Researcher Database
Prof. Dr. Heiko Hermeking
Pathologisches Institut
Thalkirchner Str. 36
80337 München
Program
Exploitation of Oncogenic Mechanisms (EOM)
Summary
We are mainly interested in the function of two transcription factors, which are altered in more than 50% of all human tumors: c-MYC and p53. In line with their opposing functions, they are encoded by a proto-oncogene (c-MYC) and a tumor suppressor gene (p53). The majority of colorectal cancer show activation of c-MYC by mutation in the b-catenin/APC pathway and mutational inactivation of p53. In the past, we identified important functional connections between these factors, such as the mediation of c-MYC-induced apoptosis by p53. In addition, we identified and characterized critical effectors of p53 and c-MYC, such as 14-3-3sigma, the miR-34 family of microRNAs (p53) and the BR-HLH-LZ TF AP4 and ZNF281 (c-MYC). Currently, we are studying the biology of these genes in mouse models of colorectal cancer. A focus of the lab is the regulation of metastatic progression as we could show that these factor are involved in the regulation of EMT (epithelial-mesenchymal transition) and its reversal, MET. In addition, we are studying the role of the networks mentioned above in the tumor microenvironment and tumor stem cell biology.
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.