HEИндивидуална стипендия2023–2025

PreCODE · Identifying the role of injury-associated cellular reprogramming in the early oncogenic transformation of human colonic epithelium

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-09-01 → 2025-08-31
Финансиране от ЕС: 214 934 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Клетъчните промени при възпаление на дебелото черво се анализират, за да се разбере как нараняванията помагат на мутациите да превърнат здравите клетки в ракови. Това помага за откриване на нови начини за ранно засичане на рака при групи с висок риск.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Identifying the role of injury-associated cellular reprogramming in the early oncogenic transformation of human colonic epithelium

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, making it a critical public health and healthcare challenge. Patients with ulcerative colitis (UC), a chronic inflammatory disease of the colon, are at particularly high risk of developing colitis-associated CRC. Despite this well-established link, the precise mechanisms by which epithelial injury and inflammation contribute to tumor initiation remain unclear, limiting opportunities for effective prevention and early intervention. This project addresses this gap by investigating how injury alters the vulnerability of colonic epithelial cells to oncogenic transformation, using advanced human organoid and CRISPR-based models. By uncovering how early mutations interact with injury states to shift epithelial recovery trajectories, the project aims to identify novel windows for early CRC detection and intervention. In the broader political and strategic context of rising cancer incidence and the urgent need for preventive oncology, these insights could inform new approaches to monitoring high-risk patient populations and ultimately reduce the global burden of CRC.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Colorectal cancer represents a major public health problem being the second leading cause of cancer-related deaths worldwide. The treatment management of the already developed disease is however often time-consuming, expensive and rarely 100% effective. Therefore, the goal should be to start diagnosing and managing the diseased state as early as possible when cancer is still curable. The early cellular transformation events remain poorly understood as cancer-associated mutations have been found to be surprisingly prevalent in seemingly healthy tissues, suggesting the requirement for a potent trigger mechanism. With this project, I aim to study the early colonic transformation via a completely unique hypothesis and approach. My strategy is built on the emerging new “injury-triggered fetal-like state” concept guided by my host lab and the hypothesis that oncogenic mutations require transcriptional reprogramming to a more susceptible fetal-like state to trigger transformation. This hypothesis relies on the fact that the fetal-like state is observed during injury and also in subsets of tumors indicating that cellular reprogramming could play a prominent role in promoting oncogenic transformation. As a primary model system, I will make use of my extensive experience with cancer modeling via 3D human-derived organoids and CRISPR technology, and elevate these techniques by the state-of-the-art expertise available at the host lab and/or institution, such as in vivo orthotopic cell transplantation, epigenetic profiling, advanced CRISPR-screening methodology and clinical collaboration. By bringing together such intelligent methodology, I will be able to effectively investigate the role of injury-induced cellular reprogramming in the transformation of human colonic epithelium. The results of this work will shape the future directions of my own prospective lab, but also cancer research in general, promising major new implications on early cancer detection strategies.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания