Axel Kallies-Projects

Axel Kallies-Projects

Researcher: 

Projects

Development of a transcriptional framework for peripheral lymphocyte differentiation

This is a central area of interest of my laboratory. We have contributed significantly to three central models of lymphocyte differentiation: 

  • The differentiation of naïve B cells into plasma cells. 
  • The differentiation of naïve CD8+ T cells into effector and memory cells. 
  • The differentiation of thymic derived Foxp3+ regulator T cells (Tregs) 

We are now focusing on the differentiation effector Tregs (eTregs), a previously unknown effector stage of regulatory T cells that we identified and characterised. Furthermore, in collaboration with the B cell program of the Immunology and Molecular Immunology divisions we continue to work on the further development of a transcriptional framework of plasma cell differentiation and malignant transformation of B cells.

 

Metabolic regulation of lymphocyte function and differentiation

We are interested in the role of metabolic regulation of clonal competition and population expansion. We are currently extending these studies to understand the role of cellular metabolism during disease. Deletion or loss of function of antigen-specific T cells is a major problem that prevents efficient clearing of the pathogen during chronic infection with pathogens such HIV or eradication of cancer cells. We have found that metabolic dysregulation is a key feature of failing T cells. We propose that dysregulation of cell metabolism leads to loss of effector function and aborted memory development. Over the next years we wish to test this hypothesis and characterize metabolic dysfunction of lymphocytes during chronic infection, tumour development and identify mechanisms controlling cellular metabolism during chronic stimulation. 

The function of lymphocytes during systemic regulation of metabolism and inflammation

In addition to understanding the role of cellular metabolism during differentiation we have also developed a new research focus on the role of lymphocytes in regulating the systemic state of metabolism. This is based on the observation that specialised lymphocyte populations migrate to the adipose tissue and other non-lymphoid tissues where they alter their environment by regulating the uptake of nutrients, the homeostasis of hormones and the release of inflammatory mediators. Over the next years we aim to identify the molecular requirements for the development of such tissue resident lymphocytes. We have recently submitted the first manuscript related to these studies.

The role T cells in immune surveillance of B cell lymphoma

We aim to bring our expertise in B and T cell biology to the field of leukaemia and lymphoma research. This has resulted in a recent publication on the role of immune surveillance during B lymphoma development. From our results we have formulated our overarching hypothesis that pre-malignant B cells can be identified based on their phenotype and targeted to prevent lymphoma development. We now wish to test this hypothesis and determine the early phenotypic and molecular changes in B cells from which lymphomas arise. This will identify a signature of pre-malignant B cells and mechanisms of immune escape. Furthermore, we will fully elucidate the role of CD8+ T cells in the prevention of B cell lymphoma development with the ultimate aim to translate these findings to human studies to improve disease diagnosis, treatment and prognosis. 

Development of a transcriptional framework for peripheral lymphocyte differentiation

This is a central area of interest of my laboratory. We have contributed significantly to three central models of lymphocyte differentiation: 

  • The differentiation of naïve B cells into plasma cells. 
  • The differentiation of naïve CD8+ T cells into effector and memory cells. 
  • The differentiation of thymic derived Foxp3+ regulator T cells (Tregs) 

We are now focusing on the differentiation effector Tregs (eTregs), a previously unknown effector stage of regulatory T cells that we identified and characterised. Furthermore, in collaboration with the B cell program of the Immunology and Molecular Immunology divisions we continue to work on the further development of a transcriptional framework of plasma cell differentiation and malignant transformation of B cells.

Development of a transcriptional framework for peripheral lymphocyte differentiation

This is a central area of interest of my laboratory. We have contributed significantly to three central models of lymphocyte differentiation: 

  • The differentiation of naïve B cells into plasma cells.
  • The differentiation of naïve CD8+ T cells into effector and memory cells.
  • The differentiation of thymic derived Foxp3+ regulator T cells (Tregs)

We are now focusing on the differentiation effector Tregs (eTregs), a previously unknown effector stage of regulatory T cells that we identified and characterised. Furthermore, in collaboration with the B cell program of the Immunology and Molecular Immunology divisions we continue to work on the further development of a transcriptional framework of plasma cell differentiation and malignant transformation of B cells.