Julie Saba, MD, PhD

physician-scientist
(she/her/hers)

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.
Education
10/2020 - Diversity, Equity, and Inclusion Champion Training, University of California
Ph.D., 05/1996 - Biochemistry/Cell Biology, Duke University
Pediatric Fellowship, 07/1993 - Hematology/Oncology, Duke University Medical Center
Residency, 07/1989 - Pediatrics, Duke University Medical Center
M.A., 05/1986 - Creative Writing, Johns Hopkins University
M.D., 05/1985 - Medicine, University of Maryland School of Medicine
B.S., 05/1981 - Natural Sciences, Johns Hopkins University
Honors and Awards
  • Director, Swim Across America National Laboratory, Children's Hospital and Research Center Oakland, 2015
  • John and Edna Beck Chair in Pediatric Cancer Research, Children's Hospital and Research Center Oakland, 2012
Publications
  1. Analyzing Opposing Interactions Between Sphingosine 1-Phosphate Lyase and Influenza A Virus.
  2. Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile.
  3. Genotype/Phenotype Interactions and First Steps Toward Targeted Therapy for Sphingosine Phosphate Lyase Insufficiency Syndrome.
  4. Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome.
  5. MRI Spectrum of Brain Involvement in Sphingosine-1-Phosphate Lyase Insufficiency Syndrome.
  6. Responsiveness of sphingosine phosphate lyase insufficiency syndrome to vitamin B6 cofactor supplementation.
  7. Correction to: Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway.
  8. Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor.
  9. Fifty years of lyase and a moment of truth: sphingosine phosphate lyase from discovery to disease.
  10. Sphingosine phosphate lyase insufficiency syndrome (SPLIS): A novel inborn error of sphingolipid metabolism.
  11. Astrocyte truncated tropomyosin receptor kinase B mediates brain-derived neurotrophic factor anti-apoptotic effect leading to neuroprotection.
  12. Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study.
  13. Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway.
  14. S100 Calcium Binding Protein A6.
  15. Sphingosine-1-Phosphate.
  16. The low down on sphingosine-1-phosphate lyase as a regulator of thymic egress.
  17. S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.
  18. Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity.
  19. An LC/MS/MS method for quantitation of chemopreventive sphingadienes in food products and biological samples.
  20. SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production.
  21. Obinutuzumab-induced serum sickness following salvage therapy for chronic lymphocytic leukemia.
  22. Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency.
  23. Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases.
  24. Sphingosine 1-phosphate lyase ablation disrupts presynaptic architecture and function via an ubiquitin- proteasome mediated mechanism.
  25. Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress.
  26. Sphingosine-1-Phosphate.
  27. Regulation of Immune Cell Migration by Sphingosine-1-Phosphate.
  28. Sphingosine-1-phosphate in inflammatory bowel disease and colitis-associated colon cancer: the fat's in the fire.
  29. A facile stable-isotope dilution method for determination of sphingosine phosphate lyase activity.
  30. A B cell-dependent mechanism restrains T cell transendothelial migration.
  31. Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs.
  32. Tracking hippo in the cancer jungle.
  33. S1pping fire: Sphingosine-1-phosphate signaling as an emerging target in inflammatory bowel disease and colitis-associated cancer.
  34. Sphingosine phosphate lyase regulates myogenic differentiation via S1P receptor-mediated effects on myogenic microRNA expression.
  35. Sphingosine Phosphate Lyase Regulates Murine Embryonic Stem Cell Proliferation and Pluripotency through an S1P2/STAT3 Signaling Pathway.
  36. A novel role of a lipid species, sphingosine-1-phosphate, in epithelial innate immunity.
  37. Immunohistochemical analysis of sphingosine phosphate lyase expression during murine development.
  38. Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues.
  39. S1P lyase in skeletal muscle regeneration and satellite cell activation: exposing the hidden lyase.
  40. The sphingolipid degradation product trans-2-hexadecenal forms adducts with DNA.
  41. Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.
  42. Chemopreventive sphingadienes downregulate Wnt signaling via a PP2A/Akt/GSK3β pathway in colon cancer.
  43. Corrigendum to “The sphingolipid degradation product trans-2-hexadecenal induces cytoskeletal reorganization and apoptosis in a JNK-dependent manner” [Cell. Signal. 23(7) (2011) 1144-1152].
  44. S100 Calcium-Binding Protein.
  45. Sphingosine-1-Phosphate.
  46. Truth and consequences of sphingosine-1-phosphate lyase.
  47. A suppressor/enhancer screen in Drosophila reveals a role for wnt-mediated lipid metabolism in primordial germ cell migration.
  48. Sphingolipid signaling and hematopoietic malignancies: to the rheostat and beyond.
  49. A monoclonal antibody to O-acetyl-GD2 ganglioside and not to GD2 shows potent anti-tumor activity without peripheral nervous system cross-reactivity.
  50. S1P lyase regulates DNA damage responses in vitro and in vivo.
  51. The sphingolipid degradation product trans-2-hexadecenal induces cytoskeletal reorganization and apoptosis in a JNK-dependent manner.
  52. S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart.
  53. S1P lyase regulates DNA damage responses through a novel sphingolipid feedback mechanism.
  54. Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response while impairing neutrophil trafficking.
