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At CEL, we are dedicated to understanding one of the most fundamental questions in modern biology: how a healthy cell becomes a cancer cell and how we can treat that cancer.
We focus on the epigenome, a complex layer of chemical instructions that sits "above" the DNA. These instructions act like a conductor, telling different genes when to play and when to be silent. This epigenetic control is what makes a brain cell different from a skin cell, even though both have the exact same DNA.
Our central mission is to decode this faulty epigenetic wiring. By understanding how cancer cells hijack this system, we aim to discover new vulnerabilities and develop the next generation of targeted therapies.
Oncohistones, Genomic Instability, and Tumorigenesis
Some of the most aggressive and hard-to-treat cancers are not caused by traditional DNA mutations, but by direct mutations in the histone proteins that package DNA. These "oncohistone" mutations are known to disrupt the entire epigenetic landscape of a cell. They block key repressive marks or activating marks, leading to a massive change in gene expression that can cause a tumor. However, a parallel theory suggests these oncohistones also cause tumors by making the entire genome unstable. We are investigating the "how." Our lab is focused on understanding how the changes in histone modifications (PTMs) caused by these oncohistones directly impact genome stability.
Oncohistones, Genomic Instability, and Tumorigenesis
This illustration describes how these oncohistones alter the bindings of reader, writer, and eraser proteins to promote transcriptional regulation and genomic instability.
Enhancing CAR T-Cell Therapy for "hard-to-treat" Cancers
Enhancing CAR T-Cell Therapy for "hard-to-treat" Cancers
Chimeric Antigen Receptor (CAR) T cell therapy has been a revolutionary success for treating haematological cancers. Our goal is to make this powerful "living drug" work for hard-to-treat cancers, which remain a much greater challenge. We believe that by targeting the epigenetic markers, we can "reprogramme" either the tumour cells or the CAR T cells themselves. This could make the tumour "visible" to the immune system, make the T cells more persistent, and ultimately enhance the anti-tumour potential of CAR T cell therapy against hard-to-treat cancers.
Enhancing CAR T-Cell Therapy for "hard-to-treat" Cancers
Enhancing CAR T-Cell Therapy for "hard-to-treat" Cancers
T cells are engineered to express a CAR and an epigenetic modulator. These modified CAR T cells then bind to and kill target cancer cells. The hypothesis is that this epigenetic modification enhances antitumor efficacy and reduces T cell exhaustion.
Synthetic Lethal Therapies for DNA Damage Repair-Deficient Cancers
Synthetic Lethal Therapies for DNA Damage Repair-Deficient Cancers
Many cancers, including a large subset of colorectal cancers (CRC), have a critical defect in their DNA Damage Repair system. While this defect is what makes them cancerous, it also creates a unique vulnerability. Our lab is exploiting this weakness to find new, highly targeted therapies using a "synthetic lethal" approach.
Synthetic Lethal Therapies for DNA Damage Repair-Deficient Cancers
Synthetic Lethal Therapies for DNA Damage Repair-Deficient Cancers
Our research is structured in a three-phase "screen-to-system" pipeline to discover and validate new drug targets. We screen for "writers" and "erasers" that are essential for the survival of these DNA Damage Repair-deficient cancer cells, but not healthy cells. We then use genomic and molecular assays to understand why these "writers" and "readers" are critical. Finally, we validate our findings using patient-derived organoids and mouse models to develop new, targeted drugs.
Copyrights © Cancer Epigenomics Laboratory, National Institute of Immunology
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