“MMC is home to a large and diverse community of researchers
with a shared goal of advancing research in human biology.”

About

The Mitochondria and Metabolism Center (MMC) at the University of Washington is home to a large and diverse community of researchers. With an increased recognition that acquired mitochondrial dysfunction is a hallmark of highly prevalent diseases such as obesity/diabetes, cancer, cardiovascular and neurodegenerative diseases, researchers are actively investigating disease processes on a number of fronts. Current studies at the MMC include evaluating the role of impaired fatty acid oxidation mechanisms in heart disease; signaling mechanisms of enzymes in cell metabolism; the role of mitochondrial dysfunction in heart failure; and the role of particular amino acids in developing insulin resistance and heart disease.

Mitochondria and metabolism are closely related disciplines vital to human biology, physiology, and diseases. Current investigations into mitochondria and metabolism fascinate us with the observations that alterations of mitochondrial function and cell metabolism control life span in multiple model organisms, and as such, are emerging as therapeutic targets for a wide variety of diseases.   In response to this challenge, the MMC was established in 2009 by Dr. Rong Tian to explore mitochondrial functioning specifically in cardiac muscle tissue. The center has continued to grow steadily in members, capabilities, research areas and activities, and funding. There are currently over thirty people established at the center, in addition to bringing together multi-disciplinary investigators from across the university and its affiliated institutions to foster interactions and to share resources. We hold monthly research seminars during the academic year as well as hosting a distinguished guest lecture series featuring world-renowned experts in the areas of mitochondria and metabolism.

With over 8000 square feet of lab and office space, state-of-the-art equipment, including the the High Resolution NMR Spectroscopy facility, and the Mass Spectrometry and Microimaging (HRIM) facility, we foster a collaborative work environment. The center is actively engaged in advancing scientific discoveries  to address mitochondrial dysfunction that will lead to improvements in diagnosis and treatment for many conditions that we face in the modern era.

Mission & Values

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Our Research

Energy Metabolism

Energy metabolism is extremely robust in the heart. An adult human heart has the highest oxygen uptake rate in the body (~0.1ml O2/g/min at basal conditions); it generates and consumes (turnover) about 6 Kg of ATP daily, 15-20 times its own weight.  Metabolic reprogramming has been recognized as integral of the pathological remodeling which ultimately leads to heart failure. In addition to its energetic impact, we recently demonstrated that metabolic reprogramming is required for the development of pathological hypertrophy. Our studies aim at identifying and disrupting the molecular mechanisms linking the remodeling of glucose, lipid, and amino acid metabolism to the signaling pathways leading to pathological growth of the cardiac myocytes.

Mitochondria Biology

In addition to be the “powerhouse of the cell”, the mitochondrion is a signaling hub that regulates cell growth, survival and stress responses. Mitochondrial dysfunction has been observed in a variety of disease conditions. There

is, however, no therapy for mitochondrial dysfunction up to date. We recently revealed a critical role of mitochondrial NAD(H) redox state in protein modification and stress tolerance.  We are developing technology platforms with collaborators to investigate subcellular NAD(H) level and protein-protein interactions using novel biosensors and quantitative proteomics. Both basic and clinical research are ongoing to seek the molecular targets and therapeutic applications.

Immunometabolism

Activation of immune cells is associated with global metabolic rewiring.  Proinflammatory activation of macrophage shifts it energy metabolism from oxidative phosphorylation towards glycolysis while transition to reparative macrophage is associated with enhanced oxidative metabolism.  Our study determines whether mitochondrial function plays a driver role in the shift of macrophage metabolism and function, which could identify novel targets for modulation of innate immunity and inflammation.

Stem Cell Metabolism

Mitochondria emerge as an important regulator of cell fate during the development. Multiple mechanisms have been proposed, such as, ROS elicited DNA-damage response, or mitochondrial metabolites for growth and epigenetic modifications. Our studies seek to identify and target mitochondrial mechanisms for promoting the maturation of cells derived from human induced pluripotent stem cells (iPSC). One of our focuses is the communication of mitochondria and other cellular compartments in the regulation of gene transcription and signal transduction.