Frederick Maxfield, Ph.D.

Vladimir and Wanda Toscanini Horowitz Professor and Chairman, Department of Biochemistry
Weill Cornell Medical College

Dr. Maxfield has applied quantitative imaging methods to the study of membrane biology. He was among the first to use fluorescence microscopy for quantitative analysis of membrane traffic, which led to fundamental mechanistic insights regarding the endocytic trafficking of proteins and lipids. This included the initial demonstration that endosomes are acidic and that acidification is essential for many endosomal functions. His laboratory also provided much of the initial characterization of a novel organelle, the endocytic recycling compartment. Using cell culture models, he has shown that microglia can internalize plaque material, but they fail to digest it efficiently because they don’t properly acidify their lysosomes. His laboratory now is extending these studies into in vivo measurements of lysosome acidification and digestion of amyloid plaques by microglia.

Funded Research

Project Description Researchers Funding
Regulation of Microglial Lysosome Acidification

Microglia are the main immune cells of the central nervous system. They normally carry out diverse functions, including removal of dead cells and other debris from the brain. Under some circumstances they have been shown to degrade Alzheimer’s disease amyloid plaques in acidic organelles called lysosomes. We have shown that the acidity of microglial lysosomes is controlled by signaling processes, and that resting microglia in cell culture are ineffective at degrading amyloid because of poor lysosome acidification.