Publications

Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics. 

Finicle BT, Eckenstein KH, Revenko AS, Anderson BA, Wan WB, McCracken AN, Gil D, Fruman DA, Hanessian S, Seth PP, Edinger AL.

Nucleic Acids Res. 2023 Feb 2:gkad023. doi: 10.1093/nar/gkad023. PMID: 36727438


Drug-like sphingolipid SH-BC-893 opposes ceramide-induced mitochondrial fission and corrects diet-induced obesity. ()

Jayashankar V, Selwan E, Hancock SE, Verlande A, Goodson MO, Eckenstein KH, Milinkeviciute G, Hoover BM, Chen B, Fleischman AG, Cramer KS, Hanessian S, Masri S, Turner N, Edinger AL.

EMBO Mol Med. 2021 Aug 9;13(8):e13086. PMID: 34231322  Epub 2021 Jul 7.

Related News and Views:
Fuse your mitochondria, lose appetite: an anorexic, anti-obesity sphingolipid (https://www.embopress.org/doi/full/10.15252/emmm.202114618)

Carolin Muley and Alexander Bartelt

EMBO Mol Med (2021)13:e14618https://doi.org/10.15252/emmm.202114618

Scientific press: https://www.genengnews.com/news/new-drug-corrects-diet-induced-obesity-by-keeping-mitochondria-from-fragmenting/

 

 

 

Synthetic Sphingolipids with 1,2-Pyridazine Appendages Improve Antiproliferative Activity in Human Cancer Cell Lines.

Bachollet SPJT, Vece V, McCracken AN, Finicle BT, Selwan E, Ben Romdhane N, Dahal A, Ramirez C, Edinger AL, Hanessian S.

ACS Med Chem Lett. 2020 Feb 12;11(5):686-690. doi: 10.1021/acsmedchemlett.9b00553. eCollection 2020 May 14. PMID: 32435371

 

Macropinocytosis confers resistance to therapies targeting cancer anabolism.

Jayashankar V, Edinger AL.

Nat Commun. 2020 Feb 28;11(1):1121. doi: 10.1038/s41467-020-14928-3. PMID: 32111826

Highlighted here: https://news.uci.edu/2020/03/03/starve-a-tumor-feed-a-cell-how-cancers-can-resist-drugs/

 

Biocompatible Chemotherapy for Leukemia by Acid-Cleavable, PEGylated FTY720.

Kemp JA, Keebaugh A, Edson JA, Chow D, Kleinman MT, Chew YC, McCracken AN, Edinger AL, Kwon YJ. Bioconjug Chem. 2020 Mar 18;31(3):673-684. doi: 10.1021/acs.bioconjchem.9b00822. Epub 2020 Jan 27.PMID: 31986014

 

Design, synthesis and anticancer activity of constrained sphingolipid-phenoxazine/phenothiazine hybrid constructs targeting protein phosphatase 2A.

Garsi JB, Vece V, Sernissi L, Auger-Morin C, Hanessian S, McCracken AN, Selwan E, Ramirez C, Dahal A, Romdhane NB, Finicle BT, Edinger AL.

Bioorg Med Chem Lett. 2019 Sep 15;29(18):2681-2685. doi: 10.1016/j.bmcl.2019.07.023. Epub 2019 Jul 19.PMID: 31383588

 

Dynamic phosphoproteomics uncovers signaling pathways modulated by anti-neoplastic sphingolipid analogs.

Kubiniok P, Finicle BT, Piffaretti F, McCracken AN, Perryman M, Hanessian S, Edinger AL, Thibault P.

Mol Cell Proteomics. 2018 Nov 27. pii: mcp.RA118.001053. doi: 10.1074/mcp.RA118.001053. PMID: 30482847

 

In search of constrained FTY720 and phytosphingosine analogs as dual acting anticancer agents targeting metabolic and epigenetic pathways.

Garsi JB, Sernissi L, Vece V, Hanessian S, McCracken AN, Simitian G, Edinger AL.

