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, 2021, Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma, Nature Communications, Vol:12, ISSN:2041-1723, Pages:1-16
et al., 2021, Systems level profiling of chemotherapy-induced stress resolution in cancer cells reveals druggable trade-offs, Proceedings of the National Academy of Sciences of Usa, Vol:118, ISSN:0027-8424
et al., 2021, The innate sensor ZBP1-IRF3 axis regulates cell proliferation in multiple myeloma., Haematologica
et al., 2021, Brd2/4 and Myc regulate alternative cell lineage programmes during early osteoclast differentiation in vitro, Iscience, Vol:24, ISSN:2589-0042, Pages:1-31
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