Research Summary

Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays important roles in development, vascular biology, immune cell trafficking, carcinogenesis and other physiological processes. S1P mediates its actions primarily by signaling through a family of G protein-coupled receptors. Our research group is investigating the role of S1P metabolism and signaling in development and disease using cellular and animal models, translational approaches and metabolomics profiling. Our recent findings demonstrate that defects in S1P metabolism underlie a novel childhood syndrome called sphingosine phosphate lyase insufficiency syndrome (SPLIS), which is characterized by defects of kidney, adrenal gland, neurological system, skin and immune system. We are now developing several therapeutic approaches to the treatment of SPLIS including gene therapy and cofactor supplementation.

Research Funding

  • June 15, 2018 - May 31, 2022 - Endogenous and Dietary Sphingolipids as Modulators in Inflammatory Bowel Disease, Principal Investigator. Sponsor: NIH/NIDDK, Sponsor Award ID: R01DK115669
  • August 1, 2007 - June 30, 2015 - S1P Lyase in colon cancer, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA129438
  • June 1, 2014 - May 31, 2015 - Agilent 6490 Triple Quadrupole Mass Spectrometer, Principal Investigator. Sponsor: NIH, Sponsor Award ID: S10OD018070
  • June 15, 2013 - June 14, 2014 - IVIS Spectrum small animal imaging system, Principal Investigator. Sponsor: NIH, Sponsor Award ID: S10OD010335

Education

The Johns Hopkins University, MD, B.S., 05/1981, Natural Sciences
University of Maryland, School of Medicine, MD, M.D., 05/1985, Medicine
The Johns Hopkins University, MD, M.A., 05/1986, Creative Writing
Duke University, NC, Ph.D., 05/1996, Cell Biology

Honors & Awards

  • 1997
    International Union of Biochemistry and Molecular Biology Satellite Symposium on Sphingoglycolipids as Mediators of Molecular Events: Young Investigator Award
  • 2012
    John and Edna Beck Chair in Pediatric Cancer Research
  • 2014
    Women's History Month Trailblazer in STEM, Alameda County
  • 2014
    STEM Woman of the Year, CA Assembly District 15
  • 2014
    Swim Across America National Pediatric Research Laboratory
  • 2016
    CHORI Lifetime Scientific Achievement Award

