FREDERICK MAXFIELD

Summary

Affiliation: Cornell University
Country: USA

Publications

  1. ncbi request reprint Enrichment of endoplasmic reticulum with cholesterol inhibits sarcoplasmic-endoplasmic reticulum calcium ATPase-2b activity in parallel with increased order of membrane lipids: implications for depletion of endoplasmic reticulum calcium stores and apoptos
    Yankun Li
    Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    J Biol Chem 279:37030-9. 2004
  2. ncbi request reprint Role of cholesterol and lipid organization in disease
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Nature 438:612-21. 2005
  3. pmc Cholesterol, the central lipid of mammalian cells
    Frederick R Maxfield
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Curr Opin Cell Biol 22:422-9. 2010
  4. ncbi request reprint Endocytic recycling
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA
    Nat Rev Mol Cell Biol 5:121-32. 2004
  5. pmc Intracellular cholesterol transport
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Clin Invest 110:891-8. 2002
  6. ncbi request reprint Plasma membrane microdomains
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Curr Opin Cell Biol 14:483-7. 2002
  7. ncbi request reprint Intracellular sterol transport and distribution
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Curr Opin Cell Biol 18:379-85. 2006
  8. ncbi request reprint Sterol and lipid trafficking in mammalian cells
    F R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Biochem Soc Trans 34:335-9. 2006
  9. ncbi request reprint Lipid and cholesterol trafficking in NPC
    Sushmita Mukherjee
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Biochim Biophys Acta 1685:28-37. 2004
  10. ncbi request reprint Sterol, protein and lipid trafficking in Chinese hamster ovary cells with Niemann-Pick type C1 defect
    Nina H Pipalia
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Traffic 8:130-41. 2007

Research Grants

  1. Receptor-mediated Endocytosis-Mechanism and Function
    FREDERICK MAXFIELD; Fiscal Year: 2007
  2. CYSTOLIC-FREE CALCIUM AND CELL MOTILITY
    FREDERICK MAXFIELD; Fiscal Year: 2003
  3. RECEPTOR-MEDIATED ENDOCYTOSIS--MECHANISM AND FUNCTION
    FREDERICK MAXFIELD; Fiscal Year: 2004
  4. INTERACTIONS BETWEEN MICROGLIA AND BETA AMYLOID PLAQUES
    FREDERICK MAXFIELD; Fiscal Year: 2004
  5. Macrophage-lipoprotein interactions
    Frederick R Maxfield; Fiscal Year: 2010

