RTICC International Guest Seminar- Assoc. Prof. Liron Bar-Peled

Assoc. Prof. Liron Bar-Peled
Krantz Family Center for Cancer Research
MGH Cancer Center, Harvard Medical School, USA

“Identification of Druggable and Redox Vulnerabilities in Cancer"

Reactive oxygen species (ROS) are required for normal cellular function, but at high concentrations can lead to human pathologies including cancer and neurodegeneration. While the electron transport chain within the mitochondria is widely appreciated as one of the main physiological generators of ROS within cells, the pathways which sense ROS and regulate its production remain poorly understood.

Using comprehensive base-editing screens, we identify VPS35 as a cytosolic ROS sensor, which regulates mitochondrial translation to control intracellular ROS levels. Mechanistically, we find that oxidation of VPS35 disrupts its function within the Retromer protein trafficking complex, leading to mislocalization of the arginine transporter SLC7A1 and a subsequent decrease in mitochondrial translation. Mitochondrial ROS synergizes with the activity of some chemotherapies to induce tumor killing, and we identify that oxidation or depletion of VPS35 leads to cisplatin resistance in ovarian cancer models.

Collectively, these findings demonstrate a mechanism by which cytosolic ROS sensing impinges on mitochondrial function to control ROS levels.

The RTICC aspires to become a leading center, attracting top-tier researchers renowned both nationally and internationally for their contributions to cancer research in various fields.
A key objective is to foster collaborations and engage with leading scientists, all with the aim of advancing cancer treatment and improving patient outcomes. Therefore, we host the RTICC International Guest Seminar, which is delivered by acclaimed expert academic speakers.