In the recent years the old cell cycle kinase CDK6 came into spotlight of several different cancers. Previously our lab and others identified novel roles for CDK6, going beyond its classical cell cycle function, including its involvement in transcriptional regulation. The focus of the team is to clarify the CDK6 specific network and pathways through the hematopoietic tree and the variety of leukemic subtypes. By using several mouse models, in vitro tools, omics data and bioinformatics we try to unravel the complexity of CDK6 and its interaction partners. These data help us generating novel treatment strategies for precise disease subtypes.
Each member of the CDK6 team works on a different angle which results in a lot of fruitful interaction between the projects and data.

Natural killer (NK) cells are an important component of the innate immunity and provide a first-line of defense against tumors and viral infections. Owing to their ability to engage with tumor targets without the need of specific antigens, NK cells are currently exploited as an attractive tool in cancer immunotherapy against a wide range of cancers such as breast cancer, acute myeloid leukemia, lung cancer and melanoma. NK cells have several additional advantages over T cells in immunotherapy: lower risk for graft-versus-host disease, mediating graft-versus-tumor immunity without attacking normal tissues, usage of allogeneic donor material allows for the generation of off-the-shelf products.

Nonetheless, NK cell hyperactivation or dysfunction is also associated with the pathogenesis of various inflammatory and autoimmune diseases. Also neoplasms of mature NK cells can occur – comprising very rare but highly aggressive diseases with limited available treatment options.

Our research focuses on NK cells from different perspectives. On the one hand, we study NK cell-mediated anti-tumor responses as well as immune evasion/exhaustion mechanisms that affect their functionality, aiming to identify new therapeutic strategies to harness the cytotoxic potential of NK cells. On the other hand, we investigate genetic drivers of and therapeutic options for rare NK cell malignancies and the role of NK cells in autoimmune diseases, such as Multiple Sclerosis.

We contribute to a better understanding of the JAK/STAT signaling pathway in hematopoiesis and leukemia. When part of this pathway is hyperactive – for instance due to mutations in STAT3 or STAT5B – various forms of leukemia can develop. We aim to understand these disease-initiating and –driving mechanisms to identify “points-of-attack” for treatment strategies. To achieve this, we use a wide array of approaches – transgenic murine models, innovative in vitro systems, patient-derived cells and state-of-the-art NGS methods.

We are especially interested in STAT5A and STAT5B – two genes considered to act highly redundant in differentiated blood cells. We revisit and challenge this dogma in hematopoietic stem cells and STAT5-driven leukemia. Another main task is to define the molecular consequences of STAT3 activating mutations that occur in leukemia patients. We highly interact with the other teams of the Sexl Lab – not least due to investigating CDK6/STAT interplays in various hematopoietic malignancies.

Our research topics are the role of mitochondria and mitochondrial ROS as drug targets and in toxicological mechanisms. Recent research activities focused on the one hand on the involvement of mitochondria as drug targets in protozoal and cancer cells. On the other hand our latest research activities have shown that endoperoxides can be useful antileishmanial drugs in vitro and in vivo. A current project is elucidating the mechanism why these endoperoxides are more toxic to protozoal parasites than to mammalian host cells, such as macrophages.

Research into veterinary pharmacology and therapeutics are a major focus within my group. Research activities cover clinical, medical and technological aspects including development of veterinary pharmaceuticals. The main focus is on food producing animals including horses and camelids.