Selected Publications

  1. Saba JD, Keller N, Wang JY, Tang F, Slavin A, Shen Y. Genotype/Phenotype Interactions and First Steps Toward Targeted Therapy for Sphingosine Phosphate Lyase Insufficiency Syndrome. Cell Biochem Biophys. 2021 Jun 16.  View on PubMed
  2. Zhao P, Tassew GB, Lee JY, Oskouian B, Muñoz DP, Hodgin JB, Watson GL, Tang F, Wang JY, Luo J, Yang Y, King S, Krauss RM, Keller N, Saba JD. Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome. JCI Insight. 2021 Apr 22; 6(8).  View on PubMed
  3. Martin KW, Weaver N, Alhasan K, Gumus E, Sullivan BR, Zenker M, Hildebrandt F, Saba JD. MRI Spectrum of Brain Involvement in Sphingosine-1-Phosphate Lyase Insufficiency Syndrome. AJNR Am J Neuroradiol. 2020 10; 41(10):1943-1948.  View on PubMed
  4. Zhao P, Liu ID, Hodgin JB, Benke PI, Selva J, Torta F, Wenk MR, Endrizzi JA, West O, Ou W, Tang E, Goh DL, Tay SK, Yap HK, Loh A, Weaver N, Sullivan B, Larson A, Cooper MA, Alhasan K, Alangari AA, Salim S, Gumus E, Chen K, Zenker M, Hildebrandt F, Saba JD. Responsiveness of sphingosine phosphate lyase insufficiency syndrome to vitamin B6 cofactor supplementation. J Inherit Metab Dis. 2020 09; 43(5):1131-1142.  View on PubMed
  5. Zhao P, Aguilar AE, Lee JY, Paul LA, Suh JH, Puri L, Zhang M, Beckstead J, Witkowski A, Ryan RO, Saba JD. Correction to: Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway. Invest New Drugs. 2019 Dec; 37(6):1309.  View on PubMed
  6. Durand D, Turati J, Rudi MJ, Ramírez D, Saba J, Caruso C, Carniglia L, von Bernhardi R, Lasaga M. Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor. Neurochem Int. 2019 12; 131:104547.  View on PubMed
  7. Saba JD. Fifty years of lyase and a moment of truth: sphingosine phosphate lyase from discovery to disease. J Lipid Res. 2019 03; 60(3):456-463.  View on PubMed
  8. Choi YJ, Saba JD. Sphingosine phosphate lyase insufficiency syndrome (SPLIS): A novel inborn error of sphingolipid metabolism. Adv Biol Regul. 2019 01; 71:128-140.  View on PubMed
  9. Saba J, Turati J, Ramírez D, Carniglia L, Durand D, Lasaga M, Caruso C. Astrocyte truncated tropomyosin receptor kinase B mediates brain-derived neurotrophic factor anti-apoptotic effect leading to neuroprotection. J Neurochem. 2018 09; 146(6):686-702.  View on PubMed
  10. Suh JH, Degagné É, Gleghorn EE, Setty M, Rodriguez A, Park KT, Verstraete SG, Heyman MB, Patel AS, Irek M, Gildengorin GL, Hubbard NE, Borowsky AD, Saba JD. Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study. Inflamm Bowel Dis. 2018 05 18; 24(6):1321-1334.  View on PubMed
  11. Zhao P, Aguilar AE, Lee JY, Paul LA, Suh JH, Puri L, Zhang M, Beckstead J, Witkowski A, Ryan RO, Saba JD. Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway. Invest New Drugs. 2018 10; 36(5):743-754.  View on PubMed
  12. Brian R. Dempsey, Anne C. Rintala-Dempsey, Gary S. Shaw, Igor Prudovsky, Thallapuranam Krishnaswamy Suresh Kumar, Rosario Donato, Rosario Donato, Guglielmo Sorci, Ileana Giambanco, Isadora Carolina Betim Pavan, Fernando Riback Silva, Ana Paula Morelli, Fernando Moreira Simabuco, Yuan Xiao Zhu, A. Keith Stewart, Jaime O. Claudio, Constance E. Runyan, H. William Schnaper, Sushant Singh, Sanjaya K. Sahoo, Muthu Periasamy, Erno Zádor, Magdolna Kósa, Chiung-Ya Chen, Yi-Ping Hsueh, Herman E. Popeijus, Alice Guyon, Laurence J. Miller, Sari S. Hannila, Manoj B. Menon, Akio Yamashita, Veerle Janssens, Ralf-Peter Czekay, Tessa M. Simone, Paul J. Higgins, David Della-Morte, Donatella Pastore, Barbara Capuani, Francesca Pacifici, Davide Lauro, Béatrice L. Charreau, Philip D. King, Matthew D. Blunt, Stephen G. Ward, Christophe Erneux, Stéphane Schurmans, Colin G. Rousseaux, Yasuyuki Saito, Yoji Murata, Takenori Kotani, Takashi Matozaki, Pedro Gomes, Xiaogang Chu, Ryan George, Raghavan Raju, Annegret Reinhold, Burkhart L. Schraven, Víctor Sorribas, Ali H. Jalloul, Robert