Eur J Med Chem. 2018 Nov 5;159:217-242. doi: 10.1016/j.ejmech.2018.09.043. Epub 2018 Sep 21. PMID: 30292898

 

Starving PTEN-deficient prostate cancer cells thrive under nutrient stress by scavenging corpses for their supper.

Jayashankar V, Finicle BT, Edinger AL.

Mol Cell Oncol. 2018 Aug 17;5(4):e1472060. doi: 10.1080/23723556.2018.1472060. eCollection 2018. PMID: 30250923

 

Nutrient scavenging in cancer.

Finicle BT, Jayashankar V, Edinger AL.

Nat Rev Cancer. 2018 Oct;18(10):619-633. doi: 10.1038/s41568-018-0048-x. Review. PMID: 30097614

 

Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.

Finicle BT, Ramirez MU, Liu G, Selwan EM, McCracken AN, Yu J, Joo Y, Nguyen J, Ou K, Roy SG, Mendoza VD, Corrales DV, Edinger AL.

J Cell Sci. 2018 Jun 25;131(12). pii: jcs213314. doi: 10.1242/jcs.213314. PMID: 29848659

 

PTEN Deficiency and AMPK Activation Promote Nutrient Scavenging and Anabolism in Prostate Cancer Cells.

Kim SM, Nguyen TT, Ravi A, Kubiniok P, Finicle BT, Jayashankar V, Malacrida L, Hou J, Robertson J, Gao D, Chernoff J, Digman MA, Potma EO, Tromberg BJ, Thibault P, Edinger AL.

Cancer Discov. 2018 Jul;8(7):866-883. doi: 10.1158/2159-8290.CD-17-1215. Epub 2018 Mar 23. PMID: 29572236

 

Highlighted in:


Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation.

McCracken AN, McMonigle RJ, Tessier J, Fransson R, Perryman MS, Chen B, Keebaugh A, Selwan E, Barr SA, Kim SM, Roy SG, Liu G, Fallegger D, Sernissi L, Brandt C, Moitessier N, Snider AJ, Clare S, Müschen M, Huwiler A, Kleinman MT, Hanessian S, Edinger AL.

Leukemia. 2017 Mar;31(3):669-677. doi: 10.1038/leu.2016.244. Epub 2016 Aug 30. PMID: 27573555


Branched chain amino acid metabolism and cancer: the importance of keeping things in context.

Selwan EM, Edinger AL.

Transl Cancer Res. 2017 May;6(Suppl 3):S578-S584. doi: 10.21037/tcr.2017.05.05. PMID: 30613481

 

Rab7-a novel redox target that modulates inflammatory pain processing.

Kallenborn-Gerhardt W, Möser CV, Lorenz JE, Steger M, Heidler J, Scheving R, Petersen J, Kennel L, Flauaus C, Lu R, Edinger AL, Tegeder I, Geisslinger G, Heide H, Wittig I, Schmidtko A.

Pain. 2017 Jul;158(7):1354-1365. doi: 10.1097/j.pain.0000000000000920. PMID: 28394828

 

Oligodendroglial deletion of ESCRT-I component TSG101 causes spongiform encephalopathy.

Walker WP, Oehler A, Edinger AL, Wagner KU, Gunn TM.

Biol Cell. 2016 Nov;108(11):324-337. doi: 10.1111/boc.201600014. Epub 2016 Aug 23. PMID: 27406702

 

Vps34 regulates Rab7 and late endocytic trafficking through recruitment of the GTPase-activating protein Armus.

Jaber N, Mohd-Naim N, Wang Z, DeLeon JL, Kim S, Zhong H, Sheshadri N, Dou Z, Edinger AL, Du G, Braga VM, Zong WX.

J Cell Sci. 2016 Dec 1;129(23):4424-4435. Epub 2016 Oct 28. PMID: 27793976

 

Targeting cancer metabolism by simultaneously disrupting parallel nutrient access pathways.

