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Research groups

Regenerative Medicine

Team Leader

Professor Francesco Dazzi
Professor of Regenerative Medicine
Email: francesco.dazzi@kcl.ac.uk
Tel: (44) 020 7848 5888

Research focus

When inflammation meets tissue regeneration
The expertise of Prof Dazzi’s team focuses on the biology and clinical applications of cellular therapies for regenerative medicine. The central goal of regenerative medicine is to replace damaged or diseased tissue. Although traditionally associated with the transplantation of autologous or allogeneic stem cells, the data produced in recent years have led to a paradigm shift in regenerative medicine, according to which endogenous tissue repair can be promoted by controlling host inflammatory pathways. Along these lines, the main interest of the team is to understand the anti-inflammatory properties of mesenchymal stromal cells (MSC) and their interaction with myeloid accessory cells (monocytes and macrophages). Prof Dazzi has already initiated a national clinical programme based on MSC infusions to treat patients with immune mediated disorders, primarily graft-versus-host disease, but more recently autoimmune disease (Crohn’s) and solid organ transplantation.

 

The major players of the group are (in alphabetical order):

  • Dr Luigi Dolcetti (PhD) is looking into the transcriptomics and microRNA regulation of MSC-mediated immunosuppression with the ultimate view of identifying new molecules capable of triggering in situ MSC beneficial activity.
  • Dr Antonio Galleu (MD) aim is to discover the pathways which promote the activation of MSC therapeutic activity in the host. His results will identify not only the key mechanisms of this process, but also biomarkers to select the patients who are more likely to respond to MSC therapies.
  • Dr Cristina Trento (PhD) has discovered a key liaison between MSC and myeloid cells through which a complex network of immune regulation is generated. This loop, which regulates tissue homeostasis, is hijacked by leukaemia to protect malignant progenitors from the host immune attack and chemotherapy.
  • Alice Wang (MRes) and Dr Rehiana Ali (MD) are PhD students with an interest in the MSC activity on metabolism. Dr Ali is also coordinating a study on MSC treatment for multiple sclerosis.

The MSC clinical programme is currently being transferred from Imperial College (Prof Dazzi’s previous site) and taken to a new level with the use of different cell sources and bioengineering approaches. Two key persons are in charge: Dr Stephen Marley (PhD) who has successfully looked after the R&D aspects of MSC clinical programme in the last 3 years. He is equipped with long-standing research experience and with knowledge in biotech R&D. Steve has now been joined by Dr Ling Weng (PhD), the Lab Manager. Ling can exhibit an outstanding research record in transplantation immunobiology and a large experience in immune cell cultures.

Collaborations:

Internal: Prof John McGrath – Dr Dusko Ilic – Dr Emanuele de Rinaldis – Prof Giovanna Lombardi – Prof Fiona Watt


External:
Prof Henning Walczak (UCL) – Prof Maria Belvisi (Imperial) – Prof Jane Apperley (Imperial) – Prof Jacques Galipeau (Emory) – Dr Jeff Karp (Harvard) – Dr Cristina Navarrete (NSHBT) – Prof Vincenzo Bronte (Padua University)

Selected Publications

  1. Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, and Dazzi F. Bone marrow mesenchymal stem cells inhibit the response of naïve and memory antigen-specific T cells to their cognate peptide. Blood 101:3722-9, 2003.
  2. Glennie S, Soeiro I, Dyson JP, Lam E, Dazzi F. Mesenchymal stem cells Mesenchymal stem cells induce division arrest anergy of activated T cell. Blood, 105(7):2821-7, 2005.
  3. Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D, Dazzi F. Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia. 2007 Feb;21(2):304-10.
  4. Weng L, Dyson J, Dazzi F. Low-intensity transplant regimens facilitate recruitment of donor-specific regulatory T cells that promote hematopoietic engraftment. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8415-20.
  5. Tisato V, Naresh K, Girldstone J, Navarrete C, and Dazzi F. Mesenchymal Stem Cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia 2007 Sep;21(9):1992-9.
  6. Jones SP, Horwood NJ, Cope AJ and Dazzi F. Mesenchymal stem cell mediated immunosuppression is not confined to progenitor status. J Immunol 2007, Sep 1;179(5):2824-31
  7. Lymperi S, Horwood N, Marley S, Gordon MY, Cope AP, Dazzi F. Strontium can increase some osteoblasts without increasing haematopoietic stem cells. Blood. 2008 Feb 1;111(3):1173-81.
  8. Vianello F, Villanova F, Tisato V, Lymperi S, Ho KK, Gomes AR, Marin D, Bonnet D, Apperley J, Lam EW, Dazzi F.        Bone marrow mesenchymal stromal cells non selectively protect chronic myeloid leukemia from imatininb-induced apoptosis via the CXCR4/CXCL12 axis. Haematologica. 2010 Jul;95(7):1081-9.
  9. Mussai F, De Santo C, Abu-Dayyeh I, Booth S, Quek L, McEwen-Smith RM, Qureshi A, Dazzi F, Vyas P, Cerundolo V. Acute myeloid leukaemia creates an arginase-dependent immunosuppressive microenvironment. Blood 2013 Aug 1;122(5):749-58.
  10. Vianello F, Cannella L, Golshayan D, Marelli-Berg F, Dazzi F. Enhanced and aberrant T cell trafficking following total body irradiation: a gateway to GVHD?. Br J Haematology 2013 Sep;162(6):808-18.
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