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The ToTOL research group combines the unique expertises Drs. Levi Beverly and Leah Siskind to study basic cancer biology, sphingolipid metabolism, experimental therapeutics, animal models and treatment-induced adverse side-effects.

The lab currently has projects focused on lung cancer, acute myeloid leukemia (AML), acute kidney disease and it progression to chronic kidney disease, as well as studies linking cancer and neurodegenerative conditions.

Ongoing Projects and Studies

Ubiquilin proteins in cancer and neurodegeneration

• Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells
  Kurlawala Z, Saurabh K, Dunaway R, Shah PP, Siskind LJ, Beverly LJ. J Cell Biochem. 2020 Jul 28. doi: 10.1002/jcb.29830. Online ahead of print. PMID: 32720736
• Regulation of insulin-like growth factor receptors by Ubiquilin1
  Kurlawala Z, Dunaway R, Shah PP, Gosney JA, Siskind LJ, Ceresa BP, Beverly LJ. Biochem J. 2017 Dec 6;474(24):4105-4118. doi: 10.1042/BCJ20170620. PMID: 29054976 Free PMC Article
• MIR155 Regulation of Ubiquilin1 and Ubiquilin2: Implications in Cellular Protection and Tumorigenesis
  Yadav S, Singh N, Shah PP, Rowbotham DA, Malik D, Srivastav A, Shankar J, Lam WL, Lockwood WW, Beverly LJ. Neoplasia. 2017 Apr;19(4):321-332. doi: 10.1016/j.neo.2017.02.001. Epub 2017 Mar 16. PMID: 28315615 Free PMC Article
• The STI and UBA Domains of UBQLN1 Are Critical Determinants of Substrate Interaction and Proteostasis
  Kurlawala Z, Shah PP, Shah C, Beverly LJ. J Cell Biochem. 2017 Aug;118(8):2261-2270. doi: 10.1002/jcb.25880. Epub 2017 Apr 25. PMID: 28075048 Free PMC Article
• Ubiquilin1 represses migration and epithelial-to-mesenchymal transition of human non-small cell lung cancer cells
  Shah PP, Lockwood WW, Saurabh K, Kurlawala Z, Shannon SP, Waigel S, Zacharias W, Beverly LJ. Oncogene. 2015 Mar 26;34(13):1709-17. doi: 10.1038/onc.2014.97. Epub 2014 Apr 21. PMID: 24747970 Free PMC Article

