Clonal haematopoiesis of indeterminate potential (CHIP), is an aging-related condition in which a significant proportion of one’s blood is produced from a single stem cell clone carrying a leukaemia-associated mutation. CHIP is associated with an increased risk of lung cancer and other myeloid-inflammation driven pathologies. CHIP myeloid cells, and especially those with TET2 mutations, are hyperresponsive and hyperinflammatory—properties that could promote tumour initiation if an activated, CHIP myeloid cell is within the vicinity of an oncogene-expressing epithelial cell. Yet, we lack an understanding of how CHIP myeloid cells infiltrate, accumulate, and function within normal tissues and whether they indeed promote tumour initiation. In this project, Dr. Pospori will investigate the dynamic changes in the recruitment and accumulation of Tet2mut myeloid cells into the lung, following exposure to air pollution—an inflammatory insult known to promote tumour initiation. Dr. Pospori will ask whether CHIP and tissue-CHIP synergise or depend on air-pollution exposure to promote tumour initiation. This work will inform our understanding of how CHIP myeloid cells interact with oncogene-expressing epithelial cells during tumour initiation and with malignant cells, as regions of hyperplasia eventually progress to become lung adenocarcinomas.
Dr. Constandina Pospori joined Professor Charles Swanton’s lab at the Francis Crick Institute as a senior postdoc to investigate the impact of clonal haematopoiesis on lung cancer initiation and progression. Her previous research focused on leukaemic stem cell responses to IFNγ-driven inflammation. She is an MB PhD graduate from University College London Medical School.