Our Research
We have several research areas:
- Translational pediatric cancer research (PI: Nikolas Herold)
- Histiocytosis (PI: Jan-Inge Henter, see separate tab)
The main goal of our translational approach is to find rationale ways to improve survival in childhood cancer. Our strategy to do so is, first, deciphering the cellular and molecular mechanisms that govern resistance to chemo- and immunotherapy. Second, we develop drugs to target newly found resistance factor. Third, we implement clinical trials to close the translational circle. Childhood cancers that we work with include acute myeloid leukaemia, osteosarcoma and Ewing sarcoma.
Herold laboratory has identified the protein SAMHD1 as a major resistance factor to cytarabine (ara-C) and several other nucleoside analogues, a class of antimetabolites used in the treatment of haematological and solid malignancies. Through a phenotypic screen, we identified the compound hydroxyurea to inhibit the ara-CTPase activity of SAMHD1. A phase 1/2 clinical trial has recently concluded patient inclusion and analysis is pending.
As SAMHD1 has a multifaceted role including tumour suppressor functions coupled to reduction of replication-stress-induced inflammation, we aim to further understand the role of SAMHD1 in different cancers to identify tools to fine-tune its function.
More recently, we try to identify factors that regulate drug-drug interaction of combination therapies including immunotherapy: Here, we focus on osteosarcoma, a disease for which survival has stagnated for four decades.