T. Szerencsei, Tatiana P. Rogasevskaia, Paul P. M. Schnetkamp, Sylvia Y. M. Yao, James D. Young, Bruno Gasnier, Ian Forster, Andreas Werner, Laura R. de La Ballina, Tomás de Garay, Chloé C. Féral, Manuel Palacín, Meytal Landau, Mitsunori Fukuda, Jong Ran Lee, Salman Tamaddon-Jahromi, Venkateswarlu Kanamarlapudi, Julia Strebovsky, Jana Zimmer, Alexander H. Dalpke, Barbara Mariniello, Kaitlyn Ryan, Chin Chiang, Gianni Colotti, Andrea Ilari, Koji Shimozaki, Shiro Koizume, Yohei Miyagi, Aleksander Czogalla, Nadine Beckmann, Erich Gulbins, Katrin Anne Becker, Alexander Carpinteiro, Heidi Neubauer, Stuart Pitson, Ashok Kumar, Julie D. Saba, Samar Masoumi-Moghaddam, Afshin Amini, Sausan A. Moharram, Lars Rönnstrand, Julhash U. Kazi, Sausan A. Moharram, Lars Rönnstrand, Julhash U. Kazi, David A. Jans, Gurpreet Kaur, Cecilia Poderoso, Ana F. Castillo, Pablo G. Mele, Paula M. Maloberti, Ernesto J. Podestá, Su Jun Lim, Willis X. Li, Benjamin Skalkoyannis, Venkateswarlu Kanamarlapudi, Marc J. Tetel, Pui Man Rosalind Lai, Pradeep Kurup, Jian Xu, Manavi Chatterjee, Susan Goebel-Goody, Surojit Paul, Paul Lombroso, Wesley H. Brooks, Sreya Mukherjee, Malgorzata Kloc, Jacek Z. Kubiak, Pia Ragno, Jie Zhang, Zhi-wei Ye, Robert R. Bowers, Danyelle M. Townsend, Kenneth D. Tew, Mikko O. Laukkanen, Alessia Parascandolo, Niharika Swain, Rashmi Maruti Hosalkar, Payel Sen, Nilanjana Chatterjee, Blaine Bartholomew, Robert L. Geahlen, Ashley Bernardo, Shreya Prashar, Luke Molinaro, Ram Mishra, Sang-Ho Song, George J. Augustine, Niharika Swain, Rashmi Maruti Hosalkar, Samapika Routray, Valérie Drouet, Suzanne Lesage, Alexis Brice, Arie Horowitz. S100 Calcium Binding Protein A6. . 2018 Jan 1; 4793-4793.  View on PubMed
  13. Ashok Kumar, Julie D. Saba. Sphingosine-1-Phosphate. Encyclopedia of Signaling Molecules. 2018 Jan 1; 5128-5137.  View on PubMed
  14. Saba JD. The low down on sphingosine-1-phosphate lyase as a regulator of thymic egress. J Immunol Sci. 2017; 1(1):1-8.  View on PubMed
  15. Kumar A, Zamora-Pineda J, Degagné E, Saba JD. S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling. Mediators Inflamm. 2017; 2017:7685142.  View on PubMed
  16. Hahn C, Tyka K, Saba JD, Lenzen S, Gurgul-Convey E. Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity. J Biol Chem. 2017 12 08; 292(49):20292-20304.  View on PubMed
  17. Suh JH, Makarova AM, Gomez JM, Paul LA, Saba JD. An LC/MS/MS method for quantitation of chemopreventive sphingadienes in food products and biological samples. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Sep 01; 1061-1062:292-299.  View on PubMed
  18. Mitroi DN, Karunakaran I, Gräler M, Saba JD, Ehninger D, Ledesma MD, van Echten-Deckert G. SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production. Autophagy. 2017 May 04; 13(5):885-899.  View on PubMed
  19. Saba J, Logan AC. Obinutuzumab-induced serum sickness following salvage therapy for chronic lymphocytic leukemia. Clin Case Rep. 2017 06; 5(6):891-893.  View on PubMed
  20. Lovric S, Goncalves S, Gee HY, Oskouian B, Srinivas H, Choi WI, Shril S, Ashraf S, Tan W, Rao J, Airik M, Schapiro D, Braun DA, Sadowski CE, Widmeier E, Jobst-Schwan T, Schmidt JM, Girik V, Capitani G, Suh JH, Lachaussée N, Arrondel C, Patat J, Gribouval O, Furlano M, Boyer O, Schmitt A, Vuiblet V, Hashmi S, Wilcken R, Bernier FP, Innes AM, Parboosingh JS, Lamont RE, Midgley JP, Wright N, Majewski J, Zenker M, Schaefer F, Kuss N, Greil J, Giese T, Schwarz K, Catheline V, Schanze D, Franke I, Sznajer Y, Truant AS, Adams B, Désir J, Biemann R, Pei Y, Ars E, Lloberas N, Madrid A, Dharnidharka VR, Connolly AM, Willing MC, Cooper MA, Lifton RP, Simons M, Riezman H, Antignac C, Saba JD, Hildebrandt F. Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. J Clin Invest. 2017 Mar 01; 127(3):912-928.  View on PubMed

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