Anesthesiology & Pain Medicine >> Research >> Labs >> Tian Lab

Tian Laboratory
Mitochondria and Metabolism Center, UW Medicine South Lake Union

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PI: Rong Tian, MD, PhD

Research Overview

Research in the Tian Laboratory focuses on the role of cell metabolism and mitochondrial function in the pathogenesis of human diseases. The laboratory uses multi-disciplinary approaches to identify novel regulatory mechanisms, perturb the metabolic networks, and interrogate metabolic fluxes and bioenergetics in a variety of model systems. Current studies concentrate on cardiac substrate metabolism, mitochondrial function and metabolic signaling by combining the powerful NMR techniques and metabolomics with ability to target the molecular regulatory mechanisms via genetic manipulation in animal models. Dr. Tian is also interested in bi-directional translational research between the bench and the bedside to elucidate the functional significance of altered cellular metabolism in ischemic heart disease, obesity, diabetes and heart failure.

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 about 6 Kg of ATP daily, 15-20 times its own weight. Even though the heart has developed extensive metabolic machinery and sophisticated regulatory networks to ensure energy homeostasis, impairment of cardiac metabolism has been found in a variety of disease conditions. Importantly, the consequence of abnormal cardiac metabolism is no longer limited to deficient energy production, as the biological roles of mitochondria and reactive oxygen species have been increasingly recognized.

Part of our current research examines the fundamental mechanisms linking altered cardiac metabolism and mitochondrial dysfunction to the pathogenesis of heart diseases. This line of work seeks to generate a basis for metabolic therapy for heart failure and cardiac lipotoxicity in obesity and diabetes. Studies in this direction extend to nutrient-mediated gene expression and programming of the cell during development, aging and disease conditions.

Another focus of our lab is to understand metabolic signaling in cardiovascular biology. We are interested in signaling mechanisms regulating cell metabolism under disease conditions as well as novel signaling functions of metabolites. For example, we were first to report that bioenergetic stress in pathological cardiac hypertrophy activates the AMP-activated protein kinase (AMPK), an energy sensor and master switch of metabolism. We subsequently generated mouse models with "gain-of-function" and "loss-of-function" of AMPK. Ongoing investigations in the lab address novel roles of AMPK in mitochondria biogenesis/function, cell growth and survival.