
Ge, Lu,

Scientific Tech I

R293

728-2182,

[email protected]
Hu, Taishan , PhD

Assist. Research Professor

R293

728-5375

[email protected]
Li, Qin, MD PhD

Postdoctoral Research Associate

R293,

728-5375
Mookerjee-Basu, Jayati, PhD

Postdoctoral Associate

R293

728-5375

Research Facility

Transgenic Mouse Facility

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.

Selected Publications

Basu J., Reis B.S., Peri S., Zha J., Hua X., Ge L., Ferchen K., Nicolas E., Czyzewicz P., Cai K.Q., Tan Y., Fuxman Bass J.I., Walhout A.J.M., Grimes H.L., Grivennikov S.I., Mucida D., Kappes D.J., Essential role of a thpok autoregulatory loop in the maintenance of mature cd4(+) t cell identity and function. Nat Immunol. 22(8): 969-982, 2021. PMC8887595. https://www.ncbi.nlm.nih.gov/pubmed/34312548.

Fahl SP, Coffey F, Kain L, Zarin P, Dunbrack RL, Jr., Teyton L, Zuniga-Pflucker JC, Kappes DJ, Wiest DL. Role of a selecting ligand in shaping the murine gammadelta-TCR repertoire. Proceedings of the National Academy of Sciences of the United States of America, 115(8):1889-94, 2018. PMC5828614

Fahl SP, Coffey F, Kain L, Zarin P, Dunbrack RL, Jr., Teyton L, Zuniga-Pflucker JC, Kappes DJ, Wiest DL. Role of a selecting ligand in shaping the murine gammadelta-TCR repertoire. Proc Natl Acad Sci U S A, 115(8):1889-94, 2018. PMC5828614

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

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

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

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

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

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

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... Expand

Additional Publications

My NCBI

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