Projects Offered

1 PhD project offered in the IPP summer call Molecular Biomedicine & Ageing

Scientific Background

Myeloproliferative neoplasms (MPNs) are blood cancers that arise from mutated hematopoietic stem cells. Interferon-α (IFN-α) is an approved treatment and works for many patients, but we still do not fully understand how its effects connect to “interferon-stimulated genes” (ISGs) and immune control of the disease.

In related work on acute myeloid leukemia (AML), we identified a chromatin regulatory complex controlled by the enzymes p300 and CREBBP that suppresses ISG expression. Blocking the catalytic activity of p300/CREBBP releases this repression, enables stronger ISG activation, and reduces persistence of malignant stem/progenitor cells. A clinically active p300/CREBBP inhibitor is currently in development and is expected to enter clinical trials in late 2026.

PhD Project: Targeting p300/CREBBP to Enhance Interferon Signaling in Myeloproliferative Neoplasms

This project will test how pharmacological inhibition of p300/CREBBP reshapes ISG programs in MPN and how this affects malignant stem cells and their interaction with the immune system. You will (i) characterize how p300/CREBBP inhibition changes ISG expression and stem cell states in MPN models, (ii) assess consequences for immune effector cells in the MPN context, and (iii) evaluate the therapeutic potential of combining p300/CREBBP inhibition with IFN-α to enhance disease control.

Overall, the goal is to generate mechanistic and translational insight into whether boosting interferon signaling via p300/CREBBP inhibition can be leveraged as a targeted strategy for MPN treatment.

If you are interested in this project, please select Sasca as your group preference in the IPP appcliation platform.

Publications relevant to this project

Shah V, Giotopoulos G, Osaki H, Meyerhöfer M, Meduri E, Gallego- Crespo A, Behrendt MA, Saura-Pañella M, Tarkar A, Schubert B, Yun H, Horton SJ, Agrawal-Singh S Dr, Hähnel PS, Basheer F, Lugo D, Eleftheriadou I, Barbash O, Dhar A, Kühn MWM, Guezguez B, Theobald M, Kindler T, Gallipoli P, Yeh PS, Dawson MA, Prinjha RK, Huntly BJP, Sasca D. (2025) Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation. Blood. Feb 13;145(7):748-764. doi: 10.1182/blood.2022019306 Link

Meyerhöfer M, Zhou Y, Gallego-Crespo A, Shah V, Behrendt MA, Saura-Panella M, Häupl B, Todoriuk O, Hartmann M, Klein M, Wölfel C, Haehnel PS, Michel C, Muth S, Kindler T, Bopp T, Schild H, Horton SJ, Radsak M, Theobald M, Vassiliou GS, Huntly BJP, Kühn MWM, Butter F, Oellerich T, Sasca D. Inhibition of p300/CREBBP catalytic activity drives context-dependent transcriptional activation in AML. Under consideration, Blood.