Philipp J. Rauch, M.D.
2022 Funding recipient
Ontogenetic and functional basis of inflammation in Tet2-mutated clonal hematopoiesis
EvansMDS Young Investigator Award
Clonal hematopoiesis of indeterminate potential (CHIP) describes a recently recognized condition in which
mutations (changes in the DNA) that are typically associated with blood cancers are found in a high proportion of blood cells of an otherwise healthy individual. CHIP is a major risk factor for the subsequent development of blood cancers such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). In addition, CHIP has been found to cause increased inflammation in immune cells, which in turn also increases the risk for non- cancerous conditions such as heart attacks or strokes in affected individuals. Despite years of research, we do not currently understand how blood cells with CHIP mutations grow faster, and why they are more inflammatory than normal blood cells. In this study, I will use 2 state-of-the-art techniques to illuminate these questions: (1) I will use a technique called barcoding which enables tracking of every blood cell in an organism. This will help us understand how the behavior of cells carrying a mutation differs from non-mutated cells. (2) Using CRISPR technology (often described as “genetic scissors”), I will conduct a screen that probes every gene in the genome in an effort to find suitable therapeutic targets that could be used to dampen hyperinflammation in CHIP, while sparing functions of the immune system that are essential to defend against pathogens.