STAT5 is hyperactivated in a variety of haematopoietic tumours, prominently in Peripheral T-Cell Leukaemia and Lymphoma (PTCL). Hyperactivation of STAT5 is caused either by overexpression of STAT5A or by a somatic gain-of-function mutation in STAT5B (STAT5BN642H), most frequently found in PTCL. Given the proposed interplay of STAT5 with epigenetic modulators, we hypothesize that high levels of activated STAT5 (=pSTAT5Y694, pYSTAT5) form a disease-propagating epigenetic landscape. To study the influence of STAT5 on these oncogenic rearrangements, we have created two transgenic mouse models expressing high levels of pYSTAT5, cSTAT5AFlagHIGH, and STAT5BN642H mice, and two control lines expressing physiological levels of STAT5A or STAT5B. The cSTAT5AFlagHIGH and STAT5BN642H mice develop a PTCL-like disease. Our major goal is to understand the dose effects of STAT5 that lead to potential TF cooperativity and changes in chromatin accessibility. Within the project part, we aim to compare STAT5-dependent epigenomes and interactomes to gain insights into pYSTAT5-dependent chromatin structures that are specific for disease. We will analyze how STAT5 influences the chromatin landscape, (ii) to unravel how this influence is changed during malignant T-cell transformation and (iii) to identify critical cooperativity partners of STAT5 in neoplastic T cells to open novel therapeutic avenues. Heidi is interested in how mutated STAT5 alters the chromatin landscape of different T-cell subsets, driving oncogenic transformation and progression in specific T-cell lymphoma entities. To this end, she is studying disease mechanisms of oncogenic STAT5, highlighting common and unique downstream effectors in specific disease subtypes, which may assist with identifying new targeted therapies for T-cell lymphoma patients.