My laboratory focuses on 3 areas of research:
1) Molecular and cellular pathogenesis of mutliple myeloma and other mature B cell malignancies.
Our specific areas of interest include the delineation and characterisation of myeloma propagating cells, the role of transcription factor deregulation in the pathogenesis of mutliple myeloma and understanding of the mechanisms of osteoclast activation and bone disease in myeloma.
2) The biology of glycolipid specific T cells, their role in haematological disease and their therapeutical potential.
We are particularly interested a) in the role of invariant NKT cells in allogeneic stem cell transplantation and their therapeutic potential for CD1d-expressing B cell malignancies and b) in the role of gycosylphosphatidylinositol-specific T cells in the pathogenesis of paroxysmal nocturnal haemoglobinuria.
3) Understanding the transcriptional and epigenetic basis of housekeeping gene regulation and its therapeutic implications for autosomal recessive mendelian disease.
We adress these aims by using inherited GPI deficiency and disorders of the glycolytic pathway as disease models.
There is substantial conceptual and practical overlap between these 3 areas of research.
We employ a variety of molecular and cell biology tools, including genomics, advanced flow-cytometry and animal models.
We increasingly integrate and interprete our research through systems biology approaches through a close collaboration with Prof Michael Stumpf and his group, Theoretical Systems Biology, Imperial College.
As part of my clinical activities I participate and lead locally phase III clinical trials. In conjunction with the pharmaceutical industry we are working towards developing our capacity for early phase I/II clinical trials for lymphoma and myeloma.
Karadimitris A, 2020, Cord Blood CAR-NK Cells: Favorable Initial Efficacy and Toxicity but Durability of Clinical Responses Not Yet Clear, Cancer Cell, Vol:37, ISSN:1535-6108, Pages:426-427
et al., 2018, Enhanced anti-lymphoma activity of CAR19-iNKT cells underpinned by dual CD19 and CD1d targeting, Cancer Cell, Vol:34, ISSN:1535-6108, Pages:596-610
Rotolo A, Karadimitris A, Ruella M, 2018, Building upon the success of CART19: chimeric antigen receptor T cells for hematologic malignancies, Leukemia & Lymphoma, Vol:59, ISSN:1042-8194, Pages:2040-2055
et al., 2017, High resolution IgH repertoire analysis reveals fetal liver as the likely origin of life-long, innate B lymphopoiesis in humans, Clinical Immunology, Vol:183, ISSN:1521-6616, Pages:8-16
et al., 2016, Overexpression of RANKL by invariant NKT cells enriched in the bone marrow of patients with multiple myeloma, Blood Cancer Journal, Vol:6, ISSN:2044-5385