Kim SM, Roy SG, Chen B, Nguyen TM, McMonigle RJ, McCracken AN, Zhang Y, Kofuji S, Hou J, Selwan E, Finicle BT, Nguyen TT, Ravi A, Ramirez MU, Wiher T, Guenther GG, Kono M, Sasaki AT, Weisman LS, Potma EO, Tromberg BJ, Edwards RA, Hanessian S, Edinger AL.

J Clin Invest. 2016 Nov 1;126(11):4088-4102. doi: 10.1172/JCI87148. Epub 2016 Sep 26. PMID: 27669461

 

JCI Author’s take: https://www.youtube.com/watch?v=Ny53-vBFLpY

 

Effects of stereochemistry, saturation, and hydrocarbon chain length on the ability of synthetic constrained azacyclic sphingolipids to trigger nutrient transporter down-regulation, vacuolation, and cell death.

Perryman MS, Tessier J, Wiher T, O’Donoghue H, McCracken AN, Kim SM, Nguyen DG, Simitian GS, Viana M, Rafelski S, Edinger AL, Hanessian S.

Bioorg Med Chem. 2016 Sep 15;24(18):4390-4397. doi: 10.1016/j.bmc.2016.07.038. Epub 2016 Jul 18. PMID: 27475534

 

Age-related myelin degradation burdens the clearance function of microglia during aging.

Safaiyan S, Kannaiyan N, Snaidero N, Brioschi S, Biber K, Yona S, Edinger AL, Jung S, Rossner MJ, Simons M.

Nat Neurosci. 2016 Aug;19(8):995-8. doi: 10.1038/nn.4325. Epub 2016 Jun 13. PMID: 27294511

 

Highlighted in:

Attacking the supply wagons to starve cancer cells to death.

Selwan EM, Finicle BT, Kim SM, Edinger AL.

FEBS Lett. 2016 Apr;590(7):885-907. doi: 10.1002/1873-3468.12121. Epub 2016 Mar 22. Review. PMID: 26938658

 

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

Klionsky DJ, . . . , , Edinger AL, . . . , and Zughaier SM.

Autophagy. 2016;12(1):1-222. doi: 10.1080/15548627.2015.1100356. No abstract available. Erratum in: Autophagy. 2016;12(2):443. Selliez, Iban [corrected to Seiliez, Iban]. PMID: 26799652

 

Azacyclic FTY720 Analogues That Limit Nutrient Transporter Expression but Lack S1P Receptor Activity and Negative Chronotropic Effects Offer a Novel and Effective Strategy to Kill Cancer Cells in Vivo.

Chen B, Roy SG, McMonigle RJ, Keebaugh A, McCracken AN, Selwan E, Fransson R, Fallegger D, Huwiler A, Kleinman MT, Edinger AL, Hanessian S.

ACS Chem Biol. 2016 Feb 19;11(2):409-14. doi: 10.1021/acschembio.5b00761. Epub 2015 Dec 14. PMID: 26653336

 Targeting cancer metabolism at the plasma membrane by limiting amino acid access through SLC6A14.

McCracken AN, Edinger AL.

Biochem J. 2015 Sep 15;470(3):e17-9. doi: 10.1042/BJ20150721.PMID: 26341486

 

Nitric Oxide Synthase as a Target for Methicillin-Resistant Staphylococcus aureus.

Holden JK, Kang S, Beasley FC, Cinelli MA, Li H, Roy SG, Dejam D, Edinger AL, Nizet V, Silverman RB, Poulos TL.

Chem Biol. 2015 Jun 18;22(6):785-92. doi: 10.1016/j.chembiol.2015.05.013. PMID: 26091171

 

B cell Rab7 mediates induction of activation-induced cytidine deaminase expression and class-switching in T-dependent and T-independent antibody responses.

Pone EJ, Lam T, Lou Z, Wang R, Chen Y, Liu D, Edinger AL, Xu Z, Casali P.

