Weiwei Fan, PhD

Dr. Fan is currently a staff scientist at the Salk Institute for Biological Studies. He was originally trained as a mitochondrial biologist in the laboratory of Dr. Douglas Wallace at the University of California, Irvine, where he created and characterized multiple mouse models that contain mitochondrial DNA (mtDNA) mutations. His work was among the first to establish the contribution of mtDNA mutations to pathological conditions in vivo and demonstrated the presence of a maternal germ-line selection mechanism that eliminates deleterious mtDNA mutations. Upon finishing his PhD training, Dr. Fan shifted his research focus from the mitochondrion into the nucleus and joined the group of Dr. Ronald Evans at the Salk Institute to study how the nucleus controls mitochondrial functions through transcriptional regulations by nuclear hormone receptors. His work at the Salk Institute has identified muscle PPARδ as a master regulator of lipid and glucose metabolism, which upon activation by exercise, induces a shift of the mitochondrial energy substrate utilization from glucose to fatty acid. Using both gain- and loss-of-function mouse models, he has demonstrated that such a PPARδ-dependent energy substrate shift is required to achieve maximal endurance enhancement by exercise training, and that the pharmacological activation of muscle PPARδ mimics exercise in activating the substrate shift and boosting endurance performance. He has also identified the orphan nuclear hormone receptors ERRα and ERRγ as the master transcriptional regulators of mitochondrial energy metabolism, which directly bind to the majority of mitochondrial energetic genes and positively regulate their expression.