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Bone Marrow Failure & MDS

Immunology

Team Lead

Dr Sharam Kordasti
Lecturer
E-mail: sharam.1.kordasti@kcl.ac.uk

Tel: +44(0)207 848 5920

Dr Kordasti - Biography

Following graduation from medical school and clinical training in Internal Medicine/ Haematology, Dr Kordasti received his MSc in Medical Immunology and PhD in Cancer studies from King’s College London. His PhD project was on the role of regulatory T cells (Tregs) in Myelodysplstic syndrome (MDS). He established the role of Tregs in MDS and their effects on disease progression and response to treatment. He continued his work at King’s College London as a senior clinical research fellow and also developed an interest in the immunobiology of aplastic anaemia (AA) during this time. He has been appointed as a lecturer in the department of Haematological Medicine at King’s College London since January 2012 and continues to study the immunobiology of bone marrow failure syndromes, in particular AA and MDS.

His main research interest is the plasticity of CD4+ T cells and their role in the immunobiology of bone marrow failure syndromes in particular AA and MDS.

He also supervises PhD students and post-doctoral fellows for their research projects.

Research Focus

The main focus of the Immunology unit is the role of immune system in the development of Bone Marrow Failure (BMF) syndromes and the interaction between the immune system and malignant clones. We have shown the importance of CD4+ T cells namely Tregs and Th17 components in the pathogenesis of MDS and AA as well as the transformation of an inflammatory environment of low risk disease to a more suppressive/ dysfunctional immune response in high risk disease.The research program is composed of two integrated themes:

  • The mechanisms of ineffective immune-response and immune escape in high risk Myelodysplastic Syndrome (MDS) which leads to disease transformation to acute Leukaemia and the study of autoimmune response in low risk MDS / Aplastic Anaemia (AA).
  • The role of persistent inflammation in acquiring genetic mutations and subsequent disease progression.

We use Flowcytometry (both conventional and mass cytometry (CyTOF)) as the primary methods to identify specific immune signatures for the prediction of disease progression and response to immunosuppressive and immunomodulatory treatments. We are also investigating the off target effects of non-immunomodulatory medication on immune system in BMF. Integrated with molecular tools that target immune signaling pathways, we are looking  for potential therapeutic applications.

We are also working on different cell therapy strategies (i.e. in vitro expansion of Tregs) to reintroduce a balance immune response in low risk MDS and AA and prevent proliferation pressure and reduce the risk of acquired genetic mutation and disease progression while maintaining an effective immune surveillance against malignant clones

The Immunology Unit Team

Researchers:

Dr Frederic Toulza

Ms Pilar Perez Abellan

Current students:

Dr Nathalie Kerkhoff (PhD student)

Ms Cinzia Benfatto (PhD Student)
Former students:
Dr Clodagh Keohane (MD student)
Dr Marijn Kramer (Research Fellow)
Dr Benedetta Costantini (Research Fellow)
Dr Caroline Veen (Research Fellow)
Dr Astrid Olsnes Kittang (Research Fellow)

Dr Sufyan Al-Khan (Research Fellow)

 

