Research Department

Cancer Immunology and AIDS

Area of Research

Lymphocyte Differentiation, Tolerance

Biography

Dr. von Boehmer received his MD in 1968 from the University of Munich, Germany, and his PhD in 1974 from Melbourne University, Australia. He has been a permanent member of the Basel Institute of Immunology, Switzerland, professor of immunology in Basel and in Paris, as well as director of INSERM Research Unit 373 in Paris. He joined DFCI in 1999 and conducts basic and translational research in lymphocyte development and disease models of diabetes and cancer.

Recent Awards

• Boston Area Diabetes Endocrinology Research Center Award, 2011
• Sherman Fairchild Foundation Research Award, 2004
• NIH Merit Award, 2003
• Honorary Medical Degree, Munich, 2002
• Koerber Prize for European Science, 1997
• Paul Ehrlich Prize, 1993
• Avery-Landsteiner Prize, 1990
• Louis Jeantet Prize, 1990

Research

The immune system needs to be effective in defending the organism against invading microorganisms and malignant transformation. At the same time, autoimmune reactions against normal constituents of the body must be avoided. T lymphocytes play a crucial role in self-nonself discrimination, and therefore their development, selection, and reactivity are of considerable interest in both basic and translational research.

T lymphocyte development and selection

Our laboratory focuses on the development of T lymphocytes from pluripotent hemopoietic stem cells. The lab has uncovered the major principles of positive and negative lymphocyte selection and discovered the pre-T cell receptor (TCR). We have elucidated the role of the pre-TCR in αβ lineage commitment. We have defined the parameters of the intrathymic and extrathymic generation of regulatory T cells.

Autoimmune diabetes

We have found that insulin is a crucial antigen in the initiation of type 1 diabetes. We have developed a vaccination protocol that prevents type 1 diabetes and are beginning to translate the studies from a mouse system to the human.

Cancer

Immune responses to cancer-associated antigens are usually weak, though the reasons for this are largely unknown. We have shown in animal models that growing tumors can effectively escape tumor-specific T cells. In addition, in collaboration with the von Andrian lab at the Center for Blood Research (CBR), we have shown that tumor-specific regulatory T cells can interfere with the lysis of tumors by CD8 T cells. We have studied the mechanisms of T-ALL generation and discovered miRNA's that act as tumor suppressors.

Select Publications

• Sicinska E, Aifantis I, Le Cam L, Swat W, Borowski C, Yu Q, Ferrando AA, Levin SD, Geng Y, von Boehmer H, Sicinski P. Requirement for cyclin D3 in lymphocyte development and T cell leukemias. Cancer Cell 2003;4:451-61.
• Klein L, Khazaie K, von Boehmer H. In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc Natl Acad Sci U S A 2003;100:8886-92.
• Borowski C, Li X, Aifantis I, Gounari F, von Boehmer H. Pre-TCRalpha and TCRalpha are not interchangeable partners of TCRbeta during T lymphocyte development. J Exp Med 2004;199:607-15.
• Jaeckel E, Lipes M, von Boehmer H. Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes. Nat Immunol 2004;5;1028-35.
• Apostolou I, von Boehmer H. In vivo instruction of suppressor commitment in naive T cells. J Exp Med 2004;199;1401-8.
• Kretschmer K, Apostolou I, Hawiger D, Khazaie K, Nussenzweig MC, von Boehmer H. Inducing and expanding regulatory T cells by foreign antigen. Nat Immunol 2005;6:1219-27.
• von Boehmer H. Unique features of the pre-TCRalpha chain: not just a surrogate. Nat Rev Immunol 2005;5:571-7.
• von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat Immunol 2005;6:338- 44.
• Marson, A., Kretschmer, K., Frampton, G.M., Jacobsen, E.S., Polansky, J., MacIsaac, K.D., Levine, S.S, Fraenkel, E., von Boehmer, H., Young, R.A. Foxp3 binds and suppresses transcription of key target genes during T cell stimulation.  Nature 445, 931-5 (2007).
• Li ,X., Gounari,F., Protopopov, F., Khazaie, K. and von Boehmer, H.Oncogenesis of T-ALL and non-malignant consequences of overexpressing intracellular NOTCH1. J. Exp. Med,2008. 205(12):p.2851-61.
• von Boehmer, H and Melchers, F.: Checkpoints in lymphocyte development and autoimmune disease. Nature Immunology 2010 Jan;11(1):14-20.
• Li, X., Sanda, T., Look, A.T., Novina, C.D., and von Boehmer, H. Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL. J. Exp. Med. 208,663 (2011).
• Daniel C, Weigmann B, Bronson R, von Boehmer H. Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong-agonist insulin mimetope. J Exp Med 2011, 208,1501.

Investigators

• Li, Xiaoyu, MD, PhD

Trainees

• Daniel, Carolin, Ph. D
• Gleimer, Michael, Ph. D
• Kreslavsky, Taras, Ph. D
• Schlenner, Susan, Ph. D