The Tomida Lab investigates the molecular decision-making processes within DNA repair pathways, focusing on how cells coordinate DNA damage signaling to maintain genomic integrity. Our active research focuses on the following topics:
Regulation of the ATR-ATRIP Signaling Axis
We study mechanisms that govern ATR kinase, the master regulator of the replication stress response. Our recent work (Nucleic Acids Research, 2026) demonstrated that the DNA repair protein REV7 binds to ATRIP to inhibit ATR kinase activity, providing a novel layer of ATR regulation.
We are investigating how this inhibitory mechanism is mediated – the factors and cellular events that influence the association/dissociation of REV7 and ATRIP, and how we might modulate the REV7-ATRIP interface for therapeutic benefit when ATR activity is dysregulated, as in Seckel syndrome or malignancy.
Coordination of p53 and Checkpoint Signaling
We recently characterized a REV7-p53 interaction (Cell Cycle, 2024) that inhibits ATM-mediated DNA damage signaling, identifying a key gatekeeper of the DNA damage response. Our ongoing research focuses on mapping the structural domains of this interaction to understand how REV7 regulates p53 activity and p53 protein destabilization. Given that p53 is a key tumor suppressor and “guardian of the genome,” defining the mechanistic interactions between REV7 and p53 has the potential to elucidate mechanisms of pathogenic gain-of-function in p53.
DNA Repair Drivers of Prostate Cancer Metastasis
Beyond genomic instability, we investigate how alterations in DNA repair pathways promote metastasis in prostate cancer. Our lab has identified DNA repair-associated factors that are downregulated during the transition to metastatic disease. We aim to identify novel biomarkers for early metastatic detection and druggable targets to prevent cancer progression.