Collaborators

Detail Information

Publications44

  1. ncbi request reprint Enrichment of endoplasmic reticulum with cholesterol inhibits sarcoplasmic-endoplasmic reticulum calcium ATPase-2b activity in parallel with increased order of membrane lipids: implications for depletion of endoplasmic reticulum calcium stores and apoptos
    Yankun Li
    Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    J Biol Chem 279:37030-9. 2004
    ..This biophysical model may underlie the critical connection between excess cholesterol, unfolded protein response induction, macrophage death, and plaque destabilization in advanced atherosclerosis...
  2. ncbi request reprint Role of cholesterol and lipid organization in disease
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Nature 438:612-21. 2005
    ..These insights have also led to improved understanding of normal physiology...
  3. pmc Cholesterol, the central lipid of mammalian cells
    Frederick R Maxfield
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Curr Opin Cell Biol 22:422-9. 2010
    ....
  4. ncbi request reprint Endocytic recycling
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA
    Nat Rev Mol Cell Biol 5:121-32. 2004
    ..The molecular basis for many of these sorting processes is only partly understood...
  5. pmc Intracellular cholesterol transport
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Clin Invest 110:891-8. 2002
  6. ncbi request reprint Plasma membrane microdomains
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Curr Opin Cell Biol 14:483-7. 2002
    ..It appears that there are many different types of membrane domains in the plasma membrane, and perhaps the entire membrane should be viewed as a mosaic of microdomains...
  7. ncbi request reprint Intracellular sterol transport and distribution
    Frederick R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Curr Opin Cell Biol 18:379-85. 2006
    ..Recent theoretical and experimental studies indicate ways in which the lipid environment can alter the chemical potential of sterols, which may help to explain aspects of their transport kinetics and distribution...
  8. ncbi request reprint Sterol and lipid trafficking in mammalian cells
    F R Maxfield
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Biochem Soc Trans 34:335-9. 2006
    ..In this review, we present a summary of the current understanding of these aspects of intracellular trafficking and distribution of lipids, and more specifically, of sterols...
  9. ncbi request reprint Lipid and cholesterol trafficking in NPC
    Sushmita Mukherjee
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Biochim Biophys Acta 1685:28-37. 2004
    ..We also discuss some potential therapeutic directions being suggested by recent research...
  10. ncbi request reprint Sterol, protein and lipid trafficking in Chinese hamster ovary cells with Niemann-Pick type C1 defect
    Nina H Pipalia
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Traffic 8:130-41. 2007
    ..These data are consistent with multiple trafficking defects in both early and late endosomes in NPC cells...
  11. ncbi request reprint Effects of cholesterol depletion and increased lipid unsaturation on the properties of endocytic membranes
    Mingming Hao
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 279:14171-8. 2004
    ....
  12. ncbi request reprint Different transport routes for high density lipoprotein and its associated free sterol in polarized hepatic cells
    Daniel Wüstner
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    J Lipid Res 45:427-37. 2004
    ..We conclude that rapid, nonvesicular transport of sterol to the BC and efficient recycling of HDL particles underlies the selective sorting of sterol from HDLs in hepatocytes...
  13. ncbi request reprint Elevated plasma membrane cholesterol content alters macrophage signaling and function
    Chunbo Qin
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Arterioscler Thromb Vasc Biol 26:372-8. 2006
    ..This study was aimed at testing the hypothesis that macrophage behavior is altered when membrane cholesterol levels are elevated, as might be the case for cells in contact with lipoproteins within atherosclerotic lesions...
  14. ncbi request reprint Automated microscopy screening for compounds that partially revert cholesterol accumulation in Niemann-Pick C cells
    Nina H Pipalia
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    J Lipid Res 47:284-301. 2006
    ..These compounds are effective at concentrations of 123 nM to 3 microM in reducing the cholesterol accumulation in cells with a NPC1 phenotype...
  15. pmc Macrophages create an acidic extracellular hydrolytic compartment to digest aggregated lipoproteins
    Abigail S Haka
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Mol Biol Cell 20:4932-40. 2009
    ..A detailed understanding of these processes is essential for developing strategies to prevent atherosclerosis...
  16. ncbi request reprint Direct observation of rapid internalization and intracellular transport of sterol by macrophage foam cells
    Daniel Wüstner
    Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Traffic 6:396-412. 2005
    ..Our results indicate that elevation of sterol levels in Mphis enhances transport of sterol from the plasma membrane by a non-vesicular pathway...
  17. pmc Sterols are mainly in the cytoplasmic leaflet of the plasma membrane and the endocytic recycling compartment in CHO cells
    Mousumi Mondal
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Mol Biol Cell 20:581-8. 2009
    ..This means that cholesterol constitutes approximately 40 mol% of cytoplasmic leaflet lipids, which may have important implications for intracellular cholesterol transport and membrane domain formation...
  18. pmc Endocytosed cation-independent mannose 6-phosphate receptor traffics via the endocytic recycling compartment en route to the trans-Golgi network and a subpopulation of late endosomes
    Sharron X Lin
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Biol Cell 15:721-33. 2004
    ..These data demonstrate that CI-MPR takes a complex route that involves multiple sorting steps in both early and late endosomes...
  19. ncbi request reprint Rapid nonvesicular transport of sterol between the plasma membrane domains of polarized hepatic cells
    Daniel Wüstner
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 277:30325-36. 2002
    ..We conclude that sterol shuttles rapidly among the plasma membrane domains and other membrane organelles and that this nonvesicular pathway includes fast transbilayer migration...
  20. ncbi request reprint Vesicular and non-vesicular sterol transport in living cells. The endocytic recycling compartment is a major sterol storage organelle
    Mingming Hao
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 277:609-17. 2002
    ..We propose that a large portion of intracellular cholesterol is localized in the ERC, and this pool might be important in maintaining cellular cholesterol homeostasis...
  21. pmc Export from pericentriolar endocytic recycling compartment to cell surface depends on stable, detyrosinated (glu) microtubules and kinesin
    Sharron X Lin
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Mol Biol Cell 13:96-109. 2002
    ..These results suggest that stable Glu MTs and kinesin play a role in the organization of the ERC and in facilitating movement of vesicles from the ERC to the cell surface...
  22. pmc Intracellular sterol dynamics
    Bruno Mesmin
    Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
    Biochim Biophys Acta 1791:636-45. 2009
    ..Although still poorly characterized in many trafficking routes, several potential sterol transport proteins have been described in detail; as a result, molecular mechanisms for sterol transport among membranes start to be appreciated...
  23. pmc Aggregated LDL in contact with macrophages induces local increases in free cholesterol levels that regulate local actin polymerization
    Inna Grosheva
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Arterioscler Thromb Vasc Biol 29:1615-21. 2009
