“Translational studies in myeloid blood cancers and innate immune tolerance”
Solid cancers recruit host immune cells, like macrophages, to facilitate growth yet are able to evade immune recognition. We identified SHIP as a master regulator of the switch between anti-tumour/"killer" (M1) and pro-tumour/"healer" (M2) macrophages. Striking parallels between the SHIP-knockout mouse phenotype and humans with blood cancers (myelodysplastic syndromes - MDS), prompted our discovery of M2-skewing in MDS. We aim to elucidate molecular mechanisms of cancer-macrophage cross-talk and, in parallel, to harness the immunosuppressive potential of M2-macrophages to mediate Factor-VIII tolerance (seen as "foreign") in Hemophilia patients. Approaches include high-throughput translational human pathology, mouse models, genomic and proteomic platforms.
SHIP represses the generation of alternatively activated macrophages.
Rauh MJ, Ho V, Pereira C, Sham A, Sly LM, Lam V, Huxham L, Minchinton AI, Mui A, Krystal G. Immunity. 2005 Oct;23(4):361-74. PMID: 16226502