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Research interests

Secreted and membrane proteins are translocated into the Endoplasmic Reticulum (ER) in an unfolded state. The ER comprises many enzymes and chaperones that ensure productive protein folding. Different physiological and chemical factors that compromise ER homeostasis lead to ER stress. To cope with this situation, cells activate intracellular signaling pathways that are known as the unfolded protein response (UPR), which initially aims at restoring ER homeostasis. Like many other human diseases; some cancer types are associated with ER stress, UPR activation and accumulation of ER lumenal proteins in the cytosol.

Current Projects

Recently, we discovered an adaptive ER quality control system to debulk the ER during stress to restore homeostasis. We named this novel process -ER to CYtosol Signaling- "ERCYS". In cancer cells, constitutive ER stress leads to constitutive protein reflux from the ER to the cytosol. In the cytosol, refluxed proteins gain new functions to inhibit tumor suppressing signaling pathways. ERCYS functions to debulk the ER during protein folding stress, and serves as a mode of communication between the ER and the cytosol. In mammalian cells we found that ERCYS may function in parallel to ERAD, UPR and Pre-emptive Quality Control (Pre-QC) systems to manage the ER protein load. In my lab we are interested in 1. Understand at the molecular level the mechanism that control the reflux of ER lumenal proteins from the ER to the cytosol. 2. Study the pro-cancerous functions of the refluxed proteins in the cytosol and develop genetic and pharmacological strategies to tamper with their new activities in non-ER locations.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Keywords

  • QH301 Biology
  • UPR
  • Proteostasis
  • Endoplasmic Reticulum
  • Cancer
  • ER stress
  • Reflux

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