Selected Publications

  1. The effects of 5-azacytidine on the function and number of regulatory T cells and T-effectors in myelodysplastic syndrome. Costantini B, Kordasti SY, Kulasekararaj AG, Jiang J, Seidl T, Abellan PP, Mohamedali A, Thomas NS, Farzaneh F, Mufti GJ. Haematologica. 2013 Aug;98(8):1196-205. doi: 10.3324/haematol.2012.074823. Epub 2012 Dec 14.
  2. Rationale for the clinical application of flow cytometry in patients with myelodysplastic syndromes: position paper of an International Consortium and the European LeukemiaNet Working Group. van de Loosdrecht AA, Ireland R, Kern W, Della Porta MG, Alhan C, Balleisen JS, Bettelheim P, Bowen DT, Burbury K, Eidenschink L, Cazzola M, Chu SS, Cullen M, Cutler JA, Dräger AM, Feuillard J, Fenaux P, Font P, Germing U, Haase D, Hellström-Lindberg E, Johansson U, Kordasti S, Loken MR, Malcovati L, te Marvelde JG, Matarraz S, Milne T, Moshaver B, Mufti GJ, Nikolova V, Ogata K, Oelschlaegel U, Orfao A, Ossenkoppele GJ, Porwit A, Platzbecker U, Preijers F, Psarra K, Richards SJ, Subirá D, Seymour JF, Tindell V, Vallespi T, Valent P, van der Velden VH, Wells DA, de Witte TM, Zettl F, Béné MC, Westers TM. Leuk Lymphoma. 2013 Mar;54(3):472-5. doi: 10.3109/10428194.2012.718341. Epub 2012 Sep 14. Review.
  3. Prospective study of rabbit antithymocyte globulin and cyclosporine for aplastic anemia from the EBMT Severe Aplastic Anaemia Working Party. Marsh JC, Bacigalupo A, Schrezenmeier H, Tichelli A, Risitano AM, Passweg JR, Killick SB, Warren AJ, Foukaneli T, Aljurf M, Al-Zahrani HA, Höchsmann B, Schafhausen P, Roth A, Franzke A, Brummendorf TH, Dufour C, Oneto R, Sedgwick P, Barrois A, Kordasti S, Elebute MO, Mufti GJ, Socie G; European Blood and Marrow Transplant Group Severe Aplastic Anaemia Working Party. Blood. 2012 Jun 7;119(23):5391-6. doi: 10.1182/blood-2012-02-407684. Epub 2012 Apr 27. Erratum in: Blood. 2013 Jun 20;121(25):5104. Höchsmann, Britta [added].
  4. Functional characterization of CD4+ T cells in aplastic anemia. Kordasti S, Marsh J, Al-Khan S, Jiang J, Smith A, Mohamedali A, Abellan PP, Veen C, Costantini B, Kulasekararaj AG, Benson-Quarm N, Seidl T, Mian SA, Farzaneh F, Mufti GJ. Blood. 2012 Mar 1;119(9):2033-43. doi: 10.1182/blood-2011-08-368308. Epub 2011 Dec 2.
  5. Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab. Matthews K, Lim Z, Afzali B, Pearce L, Abdallah A, Kordasti S, Pagliuca A, Lombardi G, Madrigal JA, Mufti GJ, Barber LD. Haematologica. 2009 Jul;94(7):956-66. doi: 10.3324/haematol.2008.003103. Epub 2009 Jun 2.
  6. Human CD80/IL2 lentivirus-transduced acute myeloid leukaemia (AML) cells promote natural killer (NK) cell activation and cytolytic activity: implications for a phase I clinical study. Ingram W, Chan L, Guven H, Darling D, Kordasti S, Hardwick N, Barber L, Mufti GJ, Farzaneh F. Br J Haematol. 2009 Jun;145(6):749-60. doi: 10.1111/j.1365-2141.2009.07684.x. Epub 2009 Apr 20.
  7. Human CD80/IL2 lentivirus transduced acute myeloid leukaemia cells enhance cytolytic activity in vitro in spite of an increase in regulatory CD4+ T cells in a subset of cultures. Ingram W, Kordasti S, Chan L, Barber LD, Tye GJ, Hardwick N, Mufti GJ, Farzaneh F. Cancer Immunol Immunother. 2009 Oct;58(10):1679-90. doi: 10.1007/s00262-009-0679-6. Epub 2009 Mar 13.
  8. IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome. Kordasti SY, Afzali B, Lim Z, Ingram W, Hayden J, Barber L, Matthews K, Chelliah R, Guinn B, Lombardi G, Farzaneh F, Mufti GJ. Br J Haematol. 2009 Apr;145(1):64-72. doi: 10.1111/j.1365-2141.2009.07593.x. Epub 2009 Feb 3.
  9. CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Kordasti SY, Ingram W, Hayden J, Darling D, Barber L, Afzali B, Lombardi G, Wlodarski MW, Maciejewski JP, Farzaneh F, Mufti GJ. Blood. 2007 Aug 1;110(3):847-50. Epub 2007 Apr 5.
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