Cisplatin-induced acute to chronic kidney disease

• Loss of the Na+/H+ Exchange Regulatory Factor 1 Increases Susceptibility to Cisplatin-Induced Acute Kidney Injury
  Bushau-Sprinkle A, Barati M, Conklin C, Dupre T, Gagnon KB, Khundmiri SJ, Clark B, Siskind L, Doll MA, Rane M, Brier M, Coventry S, Lederer ED. Am J Pathol. 2019 Jun;189(6):1190-1200. doi: 10.1016/j.ajpath.2019.02.010. Epub 2019 Mar 27. PMID: 30926337
• Moderate aging does not exacerbate cisplatin-induced kidney injury or fibrosis despite altered inflammatory cytokine expression and immune cell infiltration
  Sharp CN, Doll M, Dupre TV, Beverly LJ, Siskind LJ. Am J Physiol Renal Physiol. 2019 Jan 1;316(1):F162-F172. doi: 10.1152/ajprenal.00463.2018. Epub 2018 Nov 28. PMID: 3048434
• The role of sphingolipids in acute kidney injury
  Dupre TV, Siskind LJ. Adv Biol Regul. 2018 Dec;70:31-39. doi: 10.1016/j.jbior.2018.11.003. Epub 2018 Nov 13. Review. PMID: 30455062
• Subclinical kidney injury induced by repeated cisplatin administration results in progressive chronic kidney disease
  Sharp CN, Doll MA, Megyesi J, Oropilla GB, Beverly LJ, Siskind LJ. Am J Physiol Renal Physiol. 2018 Jul 1;315(1):F161-F172. doi: 10.1152/ajprenal.00636.2017. Epub 2018 Jan 31. PMID: 29384415 Free PMC Article
• Developing better mouse models to study cisplatin-induced kidney injury
  Sharp CN, Siskind LJ.Am J Physiol Renal Physiol. 2017 Oct 1;313(4):F835-F841. doi: 10.1152/ajprenal.00285.2017. Epub 2017 Jul 19. Review. PMID: 28724610 Free PMC Article
• Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury
  Dupre TV, Doll MA, Shah PP, Sharp CN, Siow D, Megyesi J, Shayman J, Bielawska A, Bielawski J, Beverly LJ, Hernandez-Corbacho M, Clarke CJ, Snider AJ, Schnellmann RG, Obeid LM, Hannun YA, Siskind LJ. J Lipid Res. 2017 Jul;58(7):1439-1452. doi: 10.1194/jlr.M076745. Epub 2017 May 10. PMID: 28490444 Free PMC Article
• Bridging translation for acute kidney injury with better preclinical modeling of human disease
  Skrypnyk NI, Siskind LJ, Faubel S, de Caestecker MP. Am J Physiol Renal Physiol. 2016 May 15;310(10):F972-84. doi: 10.1152/ajprenal.00552.2015. Epub 2016 Mar 9. Review. PMID: 26962107 Free PMC Article
• Repeated administration of low-dose cisplatin in mice induces fibrosis
  Sharp CN, Doll MA, Dupre TV, Shah PP, Subathra M, Siow D, Arteel GE, Megyesi J, Beverly LJ, Siskind LJ. Am J Physiol Renal Physiol. 2016 Mar 15;310(6):F560-8. doi: 10.1152/ajprenal.00512.2015. Epub 2016 Jan 6. PMID: 26739893 Free PMC Article
• Suramin protects from cisplatin-induced acute kidney injury
  Dupre TV, Doll MA, Shah PP, Sharp CN, Kiefer A, Scherzer MT, Saurabh K, Saforo D, Siow D, Casson L, Arteel GE, Jenson AB, Megyesi J, Schnellmann RG, Beverly LJ, Siskind LJ. Am J Physiol Renal Physiol. 2016 Feb 1;310(3):F248-58. doi: 10.1152/ajprenal.00433.2015. Epub 2015 Dec 9. PMID: 26661653 Free PMC Article
• Kidney glycosphingolipids are elevated early in diabetic nephropathy and mediate hypertrophy of mesangial cells
  Subathra M, Korrapati M, Howell LA, Arthur JM, Shayman JA, Schnellmann RG, Siskind LJ. Am J Physiol Renal Physiol. 2015 Aug 1;309(3):F204-15. doi: 10.1152/ajprenal.00150.2015. Epub 2015 Jun 3. PMID: 26041445 Free PMC Article

Cancer cell-ECM interactions in metastasis

• Computational/experimental evaluation of liver metastasis post hepatic injury: interactions with macrophages and transitional ECM
  Hudson SV, Miller HA, Mahlbacher GE, Saforo D, Beverly LJ, Arteel GE, Frieboes HB. Sci Rep. 2019 Oct 21;9(1):15077. doi: 10.1038/s41598-019-51249-y. PMID: 31636296
• Primary lung cancer samples cultured under microenvironment-mimetic conditions enrich for mesenchymal stem-like cells that promote metastasis
  Saforo D, Omer L, Smolenkov A, Barve A, Casson L, Boyd N, Clark G, Siskind L, Beverly L. Sci Rep. 2019 Mar 12;9(1):4177. doi: 10.1038/s41598-019-40519-4. PMID: 30862796 Free PMC Article
• Fibroblast-Derived Extracellular Matrices: An Alternative Cell Culture System That Increases Metastatic Cellular Properties.
  Scherzer MT, Waigel S, Donninger H, Arumugam V, Zacharias W, Clark G, Siskind LJ, Soucy P, Beverly L. PLoS One. 2015 Sep 15;10(9):e0138065. doi: 10.1371/journal.pone.0138065. eCollection 2015. PMID: 26371754 Free PMC Article

Methionine and SAMe are crucial for AML survival

• Perturbation of Methionine/S-adenosylmethionine Metabolism as a Novel Vulnerability in MLL Rearranged Leukemia
  Barve A, Vega A, Shah PP, Ghare S, Casson L, Wunderlich M, Siskind LJ, Beverly LJ. Cells. 2019 Oct 25;8(11):1322. doi: 10.3390/cells8111322. PMID: 31717699