Non-Coding Cancer Biology
Dr. Johannes C. Hellmuth
The Non-Coding Genome plays a fundamental role in human disease including cancer. Our goal is to gain a deeper understanding of the cancer genome’s regulatory circuitry to identify specific vulnerabilities within the non-coding genome of cancer cells.
Our current work focuses on super-enhancers – large regulatory elements in the non-coding genome that act as essential determinants of cell-identity and are closely associated with oncogenic functions in cancer. These super-enhancers differ from regular enhancers in several ways that make them attractive therapeutic targets: they control cell-identity-defining genes, they are highly cell-type specific and they rely on transcriptional condensates, rendering them vulnerable to perturbation.
We aim to leverage the vulnerabilities associated with oncogenic super-enhancers to develop novel diagnostic and therapeutic approaches. Our overarching goal is to advance a fundamentally new strategy in cancer therapy: by targeting individual cell‑type‑defining super‑enhancers, we take aim at the very core of a cancer cell’s identity.
Future projects and goals
- Functional interrogation the non-coding genome
While the full complement of essential coding genes has been mapped in detail, no comparable effort exists for the non-coding genome. We use large‑scale CRISPRi screens to identify essential elements in the non-coding genome of cancer cells and reveal specific vulnerabilities.
- Super-enhancer proteomes
While the general factors universally associated with super-enhancers are known, our knowledge on cell-type-specific transcription factors and cofactors driving individual super-enhancers is incomplete. We use different screening approaches and mass-spectrometry-based assays to systematically analyze proteomes at individual oncogenic super-enhancers.
- Super-enhancers diagnostics
Super‑enhancers are key determinants of cell identity and offer a unique window into the oncogenic regulatory networks of tumor cells, providing a functionally informative layer of the epigenome. Integrating these data with existing omics datasets will enhance our understanding of tumor biology and enable more precise, personalized therapeutic strategies. We therefore plan to develop assays to monitor super‑enhancer activity non‑invasively and in tumor samples.
Dr. Johannes Hellmuth
DKTK Junior Klinische Kooperationseinheit Non-Coding Cancer Biology
LMU Klinikum, Pathologisches Institut der LMU