Skip to main content
The William Harvey Research Institute - Faculty of Medicine and Dentistry

Breadcrumb

  1. WHRI
  2. Study
  3. Barts Charity Doctoral Training Programme
  4. Projects
  5. BC-DTP_2026_18

Targeting DNA damage repair pathways in YAP/TAZ-driven squamous cell carcinoma as a novel therapeutic strategy

Code: BC-DTP_2026_18

Title: Targeting DNA damage repair pathways in YAP/TAZ-driven squamous cell carcinoma as a novel therapeutic strategy.

Primary Supervisor: Gernot Walko

Email: g.walko@qmul.ac.uk

Institute: Institute of Dentistry

Secondary Supervisor: Adrian Biddle

Email: a.biddle@qmul.ac.uk

Institute: Blizard Institute

Lay Summary:

Squamous cell carcinoma (SCC) is one of the most common cancers worldwide. It can develop in the skin (cutaneous SCC) or in the head and neck region. While skin SCC rarely spreads, it can be life-threatening for people with weakened immune systems, such as organ transplant patients. Head and neck SCC is less frequent but far more aggressive, often linked to smoking, heavy alcohol use, and certain viral infections. Unfortunately, treatment options for advanced SCC—especially those not caused by human papillomavirus—remain very limited, and survival rates are poor.

Our research focuses on two key processes that help SCC cells survive and resist treatment. First, the proteins YAP and TAZ act as “master switches,” driving cancer growth and therapy resistance. Second, SCC cells rely on DNA damage repair pathways to fix genetic damage and cope with stress during cell division. We have discovered that SCC cells with highly active YAP/TAZ experience severe stress when copying their DNA, but they survive by boosting DNA repair systems. This creates a weakness: if we block these repair pathways, the cancer cells may die.

This project will investigate how YAP/TAZ interact with DNA repair pathways and test whether targeting these systems together can kill SCC cells more effectively. Our ultimate goal is to develop new treatments that improve survival and reduce side effects, particularly for patients in East London, where head and neck cancers are more common and health inequalities lead to worse outcomes.

Aims:

Aim 1: Define the molecular mechanisms by which YAP/TAZ hyperactivation induces replication stress in cSCC and HNSCC cells.

Aim 2: Identify key mediators downstream of YAP that contribute to its role in DNA damage repair.

Aim 3: Evaluate therapeutic strategies targeting replication stress and DNA damage repair in YAP/TAZ-hyperactive SCC models.

Aim 4: Assess biomarkers predictive of response to replication stress-targeted therapies in patient-derived samples from East London cohorts

Back to top