Forscherdatenbank
Dr. Eric Metzger
Center for Clinical Research
Breisacherstrasse 66
79106 Freiburg i. Br.
Programm
Exploitation of Oncogenic Mechanisms (EOM)
Übersicht
We identified the novel lysine methyltransferase KMT9 writing the chromatin mark histone H4 monomethylated at lysine 12 (H4K12me1). Depletion or enzymatic inactivation of KMT9 blocks not only proliferation of castration and enzalutamide-resistant prostate cancer cells and 3D organoids in vitro but also in xenograft and genetically engineered prostate tumours in vivo. Of note, KMT9 loss does not impair growth of non-transformed cells. The molecular mode of KMT9 action is independent of androgen receptor (AR) function thus, providing a promising, novel therapeutic paradigm for the treatment of castration-resistant prostate cancer (CRPC) exceeding the current gold standard of care. We developed high-potency drug-like KMT9 lead inhibitors displaying unprecedented specificity for KMT9.Here, we aim to develop our lead inhibitors to clinical candidates for phase I clinical testing.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.