J Immunol. 2015 Apr 1;194(7):3065-78. doi: 10.4049/jimmunol.1401896. Epub 2015 Mar 4. PMID: 25740947

 

Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya).

Fransson R, McCracken AN, Chen B, McMonigle RJ, Edinger AL, Hanessian S.

ACS Med Chem Lett. 2013 Oct 10;4(10). doi: 10.1021/ml4002425. PMID: 24273632

 

Reciprocal effects of rab7 deletion in activated and neglected T cells.

Roy SG, Stevens MW, So L, Edinger AL.

Autophagy. 2013 Jul;9(7):1009-23. doi: 10.4161/auto.24468. Epub 2013 Apr 15. PMID: 23615463

 

Loss of TSC2 confers resistance to ceramide and nutrient deprivation.

Guenther GG, Liu G, Ramirez MU, McMonigle RJ, Kim SM, McCracken AN, Joo Y, Ushach I, Nguyen NL, Edinger AL.

Oncogene. 2014 Apr 3;33(14):1776-87. doi: 10.1038/onc.2013.139. Epub 2013 Apr 22. PMID: 23604129

 

Nutrient transporters: the Achilles’ heel of anabolism.

McCracken AN, Edinger AL.

Trends Endocrinol Metab. 2013 Apr;24(4):200-8. doi: 10.1016/j.tem.2013.01.002. Epub 2013 Feb 8. Review. PMID: 23402769

 

Guidelines for the use and interpretation of assays for monitoring autophagy.

Klionsky DJ, . . ., Edinger AL, . . . Zuckerbraun B.

Autophagy. 2012 Apr;8(4):445-544. PMID: 22966490

 

Flow injection tandem mass spectrometric measurement of ceramides of multiple chain lengths in biological samples.

Chen J, Narayan SB, Edinger AL, Bennett MJ.

J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Feb 1;883-884:136-40. doi: 10.1016/j.jchromb.2011.11.017. Epub 2011 Nov 18. PMID: 22138588

 

Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins.

Romero Rosales K, Singh G, Wu K, Chen J, Janes MR, Lilly MB, Peralta ER, Siskind LJ, Bennett MJ, Fruman DA, Edinger AL.

Biochem J. 2011 Oct 15;439(2):299-311. doi: 10.1042/BJ20110853. PMID: 21767261

 

Higlighted in:

 

Unequal in the absence of death: a novel screen identifies cytotoxic compounds selective for cells with activated Akt.

Edinger AL.

Cancer Biol Ther. 2010 Dec 15;10(12):1262-5. Epub 2010 Dec 15. No abstract available. PMID: 20935459

 

The complex interplay between autophagy, apoptosis, and necrotic signals promotes T-cell homeostasis.

Walsh CM, Edinger AL.

Immunol Rev. 2010 Jul;236:95-109. doi: 10.1111/j.1600-065X.2010.00919.x. Review. PMID: 20636811

 

Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence.

Peralta ER, Martin BC, Edinger AL.

J Biol Chem. 2010 May 28;285(22):16814-21. doi: 10.1074/jbc.M110.111633. Epub 2010 Apr 2. PMID: 20363736

 

The BCL-2 protein BAK is required for long-chain ceramide generation during apoptosis.

Siskind LJ, Mullen TD, Romero Rosales K, Clarke CJ, Hernandez-Corbacho MJ, Edinger AL, Obeid LM.

J Biol Chem. 2010 Apr 16;285(16):11818-26. doi: 10.1074/jbc.M109.078121. Epub 2010 Feb 18. PMID: 20172858

 

Death by design: apoptosis, necrosis and autophagy.

Edinger AL, Thompson CB.

Curr Opin Cell Biol. 2004 Dec;16(6):663-9. Review. PMID: 15530778

 

An activated mTOR mutant supports growth factor-independent, nutrient-dependent cell survival.

Edinger AL, Thompson CB.

