Dr. Natalie Koehler

The work of our group is focused on tumor immunology and T cell based immunotherapies.

With the advent of allogeneic hematopoietic cell transplantation (allo-HCT) it became possible for the first time to cure patients with high risk leukemias and lymphomas. The reason for this treatment success is the beneficial graft-versus-leukemia (GvL) effect, in which allogeneic T cells present in the graft recognize and eliminate residual leukemia cells. However, the allogeneic T cells can also attack healthy tissues of the recipient, resulting in graft-versus-host disease (GvHD), a severe and potentially life threatening complication of allo-HCT. Therefore our lab is interested in further analysing the molecular mechanisms of these two effects, in order to find potentially new therapies that target GvHD while sparing the beneficial GVL Effect. For this aim we use classical genetic mouse models and T cell characterization approaches as well as novel NGS-based technologies, including single cell RNA sequencing.

The second focus of our research is the identification of novel targets for immunotherapies in hematological malignancies, in particular key regulators of immune checkpoint molecules. With the development of immune checkpoint inhibitors (ICI), the treatment landscape of numerous cancer entities has been revolutionized. A substantial fraction of patients respond to ICI and responses are frequently durable and even curative. However, by increasing the patient��s endogenous immune response, ICI can also induce severe immune-related adverse events (irAEs), which oftentimes require ICI discontinuation and corticosteroid treatment, hence limiting the success of ICI therapy. So far, there are no reliable biomarkers to identify patients that are at high risk of developing irAEs. Therefore, we aim to elucidate the mechanisms of and find novel biomarkers for irAE development, with a focus on microRNAs.