Distinguished Scientist Seminar Series featuring Ebru Erbay, MD, PhD – “Organelle Stress in Cardiometabolic Disease”
Distinguished Scientist Seminar Series
Ebru Erbay, MD, PhD
Altos Labs, Bay Area Institute of Science
Title & Abstract:
“Organelle Stress in Cardiometabolic Disease”
Mounting an immune response involves energetically demanding processes such as immune cell proliferation, new protein synthesis (cytokines, chemokines) and phagocytosis. These energetic and biosynthetic demands are accompanied with the rewiring of metabolic pathways and repurposing of metabolic intermediates. The intrinsic metabolic flexibility of immune cells directly influences their effector functions that shape the outcome of the immune response. At the epicenter of this immune and metabolic reprogramming (immunometabolism) are organelles that compartmentalize specific metabolic reactions. While organelles like endoplasmic reticulum (ER) and mitochondria form functionally specialized units, they need to coordinate with each other to provide the metabolic robustness and adaptability needed by the immune cells to transition between activation and resolution phases of inflammation. Consequently, ER and mitochondrial dysfunction are often intertwined in metabolic diseases. In obesity and dyslipidemia, the metabolic overloading of ER and mitochondria can alter immune cell function and trigger the activation of innate immune signaling proteins positioned on their outer membranes. Obesity-driven organelle stress is associated with an unresolving, low-grade inflammation (also known as metaflammation due to its metabolic origin). Metaflammation underlies many pathologies that cluster around obesity, such as diabetes and atherosclerosis, in Cardiometabolic Syndrome (CMS). Our lab is deeply invested in mechanistically understanding and resolving metaflammation and for many years, we have focused on investigating organelle stress that is at the root of metaflammation. In this seminar, I will describe our current mechanistic findings that explain how organelle stress alters immune cell functions relevant to atherosclerosis.