    ....
  24. ncbi request reprint Elevated cholesterol levels in the plasma membranes of macrophages inhibit migration by disrupting RhoA regulation
    Tomokazu Nagao
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Arterioscler Thromb Vasc Biol 27:1596-602. 2007
    ..We tested the hypothesis that elevated membrane cholesterol levels, which may result from interactions with aggregated LDL, affect macrophage migration...
  25. pmc Improvement in lipid and protein trafficking in Niemann-Pick C1 cells by correction of a secondary enzyme defect
    Cecilia Devlin
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Traffic 11:601-15. 2010
    ..These data show that correcting one aspect of a complex lysosomal lipid storage disease can reduce the cellular consequences even if the primary genetic defect is not corrected...
  26. ncbi request reprint Membrane lipid organization is critical for human neutrophil polarization
    Lynda M Pierini
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Biol Chem 278:10831-41. 2003
    ..Collectively, these findings support a model in which the plasma membrane is organized into domains that aid in amplifying the chemoattractant gradient and maintaining cell polarization...
  27. pmc Role of cytoplasmic domain serines in intracellular trafficking of furin
    Florencia B Schapiro
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Biol Cell 15:2884-94. 2004
    ....
  28. pmc Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cells
    Anton I Rosenbaum
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:5477-82. 2010
    ..These findings suggest that cyclodextrin-mediated enhanced cholesterol transport from the endocytic system can reduce cholesterol accumulation in cells with defects in either NPC1 or NPC2...
  29. ncbi request reprint Stearoyl-CoA desaturase inhibits ATP-binding cassette transporter A1-mediated cholesterol efflux and modulates membrane domain structure
    Yu Sun
    Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 278:5813-20. 2003
    ..ABCA1-mediated cholesterol and phospholipid efflux may be uncoupled in pathological states associated with high SCD activity, as in hyperinsulinemic obese mice, or in animals treated with LXR activators...
  30. ncbi request reprint The cytoplasmic domain of the low density lipoprotein (LDL) receptor-related protein, but not that of the LDL receptor, triggers phagocytosis
    Mintoo Patel
    Department of Medicine, Columbia University, New York, New York 10032, USA
    J Biol Chem 278:44799-807. 2003
    ..These findings have important implications for atherogenesis and apoptotic cell clearance and for a fundamental cell biological understanding of how the LDL receptor and LRP function in internalization processes...
  31. pmc Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils
    Amitabha Majumdar
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Mol Biol Cell 18:1490-6. 2007
    ..Our results indicate that regulated lysosomal acidification can potentiate fAbeta degradation by microglia...
  32. ncbi request reprint Modeling the structure of the StART domains of MLN64 and StAR proteins in complex with cholesterol
    Marta Murcia
    Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10021, USA
    J Lipid Res 47:2614-30. 2006
    ....
  33. pmc Chemical screen to reduce sterol accumulation in Niemann-Pick C disease cells identifies novel lysosomal acid lipase inhibitors
    Anton I Rosenbaum
    Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
    Biochim Biophys Acta 1791:1155-65. 2009
    ..This work demonstrates the utility of phenotypic cellular screens as a means to identify molecular targets for altering a complex process such as intracellular cholesterol trafficking and metabolism...
  34. pmc Thiadiazole carbamates: potent inhibitors of lysosomal acid lipase and potential Niemann-Pick type C disease therapeutics
    Anton I Rosenbaum
    Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA
    J Med Chem 53:5281-9. 2010
    ....
  35. pmc Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality control
    Meihui Pan
    Departments of Medicine, Leon H Charney Division of Cardiology, and Cell Biology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 105:5862-7. 2008
    ..In summary, apoB secretory control via PERPP/autophagosomes is likely a key component of normal and pathologic regulation of plasma apoB levels, as well as a means for remarkably late-stage quality control of a secreted protein...
  36. pmc (-)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cells
    Seiji Adachi
    Herbert Irving Comprehensive Cancer Center and Department of Medicine, Columbia University Medical Center, HHSC 1509, 701 West 168th Street, New York, NY 10032 2704, USA
    Carcinogenesis 29:1986-93. 2008
    ..This sequestrating of inactivated EGFRs into endosomes may explain, at least in part, the ability of EGCG to inhibit activation of the EGFR and thereby exert anticancer effects...
  37. ncbi request reprint Role of an acidic cluster/dileucine motif in cation-independent mannose 6-phosphate receptor traffic
    Lori L Tortorella
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Traffic 8:402-13. 2007
    ..These results demonstrate that the acidic cluster/dileucine motif of CI-MPR is critical for receptor sorting at early stages of intracellular transport following endocytosis...
  38. pmc Degradation of fibrillar forms of Alzheimer's amyloid beta-peptide by macrophages
    Amitabha Majumdar
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, United States
    Neurobiol Aging 29:707-15. 2008
    ..These results indicate that initial proteolysis near the N-terminus is similar in both cell types, but microglia are limited in their ability to make further cuts in the fAbeta...
  39. ncbi request reprint Membrane domains
    Sushmita Mukherjee
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Annu Rev Cell Dev Biol 20:839-66. 2004
    ..We discuss the current analyses of the properties and function of membrane domains in cells and compare their properties with chemically simpler model membrane systems that can be understood in greater detail...
  40. ncbi request reprint Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis
    Zahra Mamdouh
    Department of Pathology and Laboratory Medicine, Weill Medical College, 1300 York Avenue, New York, New York 10021, USA
    Nature 421:748-53. 2003
    ..In addition, blockade of TEM with antibodies against PECAM specifically blocks the recruitment of this membrane to the zones of leukocyte migration, without affecting the constitutive membrane trafficking...
  41. pmc Endocytic recycling compartments altered in cisplatin-resistant cancer cells
    Xing Jie Liang
    Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA
    Cancer Res 66:2346-53. 2006
    ....
  42. ncbi request reprint SMS overexpression and knockdown: impact on cellular sphingomyelin and diacylglycerol metabolism, and cell apoptosis
    Tinbo Ding
    Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
    J Lipid Res 49:376-85. 2008
    ..These results indicate that SMS1 and SMS2 are key factors in the control of SM and DAG levels within the cell and thus influence apoptosis...
  43. ncbi request reprint The inhibitory effect of (-)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells
    Seiji Adachi
    Herbert Irving Comprehensive Cancer Center and Department of Medicine, Columbia University Medical Center, New Yourk, NY 10032 2704, USA
    Cancer Res 67:6493-501. 2007
    ..These effects may also explain the ability of EGCG to inhibit activation of other membrane-associated RTKs, and they may play a critical role in the anticancer effects of this and related compounds...
  44. ncbi request reprint Oxalic acid alters intracellular calcium in endothelial cells
    Phoebe A Recht
    Leon H Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA
    Atherosclerosis 173:321-8. 2004
    ..We conclude that plasma oxalate exerts its atherogenic effects by elevating intracellular calcium exclusively in endothelial cells and preventing re-endothelialization...