Oncogene. 2004 Jul 22;23(33):5654-63. PMID: 15133498

 

Defective autophagy leads to cancer.

Edinger AL, Thompson CB.

Cancer Cell. 2003 Dec;4(6):422-4. Review. PMID:14706333

 

Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells.

Edinger AL, Linardic CM, Chiang GG, Thompson CB, Abraham RT.

Cancer Res. 2003 Dec 1;63(23):8451-60. PMID: 14679009

 

Rab7 prevents growth factor-independent survival by inhibiting cell-autonomous nutrient transporter expression.

Edinger AL, Cinalli RM, Thompson CB.

Dev Cell. 2003 Oct;5(4):571-82. PMID: 14536059

 

Higlighted in:

  • APOPTOSIS: Starved to Death (2002). Sci. STKE, Vol. 2002, Issue 143, pp. tw271.
  • MD Snider (2003). A role for Rab7 GTPase in growth factor-regulated cell nutrition and apoptosis.  Cell 12:796-797. https://www.ncbi.nlm.nih.gov/pubmed/14580329

 

Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake.

Edinger AL, Thompson CB.

Mol Biol Cell. 2002 Jul;13(7):2276-88. PMID: 12134068

 

CD4 independence of simian immunodeficiency virus Envs is associated with macrophage tropism, neutralization sensitivity, and attenuated pathogenicity.

Puffer BA, Pöhlmann S, Edinger AL, Carlin D, Sanchez MD, Reitter J, Watry DD, Fox HS, Desrosiers RC, Doms RW.

J Virol. 2002 Mar;76(6):2595-605. PMID: 11861825

 

Antigen-presenting cells control T cell proliferation by regulating amino acid availability.

Edinger AL, Thompson CB.

Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1107-9. Review. No abstract available. PMID: 11830651

 

Akt and Bcl-xL promote growth factor-independent survival through distinct effects on mitochondrial physiology.

Plas DR, Talapatra S, Edinger AL, Rathmell JC, Thompson CB.

J Biol Chem. 2001 Apr 13;276(15):12041-8. Epub 2001 Jan 12. PMID: 11278698

 

Characterization and epitope mapping of neutralizing monoclonal antibodies produced by immunization with oligomeric simian immunodeficiency virus envelope protein.

Edinger AL, Ahuja M, Sung T, Baxter KC, Haggarty B, Doms RW, Hoxie JA.

J Virol. 2000 Sep;74(17):7922-35. PMID: 10933700

 

Chemokine and orphan receptors in HIV-2 and SIV tropism and pathogenesis.

Edinger AL, Clements JE, Doms RW.

Virology. 1999 Aug 1;260(2):211-21. Review. No abstract available. PMID: 10417256

 

Functional dissection of CCR5 coreceptor function through the use of CD4-independent simian immunodeficiency virus strains.

Edinger AL, Blanpain C, Kunstman KJ, Wolinsky SM, Parmentier M, Doms RW.

J Virol. 1999 May;73(5):4062-73. PMID: 10196302

 

Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse and human leukotriene B4 receptor-transfected cells.

Martin V, Ronde P, Unett D, Wong A, Hoffman TL, Edinger AL, Doms RW, Funk CD.

J Biol Chem. 1999 Mar 26;274(13):8597-603. PMID: 10085095

 

A Cell-Cell Fusion Assay to Monitor HIV-1 Env Interactions with Chemokine Receptors.

Edinger AL, Doms RW.

Methods Mol Med. 1999;17:41-9. doi: 10.1385/0-89603-369-4:41. PMID: 21380656

 

Use of GPR1, GPR15, and STRL33 as coreceptors by diverse human immunodeficiency virus type 1 and simian immunodeficiency virus envelope proteins.

Edinger AL, Hoffman TL, Sharron M, Lee B, O’Dowd B, Doms RW.

