Frederick R. Maxfield

About

Frederick R. Maxfield, Ph.D., is a Professor of Biochemistry and Biophysics at Weill Cornell Medicine. His laboratory studies the basic cell biology of membrane traffic and its application to understanding and treating diseases. Current research interests include cholesterol transport, control of lysosomal pH, and extracellular degradation of large objects such as amyloid, dead adipocytes, or deposits of lipoproteins by macrophages. These studies are related to diseases including atherosclerosis, Alzheimer’s disease, and Niemann-Pick C disease. The Maxfield laboratory focuses on elucidating the mechanisms of extracellular digestion of aggregated LDL (exophagy) and the signaling processes involved in membrane trafficking.

Research topics

• Neuroscience
• Biology
• Biophysics
• Pathology
• Biochemistry
• Genetics
• Chemistry
• Immunology
• Cell biology
• Psychology

Selected publications

• Cholesterol and matrisome pathways dysregulated in astrocytes and microglia

  Cell · 2022 · 394 citations

  PublisherOA PDFDOI

• A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination

  Brain · 2020 · 51 citations

  TMEM106B encodes a lysosomal membrane protein and was initially identified as a risk factor for frontotemporal lobar degeneration. Recently, a dominant D252N mutation in TMEM106B was shown to cause hypomyelinating leukodystrophy. However, how TMEM106B regulates myelination is still unclear. Here we show that TMEM106B is expressed and localized to the lysosome compartment in oligodendrocytes. TMEM106B deficiency in mice results in myelination defects with a significant reduction of protein levels…

  PublisherOA PDFDOI

• Stable reduction of STARD4 alters cholesterol regulation and lipid homeostasis

  Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · 2020-01-07 · 31 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Microglia degrade Alzheimer’s amyloid-beta deposits extracellularly via digestive exophagy

  Cell Reports · 2024-12-01 · 27 citations

  articleOpen accessCorresponding

  How microglia digest Alzheimer’s fibrillar amyloid-beta (Aβ) plaques that are too large to be phagocytosed is not well understood. Here, we show that primary microglial cells create acidic extracellular compartments, lysosomal synapses, on model plaques and digest them with exocytosed lysosomal enzymes. This mechanism, called digestive exophagy, is confirmed by electron microscopy in 5xFAD mouse brains, which shows that a lysosomal enzyme, acid phosphatase, is secreted toward the plaques in stru…

  PublisherDOI

• The formation and consequences of cholesterol-rich deposits in atherosclerotic lesions

  Frontiers in Cardiovascular Medicine · 2023-02-28 · 23 citations

  reviewOpen access1st authorCorresponding

  Cardiovascular diseases remain the leading cause of death throughout the world. Accumulation of lipoprotein-associated lipids and their interaction with macrophages are early steps in the development of atherosclerotic lesions. For decades, it has been known that aggregates of lipoproteins in the subendothelial space are found in early plaques, and these aggregates are tightly associated with extracellular matrix fibers. Additionally, most of the cholesterol in these subendothelial aggregates is…

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM034770

  NIH · $3.6M · 2005

• A Phase 1 Dose Escalation Study of Vorinostat in Niemann-Pick C1 Disease

  NIH · $1.2M · 2014–2016

• Intracellular Cholesterol Transport

  NIH · $1.4M · 2018–2022

Frequent coauthors

• David B. Iaea

  Cornell University

  88 shared

• Ira Tabas

  Columbia University Irving Medical Center

  52 shared

• Lynda M. Pierini

  46 shared

• Sushmita Mukherjee

  43 shared

• Stéphanie Seveau

  The Ohio State University

  43 shared

• H. U. Keller

  University of Bern

  41 shared

• Lise Halbwachs‐Mecarelli

  Hôpital Necker-Enfants Malades

  41 shared

• Friedrich Piller

  Centre National de la Recherche Scientifique

  41 shared

Labs

• Maxfield LabPI

Education

• BS, Chemistry

  Union College

  1971

Similar researchers at Cornell University

• David Eliezerh-66
• Timothy McGrawh-65
• Anant Menonh-60