Research Topics
| FREDERICK MAXFIELDSummaryAffiliation: Cornell University Country: USA Publications
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Publications
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 apoptosYankun 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...- Role of cholesterol and lipid organization in diseaseFrederick 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... 
Cholesterol, the central lipid of mammalian cellsFrederick R Maxfield
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
Curr Opin Cell Biol 22:422-9. 2010....- Endocytic recyclingFrederick 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... - Intracellular cholesterol transportFrederick R Maxfield
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
J Clin Invest 110:891-8. 2002 - Plasma membrane microdomainsFrederick 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... - Intracellular sterol transport and distributionFrederick 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... - Sterol and lipid trafficking in mammalian cellsF 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... - Lipid and cholesterol trafficking in NPCSushmita 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... - Sterol, protein and lipid trafficking in Chinese hamster ovary cells with Niemann-Pick type C1 defectNina 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... - Effects of cholesterol depletion and increased lipid unsaturation on the properties of endocytic membranesMingming Hao
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
J Biol Chem 279:14171-8. 2004.... - Different transport routes for high density lipoprotein and its associated free sterol in polarized hepatic cellsDaniel 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... - Elevated plasma membrane cholesterol content alters macrophage signaling and functionChunbo Qin
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
Arterioscler Thromb Vasc Biol 26:372-8. 2006..CONCLUSIONS: These findings indicate that increased membrane cholesterol causes dramatic effects on macrophage cellular functions related to the actin cytoskeleton. They should provide new insights into the early steps of atherogenesis... - Automated microscopy screening for compounds that partially revert cholesterol accumulation in Niemann-Pick C cellsNina 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... - Macrophages create an acidic extracellular hydrolytic compartment to digest aggregated lipoproteinsAbigail 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... - Direct observation of rapid internalization and intracellular transport of sterol by macrophage foam cellsDaniel 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... - Sterols are mainly in the cytoplasmic leaflet of the plasma membrane and the endocytic recycling compartment in CHO cellsMousumi 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... - 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 endosomesSharron 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... - Rapid nonvesicular transport of sterol between the plasma membrane domains of polarized hepatic cellsDaniel 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... - Vesicular and non-vesicular sterol transport in living cells. The endocytic recycling compartment is a major sterol storage organelleMingming 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... - Export from pericentriolar endocytic recycling compartment to cell surface depends on stable, detyrosinated (glu) microtubules and kinesinSharron 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... - Intracellular sterol dynamicsBruno 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... - Aggregated LDL in contact with macrophages induces local increases in free cholesterol levels that regulate local actin polymerizationInna Grosheva
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
Arterioscler Thromb Vasc Biol 29:1615-21. 2009.... - Elevated cholesterol levels in the plasma membranes of macrophages inhibit migration by disrupting RhoA regulationTomokazu 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... - Improvement in lipid and protein trafficking in Niemann-Pick C1 cells by correction of a secondary enzyme defectCecilia 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... - Membrane lipid organization is critical for human neutrophil polarizationLynda 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... - Role of cytoplasmic domain serines in intracellular trafficking of furinFlorencia B Schapiro
Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
Mol Biol Cell 15:2884-94. 2004.... - Endocytosis of beta-cyclodextrins is responsible for cholesterol reduction in Niemann-Pick type C mutant cellsAnton 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... - Stearoyl-CoA desaturase inhibits ATP-binding cassette transporter A1-mediated cholesterol efflux and modulates membrane domain structureYu 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... - The cytoplasmic domain of the low density lipoprotein (LDL) receptor-related protein, but not that of the LDL receptor, triggers phagocytosisMintoo 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... - Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrilsAmitabha 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... - Modeling the structure of the StART domains of MLN64 and StAR proteins in complex with cholesterolMarta Murcia
Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10021, USA
J Lipid Res 47:2614-30. 2006.... - Chemical screen to reduce sterol accumulation in Niemann-Pick C disease cells identifies novel lysosomal acid lipase inhibitorsAnton 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... - Thiadiazole carbamates: potent inhibitors of lysosomal acid lipase and potential Niemann-Pick type C disease therapeuticsAnton 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.... - Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: a pathway for late-stage quality controlMeihui 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... - (-)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cellsSeiji 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... - Role of an acidic cluster/dileucine motif in cation-independent mannose 6-phosphate receptor trafficLori 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... - Degradation of fibrillar forms of Alzheimer's amyloid beta-peptide by macrophagesAmitabha 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... - Membrane domainsSushmita 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... - Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesisZahra 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... - Endocytic recycling compartments altered in cisplatin-resistant cancer cellsXing-Jie Liang
Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland, USA
Cancer Res 66:2346-53. 2006.... - SMS overexpression and knockdown: impact on cellular sphingomyelin and diacylglycerol metabolism, and cell apoptosisTinbo 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... - The inhibitory effect of (-)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cellsSeiji 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... - Oxalic acid alters intracellular calcium in endothelial cellsPhoebe 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 Grants
- Receptor-mediated Endocytosis-Mechanism and FunctionFREDERICK 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. ..
- CYSTOLIC-FREE CALCIUM AND CELL MOTILITYFREDERICK 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. ..
- RECEPTOR-MEDIATED ENDOCYTOSIS--MECHANISM AND FUNCTIONFREDERICK MAXFIELD; Fiscal Year: 2004..These studies will lead to an increasingly complete description of endocytic trafficking pathways. ..
- INTERACTIONS BETWEEN MICROGLIA AND BETA AMYLOID PLAQUESFREDERICK 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. ..
- Macrophage-lipoprotein interactionsFrederick 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. ..