Virology. 1998 Sep 30;249(2):367-78. PMID: 9791028

 

An orphan seven-transmembrane domain receptor expressed widely in the brain functions as a coreceptor for human immunodeficiency virus type 1 and simian immunodeficiency virus.

Edinger AL, Hoffman TL, Sharron M, Lee B, Yi Y, Choe W, Kolson DL, Mitrovic B, Zhou Y, Faulds D, Collman RG, Hesselgesser J, Horuk R, Doms RW.

J Virol. 1998 Oct;72(10):7934-40. PMID: 9733831

 

ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-1 strains.

Samson M, Edinger AL, Stordeur P, Rucker J, Verhasselt V, Sharron M, Govaerts C, Mollereau C, Vassart G, Doms RW, Parmentier M.

Eur J Immunol. 1998 May;28(5):1689-700. PMID: 9603476

 

CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain.

Edinger AL, Mankowski JL, Doranz BJ, Margulies BJ, Lee B, Rucker J, Sharron M, Hoffman TL, Berson JF, Zink MC, Hirsch VM, Clements JE, Doms RW.

Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14742-7. PMID: 9405683

 

Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodeficiency viruses.

Rucker J, Edinger AL, Sharron M, Samson M, Lee B, Berson JF, Yi Y, Margulies B, Collman RG, Doranz BJ, Parmentier M, Doms RW.

J Virol. 1997 Dec;71(12):8999-9007. PMID: 9371556

 

Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains.

Edinger AL, Amedee A, Miller K, Doranz BJ, Endres M, Sharron M, Samson M, Lu ZH, Clements JE, Murphey-Corb M, Peiper SC, Parmentier M, Broder CC, Doms RW.

Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4005-10. PMID: 9108095

 

Cell-cell fusion assay to study role of chemokine receptors in human immunodeficiency virus type 1 entry.

Rucker J, Doranz BJ, Edinger AL, Long D, Berson JF, Doms RW.

Methods Enzymol. 1997;288:118-33. No abstract available. PMID: 9356991

Rab7 activation by growth factor withdrawal contributes to the induction of apoptosis.

Romero Rosales K, Peralta ER, Guenther GG, Wong SY, Edinger AL.

Mol Biol Cell. 2009 Jun;20(12):2831-40. doi: 10.1091/mbc.E08-09-0911. Epub 2009 Apr 22. PMID: 19386765

 

A new take on ceramide: starving cells by cutting off the nutrient supply.

Guenther GG, Edinger AL.

Cell Cycle. 2009 Apr 15;8(8):1122-6. Epub 2009 Apr 13. PMID: 19282666

 

Ceramide-induced starvation triggers homeostatic autophagy.

Peralta ER, Edinger AL.

Autophagy. 2009 Apr;5(3):407-9. Epub 2009 Apr 9. PMID: 19202357

 

Starvation in the midst of plenty: making sense of ceramide-induced autophagy by analysing nutrient transporter expression.

Edinger AL.

Biochem Soc Trans. 2009 Feb;37(Pt 1):253-8. doi: 10.1042/BST0370253. Review. PMID: 19143642

 

Ceramide starves cells to death by downregulating nutrient transporter proteins.

Guenther GG, Peralta ER, Rosales KR, Wong SY, Siskind LJ, Edinger AL.

Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17402-7. doi: 10.1073/pnas.0802781105. Epub 2008 Nov 3. PMID: 18981422

 

Higlighted in:

 

Cancer therapy: staying current with AMPK.

Fruman DA, Edinger AL.

Biochem J. 2008 Jun 1;412(2):e3-5. doi: 10.1042/BJ20080823. PMID: 18466113

 

Controlling cell growth and survival through regulated nutrient transporter expression.

Edinger AL.

Biochem J. 2007 Aug 15;406(1):1-12. Review. PMID: 17645414

 

Growth factors regulate cell survival by controlling nutrient transporter expression.

Edinger AL.

Biochem Soc Trans. 2005 Feb;33(Pt 1):225-7. Review. PMID: 15667313