Groundbreaking discovery: MAEA’s unexpected role in DNA repair
A University of Alberta research team has identified a surprising new function for MAEA (macrophage erythroblast attacher), a protein once thought to be primarily involved in red blood cell development. The scientists report in Science Advances that MAEA also plays a critical role in DNA repair and cell replication. When MAEA is removed or inhibited, cancer cells become more vulnerable to chemotherapy, offering a potential path to counteract drug resistance and improve patient outcomes.
How MAEA affects chemotherapy response
The team conducted a broad screen of almost 900 genes to determine which might help cells defend against common chemotherapy drugs used for colorectal, small-cell lung, and ovarian cancers. Their work pinpointed MAEA as a key player in the cell’s repair mechanisms. By disrupting MAEA, cancer cells lose some capacity to fix DNA damage caused by chemotherapy, making treatments more effective in these models.
From developmental disorders to cancer therapy
MAEA was previously linked to neurodevelopmental delays and facial abnormalities due to its role in red blood cell formation. This new evidence shows that mutations affecting MAEA can influence cellular responses to DNA damage, which carries important implications for both pediatric development and cancer therapy. First author Elham Zeinali, a PhD student, notes that the findings deepen our understanding of how MAEA mutations may impact children during development and also point toward practical clinical applications for adults with cancer.
Using AI and collaboration to map the pathway
To understand how MAEA’s newly discovered function interacts with other cellular processes, the researchers partnered with biochemist Mark Glover to apply AlphaFold modelling. This AI-based tool helped model how various MAEA mutations found in kids with developmental disabilities might affect MAEA’s role in repair and replication. Additional collaboration with Université Laval allowed the team to identify compensatory pathways that cancer cells engage when MAEA is not functioning properly. The goal is to design combination therapies that block both MAEA-dependent repair and its backup pathways, potentially preventing resistance from taking hold.
Translational steps toward patient care
Encouragingly, the U of A team is already moving toward clinical relevance. They are collaborating with an American cancer group to test the approach on tissue samples from patients who have relapsed after standard chemotherapy, representing a critical population with limited options. The research is also expanding to other classes of chemotherapy drugs to assess the breadth of MAEA’s impact on treatment responses.
Independent replication underscores credibility
Independent researchers at the University of Cambridge have reproduced the U of A findings, strengthening confidence in MAEA as a potential biomarker and therapeutic target. While developing drugs to target MAEA directly may take years, the team sees near-term potential for MAEA to serve as a biomarker—helping to identify which patients are most likely to benefit from certain chemotherapies and enabling more personalized treatment planning.
What this means for patients and future research
The prospect of reversing drug resistance by targeting MAEA could change how clinicians approach treatment for colorectal, small-cell lung, and ovarian cancers. In addition, understanding MAEA’s role in DNA repair may lead to broader insights into developmental disorders and their interactions with cancer therapies. Future studies will explore the safety and efficacy of MAEA-focused strategies in combination regimens and probe whether MAEA levels in tumors can predict chemotherapy response in routine clinical practice.
About the researchers
The University of Alberta team, led by associate professor Ismail Ismail in the Department of Oncology, continues to push the boundaries between basic genetics and translational cancer care. The collaborative effort highlights how cross-disciplinary work—spanning genetics, biochemistry, AI modelling, and clinical partnerships—can accelerate the path from bench to bedside.