Research Grants23

  1. Receptor-mediated Endocytosis-Mechanism and Function
    FREDERICK MAXFIELD; Fiscal Year: 2007
    ..A novel mechanism by which unsaturated fatty acids alter the trafficking of the sterol response element binding protein will be characterized. ..
  2. CYSTOLIC-FREE CALCIUM AND CELL MOTILITY
    FREDERICK MAXFIELD; Fiscal Year: 2003
    ..Finally, the role of myosin and of oriented recycling will be examined in neutrophils migrating through endothelial cell monolayers and through natural biological matrices, which resemble the physiological sites of neutrophil function. ..
  3. RECEPTOR-MEDIATED ENDOCYTOSIS--MECHANISM AND FUNCTION
    FREDERICK MAXFIELD; Fiscal Year: 2004
    ..These studies will lead to an increasingly complete description of endocytic trafficking pathways. ..
  4. INTERACTIONS BETWEEN MICROGLIA AND BETA AMYLOID PLAQUES
    FREDERICK MAXFIELD; Fiscal Year: 2004
    ..We will analyze the mechanisms of degradation of AB amyloid in microglia and also determine whether soluble AB peptides become incorporated into insoluble AB in the endosomes and lysosomes of microglia. ..
  5. Macrophage-lipoprotein interactions
    Frederick R Maxfield; Fiscal Year: 2010
    ..Research findings based on these studies may lead to new treatments to prevent or reverse the formation of atherosclerotic lesions. ..