  55. Protection of LPS-induced murine acute lung injury by sphingosine-1-phosphate lyase suppression.
  56. Erratum: An update on sphingosine-1-phosphate and other sphingolipid mediators.
  57. An update on sphingosine-1-phosphate and other sphingolipid mediators.
  58. S1P metabolism in cancer and other pathological conditions.
  59. Synopsis of partial-body radiation diagnostic biomarkers and medical management of radiation injury workshop.
  60. Sphingosine 1-phosphate lyase deficiency disrupts lipid homeostasis in liver.
  61. Cancer treatment strategies targeting sphingolipid metabolism.
  62. Natural sphingadienes inhibit Akt-dependent signaling and prevent intestinal tumorigenesis.
  63. Sphingosine 1-phosphate lyase, a key regulator of sphingosine 1-phosphate signaling and function.
  64. Normalization of diabetic wound healing.
  65. Lyase to live by: sphingosine phosphate lyase as a therapeutic target.
  66. Sphingosine 1-phosphate lyase enzyme assay using a BODIPY-labeled substrate.
  67. Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cells.
  68. Sphingosine-1-phosphate lyase in development and disease: sphingolipid metabolism takes flight.
  69. Identification and characterization by electrospray mass spectrometry of endogenous Drosophila sphingadienes.
  70. A rapid fluorescence assay for sphingosine-1-phosphate lyase enzyme activity.
  71. Disruption of sphingolipid metabolism elicits apoptosis-associated reproductive defects in Drosophila.
  72. Sphingosine-1-phosphate lyase in immunity and cancer: silencing the siren.
  73. Sphingosine-1-phosphate metabolism and intestinal tumorigenesis: lipid signaling strikes again.
  74. Redirection of sphingolipid metabolism toward de novo synthesis of ethanolamine in Leishmania.
  75. Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer.
  76. Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation.
  77. S1P Lyase Expression Hypersensitizes Cells to DNA Damage and Other Stress Conditions via p53 and p38 Apoptosis Pathways.
  78. Sphingosine 1-phosphate/sphingosine 1-phosphate receptor 1 signaling in rheumatoid synovium: regulation of synovial proliferation and inflammatory gene expression.
  79. Sphingosine-1-Phosphate Lyase.
  80. Directed Donor Cord Blood Transplantation for Hematological Disorders.
  81. The immune modulator FTY720 inhibits sphingosine-1-phosphate lyase activity.
  82. Regulation of sphingosine-1-phosphate lyase gene expression by members of the GATA family of transcription factors.
  83. Sibling donor cord blood transplantation for thalassemia major: Experience of the Sibling Donor Cord Blood Program.
  84. gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis.
  85. Death and taxis: what non-mammalian models tell us about sphingosine-1-phosphate.
  86. Lysophospholipids in development: Miles apart and edging in.
  87. Point-counterpoint of sphingosine 1-phosphate metabolism.
  88. Characterization of the Drosophila sphingosine kinases and requirement for Sk2 in normal reproductive function.
  89. Sphingosine-phosphate lyase enhances stress-induced ceramide generation and apoptosis.
  90. Characterization of free endogenous C14 and C16 sphingoid bases from Drosophila melanogaster.
  91. Sply regulation of sphingolipid signaling molecules is essential for Drosophila development.
  92. Sphingosine phosphate lyase expression is essential for normal development in Caenorhabditis elegans.
  93. Comprehensive banking of sibling donor cord blood for children with malignant and nonmalignant disease.
  94. Calcium influx and signaling in yeast stimulated by intracellular sphingosine 1-phosphate accumulation.
  95. Accumulation of phosphorylated sphingoid long chain bases results in cell growth inhibition in Saccharomyces cerevisiae.
  96. Molecular cloning - and functional characterization of the human sphingosine-1 -phosphate lyase gene.
  97. A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples.
  98. The dihydrosphingosine-1-phosphate phosphatases of Saccharomyces cerevisiae are important regulators of cell proliferation and heat stress responses.
  99. The dihydrosphingosine-1-phosphate phosphatases of Saccharomyces cerevisiae are important regulators of cell proliferation and heat stress responses.
  100. The PLB2 gene of Saccharomyces cerevisiae confers resistance to lysophosphatidylcholine and encodes a phospholipase B/lysophospholipase.
  101. The DPL1 gene is involved in mediating the response to nutrient deprivation in Saccharomyces cerevisiae.
  102. YAP1 confers resistance to the fatty acid synthase inhibitor cerulenin through the transporter Flr1p in Saccharomyces cerevisiae.
  103. Characterization of sphingosine kinase (SK) activity in Saccharomyces cerevisiae and isolation of SK-deficient mutants.
  104. Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast.
  105. The BST1 gene of Saccharomyces cerevisiae is the sphingosine-1-phosphate lyase.
  106. Ceramide: an intracellular mediator of apoptosis and growth suppression.
  107. Ceramide-mediated growth inhibition and CAPP are conserved in Saccharomyces cerevisiae.
  108. A seven-month-old infant with fever and neutrophilic leukocytosis.
  109. Large-cell lymphoma presenting with a distinctive inflammatory dermatosis.
  110. Pelger-Huet anomaly in an infant with multiple congenital anomalies.
  111. A piece of my mind. The poetry of medicine.
  112. Catheter-related sepsis refractory to antibiotics treated successfully with adjunctive urokinase infusion.
  113. Indicator enzyme assays. II. Adenylate kinase: application to human muscle biopsies and blood cells.
  114. Journal of Immunological Sciences
  115. Sphingosine-1-phosphate signaling and metabolism gene signature in pediatric inflammatory bowel disease: a matched-case control pilot study