Vishva M. Dixit, MD, PhD
Genentech, Inc., San Francisco
Vice President of Early Discovery Research
Member, National Academy of Sciences
Foreign Member of the Royal Society (ForMemRS)
Member, National Academy of Medicine
Fellow, American Academy of Arts and Sciences
Foreign Member of the Royal Netherlands Academy of Arts and Sciences
Foreign Member, European Molecular Biology Organization

Zoom Registration Link: https://ubc.zoom.us/meeting/register/u5Eqcu2orjouEtXjYCnPN5i4i2cGtmHpH7u8

Why so many ways to die? The non-canonical inflammasome pathway

Proper coordination of cellular metabolism and its integration with immune response is paramount to function of cells, organs, and organisms. The endoplasmic reticulum (ER) is the main site for protein and lipid synthesis, trafficking, and the storage of cellular calcium. Work in our group over the past two decades demonstrated that ER also plays a significant role in adaptation to metabolic fluctuations, adaptation to metabolic challenges, and their integration to immune response. This important “integrated metabolic response” is disrupted by metabolic stress of chronic metabolic diseases such as obesity and diabetes in animal models and humans. Restoration of the ER adaptive folding responses by genetic or chemical means improve metabolic homeostasis in preclinical models and humans. Therefore, understanding the compositional, structural, and functional regulation of the ER and the mechanisms giving rise to its dysfunction remain critical areas of investigation and carry important translational opportunities. In recent studies, we have discovered alteration in structural organization and architecture of the organelle and identified adaptive responses that emanate from the ER during metabolic stress in physiological or pathological contexts. Here, I will present emerging evidence integrating metaflammation to endoplasmic reticulum and mitochondria function and regulation of interactions between organelles during metabolic fluctuations. I will also present our most recent observations on a novel pathway mediated by the NRF family of ER bound transcription factors, which orchestrates previously unknown countermeasures against metabolic stress to preserve ER integrity and metabolic health. Finally, how these molecular mechanisms may be exploited to understand chronic inflammatory diseases and leveraged to design novel and effective preventive and therapeutic strategies will be discussed.

Contact Information: Dr. Ivan Robert Nabi
604-822-7000 ivan.robert.nabi@ubc.ca