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Research: Lipoprotein Lipase, Heart Disease, CryoEM, Drug Discovery, Enzymology, ANGPTL4, Lipids, Structural Biology

Associate Professor of Biochemistry and Biophysics
(PhD – M.I.T)

ACCEPTING STUDENTS

CSHL TRAINED MENTOR

standard safe zone training

HONORS & AWARDS

  • National Lipid Assoc. Jr. Faculty Research Award: 2017
  • Kavli Fellow: 2014
  • Pew Scholar in the Biomedical Sciences: 2012
  • NIHK99/R00 Pathway to Independence Award: 2010
  • Jane Coffin Childs Fellow: 2006

RESEARCH SUMMARY

Lipoprotein lipase (LPL) breaks down fats so that they can be cleared from the blood. Individuals with LPL deficiency have no way to clear the fats from their blood and therefore develop severe hypertriglyceridemia. LPL is a very high-maintenance enzyme as it needs special assistance to fold into its active form and travel out of cells to the blood. In my lab we use protein biochemistry and cell biology to study these processes.

Our bodies need to be able to increase or decrease LPL activity in order to respond to the amount of fat that is available. This is accomplished through the action of LPL activators and inhibitors. We seek to understand the mechanisms by which these activators and inhibitors affect LPL activity. Doing so will guide the development of new therapies to treat lipid disorders.

SELECTED PUBLICATIONS

Characterization of lipoprotein lipase storage vesicles in 3T3-L1 adipocytes. Roberts BS, Yang CQ, Neher SB. J Cell Sci. 2022 Mar 1;135(5):jcs258734. doi: 10.1242/jcs.258734. Epub 2021 Aug 12.
PMID: 34382637 Free PMC article.

Comparison of angiopoietin-like protein 3 and 4 reveals structural and mechanistic similarities.
Gunn KH, Gutgsell AR, Xu Y, Johnson CV, Liu J, Neher SB. J Biol Chem. 2021 Jan-Jun;296:100312. doi: 10.1016/j.jbc.2021.100312. Epub 2021 Jan 20. PMID: 33482195 Free PMC article.

The structure of helical lipoprotein lipase reveals an unexpected twist in lipase storage.
Gunn KH, Roberts BS, Wang F, Strauss JD, Borgnia MJ, Egelman EH, Neher SB. Proc Natl Acad Sci U S A. 2020 May 12;117(19):10254-10264. doi: 10.1073/pnas.1916555117. Epub 2020 Apr 24. PMID: 32332168 Free PMC article.

A dual apolipoprotein C-II mimetic-apolipoprotein C-III antagonist peptide lowers plasma triglycerides.
Wolska A, Lo L, Sviridov DO, Pourmousa M, Pryor M, Ghosh SS, Kakkar R, Davidson M, Wilson S, Pastor RW, Goldberg IJ, Basu D, Drake SK, Cougnoux A, Wu MJ, Neher SB, Freeman LA, Tang J, Amar M, Devalaraja M, Remaley AT. Sci Transl Med. 2020 Jan 29;12(528):eaaw7905. doi: 10.1126/scitranslmed.aaw7905. PMID: 31996466 Free PMC article.

Endoplasmic reticulum quality control in lipoprotein metabolism.
Koerner CM, Roberts BS, Neher SB. Mol Cell Endocrinol. 2019 Dec 1;498:110547. doi: 10.1016/j.mce.2019.110547. Epub 2019 Aug 20. PMID: 31442546 Free PMC article. Review.

Withdrawal: Lipase maturation factor LMF1, membrane topology and interaction with lipase proteins in the endoplasmic reticulum.
Doolittle MH, Neher SB, Ben-Zeev O, Ling-Liao J, Gallagher CM, Hosseini M, Yin F, Wong H, Walter P, Péterfy M. J Biol Chem. 2019 Aug 9;294(32):12263. doi: 10.1074/jbc.W119.010212.
PMID: 31399538 Free PMC article. No abstract available.

Protecting activity of desiccated enzymes. Piszkiewicz S, Gunn KH, Warmuth O, Propst A, Mehta A, Nguyen KH, Kuhlman E, Guseman AJ, Stadmiller SS, Boothby TC, Neher SB, Pielak GJ.
Protein Sci. 2019 May;28(5):941-951. doi: 10.1002/pro.3604. Epub 2019 Mar 30. PMID: 30868674 Free PMC article.

Mapping the sites of the lipoprotein lipase (LPL)-angiopoietin-like protein 4 (ANGPTL4) interaction provides mechanistic insight into LPL inhibition. Gutgsell AR, Ghodge SV, Bowers AA, Neher SB.
J Biol Chem. 2019 Feb 22;294(8):2678-2689. doi: 10.1074/jbc.RA118.005932. Epub 2018 Dec 27. PMID: 30591589 Free PMC article.

Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity. Wu MJ, Wolska A, Roberts BS, Pearson EM, Gutgsell AR, Remaley AT, Neher SB. J Lipid Res. 2018 Dec;59(12):2456-2465. doi: 10.1194/jlr.D086793. Epub 2018 Oct 14. PMID: 30318473 Free PMC article.

Lipase maturation factor 1 affects redox homeostasis in the endoplasmic reticulum. Roberts BS, Babilonia-Rosa MA, Broadwell LJ, Wu MJ, Neher SB. EMBO J. 2018 Oct 1;37(19):e97379. doi: 10.15252/embj.201797379. Epub 2018 Aug 1. PMID: 30068531 Free PMC article.

Link to all pubs

Saskia Neher