Juan Cubillos-Ruiz

Mounting optimal immune responses against malignant cells and pathogens requires high levels of protein synthesis, folding, modification, and trafficking in leukocytes, which are processes coordinated by the endoplasmic reticulum (ER). However, diverse extracellular and intracellular conditions can affect the protein-handling capacity of this organelle, inducing a state of ‘ER stress’ that activates the unfolded protein response (UPR).  Our research has provided key insights into the role of ER stress response pathways in immunity, revealing its context-dependent impact on immune cell metabolism, function, and fate. We uncovered that activation of ER stress sensors can stimulate lipogenesis and prostaglandin biosynthesis in myeloid cells. Further, we established that in T cells experiencing nutrient restriction, the activation of ER stress sensors can regulate mitochondrial function and bioenergetics. Dysregulation of the UPR in immune cells can therefore contribute to various pathologies such as cancer, chronic pain, autoimmunity, inflammation, and metabolic disorders. Targeting abnormal ER stress responses has emerged as a promising approach to control or restore immune cell function in diverse pathological conditions. Our laboratory is interested in answering multiple questions relevant to the role of ER stress in immunity, with an emphasis on defining how the tumor microenvironment causes ER stress in multiple cell populations to evade immune control.  

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