Researcher Database
Prof. Dr. Thomas Kindler
Universitätsmedizin Mainz
Langenbeckstr. 1
55131 Mainz
Program
Exploitation of Oncogenic Mechanisms (EOM)
Summary
Malignant transformation is a multifaceted process characterized by the acquisition of somatic mutations and modulation of the epigenetic landscape. In concert, these alterations result in rewired signaling pathways and the activation of aberrant transcriptional programs followed by uncontrolled proliferation, impaired differentiation and invasive cell growth. A detailed understanding of cancerogenesis represents a prerequisite to identify drug targets, tumor-specific vulnerabilities and novel therapeutic approaches in personalized oncology.
Specific interests of our group include: i) oncogene-mediated dysregulation of DNA damage repair. In particular, we aim to explore the role of oncogenic KRAS on replicative stress, regulation of DNA repair pathway choice and synthetic dependencies, e.g. on PARP inhibition; ii) STAT5-dependent modulation of transcriptional networks and epigenetic programs in cancer cells with a strong focus on the analysis of distinct posttranslational modifications; and iii) patient-oriented research to understand and improve personalized treatment strategies in precision oncology. To address these questions, we take advantage of well-established experimental approaches, computational analyses and tumor models including genetically engineered mouse models or primary patient samples.
More information you will find at the UCT Mainz Website and at the Kindler Lab.
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.