Dinis Calado

Immunity & Cancer Laboratory

Our immune system is remarkable. It is composed by a network of cells, including T and B cells that work together to protect our body from infection by pathogens such as bacteria, viruses and parasites.

During an immune response to infection, B cells undergo a T cell dependent stage of development, called germinal centre (GC), essential to produce high affinity antibodies against the pathogen. However, to produce such antibodies, B cells in the GC microenvironment undergo processes of DNA mutation and recombination while rapidly dividing, and infidelity in these processes may lead to oncogenic DNA lesions. Indeed the most common types of haematological malignancies in adults, such as Hodgkin and non-Hodgkin lymphomas and multiple myeloma, originate from B cells at the GC stage or from B cells that have passed through the GC. This emphasises the importance of the maturation events within the GC microenvironment for B cell cancer development.

Using an integrative approach to immunology and cancer biology, our Laboratory aims to understand the mechanisms by which healthy GC B cells become cancerous.

We use cutting-edge genetic techniques in vivo in the mouse, including conditional gain-of-function and/or loss-of-function specifically in GC B cells using primarily the Cre-LoxP system. The confirmation and/or validation of the findings in these systems are obtained through the study of human samples of GC B cell derived cancers.

B cell development and cancer

B cell development and cancer

DNA recombination and mutational processes: VDJ rearrangements (VDJ); somatic hypermutation (SHM); class-witch recombination (CSR).

Selected publications

Calado DP, Sasaki Y, Godinho SA, Pellerin A, Köchert K, Sleckman BP, de Alborán IM, Janz M, Rodig S, Rajewsky KThe cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers.
Nat Immunol. 2012 Sep 23. doi: 10.1038/ni.2418. [Epub ahead of print] *Correspondence 

Sander S, Calado DP, Srinivasan L, Köchert K, Zhang B, Rosolowski M, Rodig S, Holzmann K, Siebert R, Bullinger L, Rajewsky K. Synergy between PI3K signalling and MYC in Burkitt lymphomagenesisCancer Cell. 2012;22(2):167-79. 

Calado DP, Zhang B, Srinivasan L, Sasaki Y, Seagal J, Unitt C, Rodig S, Kutok J, Tarakhovsky A, Schmidt-Supprian M, Rajewsky K. Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphomaCancer Cell. 2010;18(6):580-9. *Equal contribution. 

Lu LF, Thai TH, Calado DP*, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, Rudensky AY. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 proteinImmunity. 2009;30(1):80-91. *Equal contribution. 

Srinivasan L, Sasaki Y, Calado DP, Zhang B, Paik JH, DePinho R, Kutok JL, Kearney JF, Otipoby KL, Rajewsky K.
PI3Kinase signaling is responsible for BCRmediated mature B cell survival.
Cell.2009 Oct 30;139(3):57386. 

Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela, D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K. Regulation of the germinal centre response by microRNA-155Science. 2007;316(5824):604-8 

Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, Rajewsky N, Bender TP, Rajewsky K. MiR-150 controls B cell differentiation by targeting the transcription factor c-MybCell. 2007;131(1):146-59. *Equal contribution. 

 

Dinis Calado

Dinis Calado

dinis.calado@crick.ac.uk
+44 (0)20 379 61205

  • Qualifications and history
  • 2006 PhD in Molecular Immunology, University of Lisbon, Portugal
  • 2006 Postdoctoral Fellow, Harvard Medical School, USA
  • 2010 Special Fellow of the Leukemia Lymphoma Society. Harvard Medical School, USA
  • 2013 Establish lab at the London Research Institute, Cancer Research UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK