Dr. Timothy Hla's laboratory has been investigating the role of lipid mediators, sphingosine 1-phosphate (S1P) and prostanoids in vascular biology and disease. In the 1990s, we cloned the inducible cyclooxygenase (COX-2) and the first S1P receptor. Our work defined how the COX-2 pathway regulated angiogenesis, cancer and inflammatory disease. Recently, we are examining molecular mechanisms by which prostanoids interact with other lipid signaling systems to protect the vascular system and maintain health. Secondly, since our discovery of the S1P receptor we have been working on this novel signaling pathway to understand how it regulates vascular development and homeostasis and is dysregulated in vascular diseases. In addition, our work contributed to the development of S1P receptor inhibitors, which are being tested and used for treatment of a number of autoimmune diseases. Recently, we discovered that HDL-bound S1P activates vascular S1P receptors to inhibit vascular injury and disease. We also showed that proteins that bind to S1P, such as the HDL-bound apolipoprotein M (ApoM), direct specific biological functions of S1P by activating S1P receptors in unique ways. This mode of signaling, termed as, chaperone-dependent S1P signaling, may be a general mechanism for lipid mediators that are poorly soluble in water. We are also examining novel mechanisms of S1P metabolism, export into the extracellular environment, capture and signaling by novel chaperones, receptor-dependent signaling mechanisms and cross-talk with other cytokine, growth factor signaling pathways. Such mechanistic information is useful not only to achieve a deeper understanding of vascular health and disease but also to develop new therapeutic entities based on the S1P signaling system, In fact, our laboratory is developing novel small molecular as well as protein biotherapeutics with the potential to modulate diseases such as heart disease, stroke, autoimmune diseases, eye disease and cancer.

About the Researcher

Timothy Hla received his Ph.D. in biochemistry from The George Washington University. Following a post-doctoral training period in which he worked in the lab of Thomas Maciag, he started his laboratory at the Holland Laboratory at the American Red Cross, Rockville, MD. He was recruited to the University of Connecticut School of Medicine in Farmington, CT where he founded the research Center for Vascular Biology and was eventually promoted to Professor. In 2009, he was recruited as a Professor and Director of the Center for Vascular Biology at Weill Cornell Medicine, Cornell University. He moved his research program to Boston Children's Hospital in 2016 where he is appointed as an investigator at the Vascular Biology Program and Patricia K. Donohoe Professor of Surgery at the Harvard Medical School. Dr. Hla is an honorary member of the Japanese Biochemical Society, received an honorary M.D. degree from the Geothe University, Frankfurt, Germany and a MERIT award from the NHLBI, NIH in 2006.

For more information about current projects, please visit the Hla Lab Website.

Researcher Services

Researcher Areas

  • Lipid Mediators in Vascular Biology and Disease
  • Sphingosine 1 Phosphate Signaling
  • Gene Regulation in Vascular System

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Hisano Y, Hla T. Bioactive lysolipids in cancer and angiogenesis. Pharmacol Ther. 2018 Jul 23. View abstract
  2. Burg N, Swendeman S, Worgall S, Hla T, Salmon JE. Sphingosine -1 Phosphate Receptor-1 signaling maintains endothelial cell barrier function and protects against immune complex-induced vascular injury. Arthritis Rheumatol. 2018 May 21. View abstract
  3. Ghosh M, Thangada S, Dasgupta O, Khanna KM, Yamase HT, Kashgarian M, Hla T, Shapiro LH, Ferrer FA. Cell-intrinsic sphingosine kinase 2 promotes macrophage polarization and renal inflammation in response to unilateral ureteral obstruction. PLoS One. 2018; 13(3):e0194053. View abstract
  4. Yanagida K, Hla T. A dark side to omega-3 fatty acids. Nature. 2017 12 14; 552(7684):180-181. View abstract
  5. Kono M, Conlon EG, Lux SY, Yanagida K, Hla T, Proia RL. Bioluminescence imaging of G protein-coupled receptor activation in living mice. Nat Commun. 2017 Oct 27; 8(1):1163. View abstract
  6. Mendelson K, Pandey S, Hisano Y, Carellini F, Das B, Hla T, Evans T. The ceramide synthase 2b gene mediates genomic sensing and regulation of sphingosine levels during zebrafish embryogenesis. Elife. 2017 09 28; 6. View abstract
  7. Singh RK, Haka AS, Brumfield A, Grosheva I, Bhardwaj P, Chin HF, Xiong Y, Hla T, Maxfield FR. Ceramide activation of RhoA/Rho kinase impairs actin polymerization during aggregated LDL catabolism. J Lipid Res. 2017 Oct; 58(10):1977-1987. View abstract
  8. Swendeman SL, Xiong Y, Cantalupo A, Yuan H, Burg N, Hisano Y, Cartier A, Liu CH, Engelbrecht E, Blaho V, Zhang Y, Yanagida K, Galvani S, Obinata H, Salmon JE, Sanchez T, Di Lorenzo A, Hla T. An engineered S1P chaperone attenuates hypertension and ischemic injury. Sci Signal. 2017 Aug 15; 10(492). View abstract
  9. Etemadi N, Chopin M, Anderton H, Tanzer MC, Rickard JA, Abeysekera W, Hall C, Spall SK, Wang B, Xiong Y, Hla T, Pitson SM, Bonder CS, Wong WW, Ernst M, Smyth GK, Vaux DL, Nutt SL, Nachbur U, Silke J. Correction: TRAF2 regulates TNF and NF-?B signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1. Elife. 2017 06 27; 6. View abstract
  10. Cantalupo A, Gargiulo A, Dautaj E, Liu C, Zhang Y, Hla T, Di Lorenzo A. S1PR1 (Sphingosine-1-Phosphate Receptor 1) Signaling Regulates Blood Flow and Pressure. Hypertension. 2017 08; 70(2):426-434. View abstract
  11. Galvani S, Hla T. Quality Versus Quantity: Making HDL Great Again. Arterioscler Thromb Vasc Biol. 2017 Jun; 37(6):1018-1019. View abstract
  12. Mendoza A, Fang V, Chen C, Serasinghe M, Verma A, Muller J, Chaluvadi VS, Dustin ML, Hla T, Elemento O, Chipuk JE, Schwab SR. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells. Nature. 2017 06 01; 546(7656):158-161. View abstract
  13. Yanagida K, Liu CH, Faraco G, Galvani S, Smith HK, Burg N, Anrather J, Sanchez T, Iadecola C, Hla T. Size-selective opening of the blood-brain barrier by targeting endothelial sphingosine 1-phosphate receptor 1. Proc Natl Acad Sci U S A. 2017 04 25; 114(17):4531-4536. View abstract
  14. Ding BS, Liu CH, Sun Y, Chen Y, Swendeman SL, Jung B, Chavez D, Cao Z, Christoffersen C, Nielsen LB, Schwab SR, Rafii S, Hla T. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P1) promotes regeneration and suppresses fibrosis in the liver. JCI Insight. 2016 Dec 22; 1(21):e87058. View abstract
  15. Yanagida K, Hla T. Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient. Annu Rev Physiol. 2017 02 10; 79:67-91. View abstract
  16. Gazit SL, Mariko B, Thérond P, Decouture B, Xiong Y, Couty L, Bonnin P, Baudrie V, Le Gall SM, Dizier B, Zoghdani N, Ransinan J, Hamilton JR, Gaussem P, Tharaux PL, Chun J, Coughlin SR, Bachelot-Loza C, Hla T, Ho-Tin-Noé B, Camerer E. Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock. Circ Res. 2016 Sep 30; 119(8):e110-26. View abstract
  17. Xiong Y, Lee HJ, Mariko B, Lu YC, Dannenberg AJ, Haka AS, Maxfield FR, Camerer E, Proia RL, Hla T. Sphingosine kinases are not required for inflammatory responses in macrophages. J Biol Chem. 2016 May 20; 291(21):11465. View abstract
  18. Christensen PM, Liu CH, Swendeman SL, Obinata H, Qvortrup K, Nielsen LB, Hla T, Di Lorenzo A, Christoffersen C. Impaired endothelial barrier function in apolipoprotein M-deficient mice is dependent on sphingosine-1-phosphate receptor 1. FASEB J. 2016 06; 30(6):2351-9. View abstract
  19. Etemadi N, Chopin M, Anderton H, Tanzer MC, Rickard JA, Abeysekera W, Hall C, Spall SK, Wang B, Xiong Y, Hla T, Pitson SM, Bonder CS, Wong WW, Ernst M, Smyth GK, Vaux DL, Nutt SL, Nachbur U, Silke J. TRAF2 regulates TNF and NF-?B signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1. Elife. 2015 Dec 23; 4. View abstract
  20. Wagschal A, Najafi-Shoushtari SH, Wang L, Goedeke L, Sinha S, deLemos AS, Black JC, Ramírez CM, Li Y, Tewhey R, Hatoum I, Shah N, Lu Y, Kristo F, Psychogios N, Vrbanac V, Lu YC, Hla T, de Cabo R, Tsang JS, Schadt E, Sabeti PC, Kathiresan S, Cohen DE, Whetstine J, Chung RT, Fernández-Hernando C, Kaplan LM, Bernards A, Gerszten RE, Näär AM. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. Nat Med. 2015 Nov; 21(11):1290-7. View abstract
  21. Cantalupo A, Zhang Y, Kothiya M, Galvani S, Obinata H, Bucci M, Giordano FJ, Jiang XC, Hla T, Di Lorenzo A. Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure. Nat Med. 2015 Sep; 21(9):1028-1037. View abstract
  22. Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, Dahlbäck B, Kono M, Proia RL, Smith JD, Hla T. HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal. 2015 Aug 11; 8(389):ra79. View abstract
  23. Mendelson K, Lan Y, Hla T, Evans T. Maternal or zygotic sphingosine kinase is required to regulate zebrafish cardiogenesis. Dev Dyn. 2015 Aug; 244(8):948-54. View abstract
  24. Li MH, Swenson R, Harel M, Jana S, Stolarzewicz E, Hla T, Shapiro LH, Ferrer F. Antitumor Activity of a Novel Sphingosine-1-Phosphate 2 Antagonist, AB1, in Neuroblastoma. J Pharmacol Exp Ther. 2015 Sep; 354(3):261-8. View abstract
  25. Blaho VA, Galvani S, Engelbrecht E, Liu C, Swendeman SL, Kono M, Proia RL, Steinman L, Han MH, Hla T. HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature. 2015 Jul 16; 523(7560):342-6. View abstract
  26. Proia RL, Hla T. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015 Apr; 125(4):1379-87. View abstract
  27. Lu YC, Chang SH, Hafner M, Li X, Tuschl T, Elemento O, Hla T. ELAVL1 modulates transcriptome-wide miRNA binding in murine macrophages. Cell Rep. 2014 Dec 24; 9(6):2330-43. View abstract
  28. Chang SH, Elemento O, Zhang J, Zhuang ZW, Simons M, Hla T. ELAVL1 regulates alternative splicing of eIF4E transporter to promote postnatal angiogenesis. Proc Natl Acad Sci U S A. 2014 Dec 23; 111(51):18309-14. View abstract
  29. Hla T, Kolesnick R. C16:0-ceramide signals insulin resistance. Cell Metab. 2014 Nov 04; 20(5):703-705. View abstract
  30. Obinata H, Gutkind S, Stitham J, Okuno T, Yokomizo T, Hwa J, Hla T. Individual variation of human S1P1 coding sequence leads to heterogeneity in receptor function and drug interactions. J Lipid Res. 2014 Dec; 55(12):2665-75. View abstract
  31. Xiong Y, Yang P, Proia RL, Hla T. Erythrocyte-derived sphingosine 1-phosphate is essential for vascular development. J Clin Invest. 2014 Nov; 124(11):4823-8. View abstract
  32. Murakami K, Kohno M, Kadoya M, Nagahara H, Fujii W, Seno T, Yamamoto A, Oda R, Fujiwara H, Kubo T, Morita S, Nakada H, Hla T, Kawahito Y. Knock out of S1P3 receptor signaling attenuates inflammation and fibrosis in bleomycin-induced lung injury mice model. PLoS One. 2014; 9(9):e106792. View abstract
  33. Huang C, Gonzalez DG, Cote CM, Jiang Y, Hatzi K, Teater M, Dai K, Hla T, Haberman AM, Melnick A. The BCL6 RD2 domain governs commitment of activated B cells to form germinal centers. Cell Rep. 2014 Sep 11; 8(5):1497-508. View abstract
  34. Giammanco A, Blanc V, Montenegro G, Klos C, Xie Y, Kennedy S, Luo J, Chang SH, Hla T, Nalbantoglu I, Dharmarajan S, Davidson NO. Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development. Cancer Res. 2014 Sep 15; 74(18):5322-35. View abstract
  35. Camm J, Hla T, Bakshi R, Brinkmann V. Cardiac and vascular effects of fingolimod: mechanistic basis and clinical implications. Am Heart J. 2014 Nov; 168(5):632-44. View abstract
  36. Garris CS, Blaho VA, Hla T, Han MH. Sphingosine-1-phosphate receptor 1 signalling in T cells: trafficking and beyond. Immunology. 2014 Jul; 142(3):347-53. View abstract
  37. Li MH, Harel M, Hla T, Ferrer F. Induction of chemokine (C-C motif) ligand 2 by sphingosine-1-phosphate signaling in neuroblastoma. J Pediatr Surg. 2014 Aug; 49(8):1286-91. View abstract
  38. Chang SH, Hla T. Post-transcriptional gene regulation by HuR and microRNAs in angiogenesis. Curr Opin Hematol. 2014 May; 21(3):235-40. View abstract
  39. Thangada S, Shapiro LH, Silva C, Yamase H, Hla T, Ferrer FA. Treatment with the immunomodulator FTY720 (fingolimod) significantly reduces renal inflammation in murine unilateral ureteral obstruction. J Urol. 2014 May; 191(5 Suppl):1508-16. View abstract
  40. Blaho VA, Hla T. An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res. 2014 Aug; 55(8):1596-608. View abstract
  41. Li X, Lu YC, Dai K, Torregroza I, Hla T, Evans T. Elavl1a regulates zebrafish erythropoiesis via posttranscriptional control of gata1. Blood. 2014 Feb 27; 123(9):1384-92. View abstract
  42. Mendelson K, Evans T, Hla T. Sphingosine 1-phosphate signalling. Development. 2014 Jan; 141(1):5-9. View abstract
  43. Xiong Y, Hla T. S1P control of endothelial integrity. Curr Top Microbiol Immunol. 2014; 378:85-105. View abstract
  44. Xiong Y, Lee HJ, Mariko B, Lu YC, Dannenberg AJ, Haka AS, Maxfield FR, Camerer E, Proia RL, Hla T. Sphingosine kinases are not required for inflammatory responses in macrophages. J Biol Chem. 2013 Nov 08; 288(45):32563-73. View abstract
  45. Garris CS, Wu L, Acharya S, Arac A, Blaho VA, Huang Y, Moon BS, Axtell RC, Ho PP, Steinberg GK, Lewis DB, Sobel RA, Han DK, Steinman L, Snyder MP, Hla T, Han MH. Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation. Nat Immunol. 2013 Nov; 14(11):1166-72. View abstract
  46. Li MH, Hla T, Ferrer F. FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway. Pediatr Blood Cancer. 2013 Sep; 60(9):1418-23. View abstract
  47. Howe LR, Subbaramaiah K, Kent CV, Zhou XK, Chang SH, Hla T, Jakobsson PJ, Hudis CA, Dannenberg AJ. Genetic deletion of microsomal prostaglandin E synthase-1 suppresses mouse mammary tumor growth and angiogenesis. Prostaglandins Other Lipid Mediat. 2013 Oct; 106:99-105. View abstract
  48. Montrose DC, Scherl EJ, Bosworth BP, Zhou XK, Jung B, Dannenberg AJ, Hla T. S1P1 localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity. J Lipid Res. 2013 Mar; 54(3):843-51. View abstract
  49. Mendelson K, Zygmunt T, Torres-Vázquez J, Evans T, Hla T. Sphingosine 1-phosphate receptor signaling regulates proper embryonic vascular patterning. J Biol Chem. 2013 Jan 25; 288(4):2143-56. View abstract
  50. Chang SH, Lu YC, Li X, Hsieh WY, Xiong Y, Ghosh M, Evans T, Elemento O, Hla T. Antagonistic function of the RNA-binding protein HuR and miR-200b in post-transcriptional regulation of vascular endothelial growth factor-A expression and angiogenesis. J Biol Chem. 2013 Feb 15; 288(7):4908-21. View abstract
  51. Hla T, Galvani S, Rafii S, Nachman R. S1P and the birth of platelets. J Exp Med. 2012 Nov 19; 209(12):2137-40. View abstract
  52. Torregroza I, Holtzinger A, Mendelson K, Liu TC, Hla T, Evans T. Regulation of a vascular plexus by gata4 is mediated in zebrafish through the chemokine sdf1a. PLoS One. 2012; 7(10):e46844. View abstract
  53. Obinata H, Hla T. Fine-tuning S1P therapeutics. Chem Biol. 2012 Sep 21; 19(9):1080-2. View abstract
  54. Hla T, Dannenberg AJ. Sphingolipid signaling in metabolic disorders. Cell Metab. 2012 Oct 03; 16(4):420-34. View abstract
  55. Jung B, Obinata H, Galvani S, Mendelson K, Ding BS, Skoura A, Kinzel B, Brinkmann V, Rafii S, Evans T, Hla T. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev Cell. 2012 Sep 11; 23(3):600-10. View abstract
  56. Takeshita H, Kitano M, Iwasaki T, Kitano S, Tsunemi S, Sato C, Sekiguchi M, Azuma N, Miyazawa K, Hla T, Sano H. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-?B ligand (RANKL) expression in rheumatoid arthritis. Biochem Biophys Res Commun. 2012 Mar 09; 419(2):154-9. View abstract
  57. Moolenaar WH, Hla T. SnapShot: Bioactive lysophospholipids. Cell. 2012 Jan 20; 148(1-2):378-378.e2. View abstract
  58. Obinata H, Hla T. Assessment of sphingosine-1-phosphate activity in biological samples by receptor internalization and adherens junction formation. Methods Mol Biol. 2012; 874:69-76. View abstract
  59. Blaho VA, Hla T. Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors. Chem Rev. 2011 Oct 12; 111(10):6299-320. View abstract
  60. Obinata H, Hla T. Sphingosine 1-phosphate in coagulation and inflammation. Semin Immunopathol. 2012 Jan; 34(1):73-91. View abstract
  61. Chang SH, Hla T. Gene regulation by RNA binding proteins and microRNAs in angiogenesis. Trends Mol Med. 2011 Nov; 17(11):650-8. View abstract
  62. Christoffersen C, Obinata H, Kumaraswamy SB, Galvani S, Ahnström J, Sevvana M, Egerer-Sieber C, Muller YA, Hla T, Nielsen LB, Dahlbäck B. Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M. Proc Natl Acad Sci U S A. 2011 Jun 07; 108(23):9613-8. View abstract
  63. Li MH, Hla T, Ferrer F. Sphingolipid modulation of angiogenic factor expression in neuroblastoma. Cancer Prev Res (Phila). 2011 Aug; 4(8):1325-32. View abstract
  64. Oo ML, Chang SH, Thangada S, Wu MT, Rezaul K, Blaho V, Hwang SI, Han DK, Hla T. Engagement of S1P1-degradative mechanisms leads to vascular leak in mice. J Clin Invest. 2011 Jun; 121(6):2290-300. View abstract
  65. Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK, Zhou XK, Blaho VA, Hla T, Yang P, Kopelovich L, Hudis CA, Dannenberg AJ. Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res (Phila). 2011 Mar; 4(3):329-46. View abstract
  66. Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology. 2011 Feb 22; 76(8 Suppl 3):S3-8. View abstract
  67. Chun J, Hla T, Lynch KR, Spiegel S, Moolenaar WH. International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol Rev. 2010 Dec; 62(4):579-87. View abstract
  68. Skoura A, Michaud J, Im DS, Thangada S, Xiong Y, Smith JD, Hla T. Sphingosine-1-phosphate receptor-2 function in myeloid cells regulates vascular inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol. 2011 Jan; 31(1):81-5. View abstract
  69. Thangada S, Khanna KM, Blaho VA, Oo ML, Im DS, Guo C, Lefrancois L, Hla T. Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics. J Exp Med. 2010 Jul 05; 207(7):1475-83. View abstract
  70. Habrukowich C, Han DK, Le A, Rezaul K, Pan W, Ghosh M, Li Z, Dodge-Kafka K, Jiang X, Bittman R, Hla T. Sphingosine interaction with acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) regulates PP2A activity and cyclooxygenase (COX)-2 expression in human endothelial cells. J Biol Chem. 2010 Aug 27; 285(35):26825-31. View abstract
  71. Michaud J, Im DS, Hla T. Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment during inflammation. J Immunol. 2010 Feb 01; 184(3):1475-83. View abstract
  72. Hla T, Oo ML. Ramping up RANTES in the acute response to arterial injury. J Clin Invest. 2010 Jan; 120(1):90-2. View abstract
  73. Ghosh M, Aguila HL, Michaud J, Ai Y, Wu MT, Hemmes A, Ristimaki A, Guo C, Furneaux H, Hla T. Essential role of the RNA-binding protein HuR in progenitor cell survival in mice. J Clin Invest. 2009 Dec; 119(12):3530-43. View abstract
  74. Hla T. Plugging vascular leak by sphingosine kinase from bone marrow progenitor cells. Circ Res. 2009 Sep 25; 105(7):614-6. View abstract
  75. ter Braak M, Danneberg K, Lichte K, Liphardt K, Ktistakis NT, Pitson SM, Hla T, Jakobs KH, Meyer zu Heringdorf D. Galpha(q)-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors. Biochim Biophys Acta. 2009 May; 1791(5):357-70. View abstract
  76. Skoura A, Hla T. Regulation of vascular physiology and pathology by the S1P2 receptor subtype. Cardiovasc Res. 2009 May 01; 82(2):221-8. View abstract
  77. Hla T, Im DS. Cell biology. The ABCs of lipophile transport. Science. 2009 Feb 13; 323(5916):883-4. View abstract
  78. Li MH, Sanchez T, Milne GL, Morrow JD, Hla T, Ferrer F. S1P/S1P2 signaling induces cyclooxygenase-2 expression in Wilms tumor. J Urol. 2009 Mar; 181(3):1347-52. View abstract
  79. Li MH, Sanchez T, Yamase H, Hla T, Oo ML, Pappalardo A, Lynch KR, Lin CY, Ferrer F. S1P/S1P1 signaling stimulates cell migration and invasion in Wilms tumor. Cancer Lett. 2009 Apr 18; 276(2):171-9. View abstract
  80. Ghosh M, Ai Y, Narko K, Wang Z, Peters JM, Hla T. PPARdelta is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer. Prostaglandins Other Lipid Mediat. 2009 Apr; 88(3-4):97-100. View abstract
  81. Skoura A, Hla T. Lysophospholipid receptors in vertebrate development, physiology, and pathology. J Lipid Res. 2009 Apr; 50 Suppl:S293-8. View abstract
  82. Li MH, Sanchez T, Pappalardo A, Lynch KR, Hla T, Ferrer F. Induction of antiproliferative connective tissue growth factor expression in Wilms' tumor cells by sphingosine-1-phosphate receptor 2. Mol Cancer Res. 2008 Oct; 6(10):1649-56. View abstract
  83. Estrada R, Zeng Q, Lu H, Sarojini H, Lee JF, Mathis SP, Sanchez T, Wang E, Kontos CD, Lin CY, Hla T, Haribabu B, Lee MJ. Up-regulating sphingosine 1-phosphate receptor-2 signaling impairs chemotactic, wound-healing, and morphogenetic responses in senescent endothelial cells. J Biol Chem. 2008 Oct 31; 283(44):30363-75. View abstract
  84. Hla T, Venkataraman K, Michaud J. The vascular S1P gradient-cellular sources and biological significance. Biochim Biophys Acta. 2008 Sep; 1781(9):477-82. View abstract
  85. Venkataraman K, Lee YM, Michaud J, Thangada S, Ai Y, Bonkovsky HL, Parikh NS, Habrukowich C, Hla T. Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ Res. 2008 Mar 28; 102(6):669-76. View abstract
  86. Sekiguchi M, Iwasaki T, Kitano M, Kuno H, Hashimoto N, Kawahito Y, Azuma M, Hla T, Sano H. Role of sphingosine 1-phosphate in the pathogenesis of Sjögren's syndrome. J Immunol. 2008 Feb 01; 180(3):1921-8. View abstract
  87. Wang Z, Liu B, Wang P, Dong X, Fernandez-Hernando C, Li Z, Hla T, Li Z, Claffey K, Smith JD, Wu D. Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice. J Clin Invest. 2008 Jan; 118(1):195-204. View abstract
  88. Subbaramaiah K, Hudis C, Chang SH, Hla T, Dannenberg AJ. EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells. Evidence of a BRCA1 and p300 exchange. J Biol Chem. 2008 Feb 08; 283(6):3433-44. View abstract
  89. Skoura A, Sanchez T, Claffey K, Mandala SM, Proia RL, Hla T. Essential role of sphingosine 1-phosphate receptor 2 in pathological angiogenesis of the mouse retina. J Clin Invest. 2007 Sep; 117(9):2506-16. View abstract
  90. Ghosh M, Wang H, Ai Y, Romeo E, Luyendyk JP, Peters JM, Mackman N, Dey SK, Hla T. COX-2 suppresses tissue factor expression via endocannabinoid-directed PPARdelta activation. J Exp Med. 2007 Sep 03; 204(9):2053-61. View abstract
  91. Lee YM, Venkataraman K, Hwang SI, Han DK, Hla T. A novel method to quantify sphingosine 1-phosphate by immobilized metal affinity chromatography (IMAC). Prostaglandins Other Lipid Mediat. 2007 Nov; 84(3-4):154-62. View abstract
  92. Soldi R, Mandinova A, Venkataraman K, Hla T, Vadas M, Pitson S, Duarte M, Graziani I, Kolev V, Kacer D, Kirov A, Maciag T, Prudovsky I. Sphingosine kinase 1 is a critical component of the copper-dependent FGF1 export pathway. Exp Cell Res. 2007 Sep 10; 313(15):3308-18. View abstract
  93. Sanchez T, Skoura A, Wu MT, Casserly B, Harrington EO, Hla T. Induction of vascular permeability by the sphingosine-1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol. 2007 Jun; 27(6):1312-8. View abstract
  94. Kono M, Belyantseva IA, Skoura A, Frolenkov GI, Starost MF, Dreier JL, Lidington D, Bolz SS, Friedman TB, Hla T, Proia RL. Deafness and stria vascularis defects in S1P2 receptor-null mice. J Biol Chem. 2007 Apr 06; 282(14):10690-6. View abstract
  95. Oo ML, Thangada S, Wu MT, Liu CH, Macdonald TL, Lynch KR, Lin CY, Hla T. Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor. J Biol Chem. 2007 Mar 23; 282(12):9082-9. View abstract
  96. Gonzalez-Cabrera PJ, Hla T, Rosen H. Mapping pathways downstream of sphingosine 1-phosphate subtype 1 by differential chemical perturbation and proteomics. J Biol Chem. 2007 Mar 09; 282(10):7254-64. View abstract
  97. Hla T, Feinmark SJ. A festschrift for J. Martyn Bailey, a biochemist extraordinaire. Prostaglandins Other Lipid Mediat. 2007 Feb; 83(1-2):154-7. View abstract
  98. Kohno M, Momoi M, Oo ML, Paik JH, Lee YM, Venkataraman K, Ai Y, Ristimaki AP, Fyrst H, Sano H, Rosenberg D, Saba JD, Proia RL, Hla T. Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation. Mol Cell Biol. 2006 Oct; 26(19):7211-23. View abstract
  99. Lee JF, Zeng Q, Ozaki H, Wang L, Hand AR, Hla T, Wang E, Lee MJ. Dual roles of tight junction-associated protein, zonula occludens-1, in sphingosine 1-phosphate-mediated endothelial chemotaxis and barrier integrity. J Biol Chem. 2006 Sep 29; 281(39):29190-200. View abstract
  100. Venkataraman K, Thangada S, Michaud J, Oo ML, Ai Y, Lee YM, Wu M, Parikh NS, Khan F, Proia RL, Hla T. Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient. Biochem J. 2006 Aug 01; 397(3):461-71. View abstract
  101. Michaud J, Kohno M, Proia RL, Hla T. Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice. FEBS Lett. 2006 Aug 21; 580(19):4607-12. View abstract
  102. Thompson B, Ancellin N, Fernandez SM, Hla T, Sha'afi RI. Protein kinase Calpha and sphingosine 1-phosphate-dependent signaling in endothelial cell. Prostaglandins Other Lipid Mediat. 2006 Jul; 80(1-2):15-27. View abstract
  103. Subbaramaiah K, Howe LR, Port ER, Brogi E, Fishman J, Liu CH, Hla T, Hudis C, Dannenberg AJ. HER-2/neu status is a determinant of mammary aromatase activity in vivo: evidence for a cyclooxygenase-2-dependent mechanism. Cancer Res. 2006 May 15; 66(10):5504-11. View abstract
  104. Kitano M, Hla T, Sekiguchi M, Kawahito Y, Yoshimura R, Miyazawa K, Iwasaki T, Sano H, Saba JD, Tam YY. Sphingosine 1-phosphate/sphingosine 1-phosphate receptor 1 signaling in rheumatoid synovium: regulation of synovial proliferation and inflammatory gene expression. Arthritis Rheum. 2006 Mar; 54(3):742-53. View abstract
  105. Lee JF, Ozaki H, Zhan X, Wang E, Hla T, Lee MJ. Sphingosine-1-phosphate signaling regulates lamellipodia localization of cortactin complexes in endothelial cells. Histochem Cell Biol. 2006 Sep; 126(3):297-304. View abstract
  106. LaMontagne K, Littlewood-Evans A, Schnell C, O'Reilly T, Wyder L, Sanchez T, Probst B, Butler J, Wood A, Liau G, Billy E, Theuer A, Hla T, Wood J. Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Cancer Res. 2006 Jan 01; 66(1):221-31. View abstract
  107. Howe LR, Chang SH, Tolle KC, Dillon R, Young LJ, Cardiff RD, Newman RA, Yang P, Thaler HT, Muller WJ, Hudis C, Brown AM, Hla T, Subbaramaiah K, Dannenberg AJ. HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-2 knockout mice. Cancer Res. 2005 Nov 01; 65(21):10113-9. View abstract
  108. Hla T. Immunology. Dietary factors and immunological consequences. Science. 2005 Sep 09; 309(5741):1682-3. View abstract
  109. Hla T. Genomic insights into mediator lipidomics. Prostaglandins Other Lipid Mediat. 2005 Sep; 77(1-4):197-209. View abstract
  110. Rapaka RS, Hla T, Dey SK. The dawn of lipidomics. Prostaglandins Other Lipid Mediat. 2005 Sep; 77(1-4):1-3. View abstract
  111. Chang SH, Ai Y, Breyer RM, Lane TF, Hla T. The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia. Cancer Res. 2005 Jun 01; 65(11):4496-9. View abstract
  112. Jo E, Sanna MG, Gonzalez-Cabrera PJ, Thangada S, Tigyi G, Osborne DA, Hla T, Parrill AL, Rosen H. S1P1-selective in vivo-active agonists from high-throughput screening: off-the-shelf chemical probes of receptor interactions, signaling, and fate. Chem Biol. 2005 Jun; 12(6):703-15. View abstract
  113. Lepley D, Paik JH, Hla T, Ferrer F. The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit tumor cell migration. Cancer Res. 2005 May 01; 65(9):3788-95. View abstract
  114. Narko K, Zweifel B, Trifan O, Ristimäki A, Lane TF, Hla T. COX-2 inhibitors and genetic background reduce mammary tumorigenesis in cyclooxygenase-2 transgenic mice. Prostaglandins Other Lipid Mediat. 2005 May; 76(1-4):86-94. View abstract
  115. Chang SH, Liu CH, Wu MT, Hla T. Regulation of vascular endothelial cell growth factor expression in mouse mammary tumor cells by the EP2 subtype of the prostaglandin E2 receptor. Prostaglandins Other Lipid Mediat. 2005 May; 76(1-4):48-58. View abstract
  116. Heinonen M, Bono P, Narko K, Chang SH, Lundin J, Joensuu H, Furneaux H, Hla T, Haglund C, Ristimäki A. Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma. Cancer Res. 2005 Mar 15; 65(6):2157-61. View abstract
  117. Sanchez T, Thangada S, Wu MT, Kontos CD, Wu D, Wu H, Hla T. PTEN as an effector in the signaling of antimigratory G protein-coupled receptor. Proc Natl Acad Sci U S A. 2005 Mar 22; 102(12):4312-7. View abstract
  118. Chae SS, Hla T. Inhibition of gene expression in vivo using multiplex siRNA. Methods Mol Biol. 2005; 309:197-203. View abstract
  119. Hla T. Physiological and pathological actions of sphingosine 1-phosphate. Semin Cell Dev Biol. 2004 Oct; 15(5):513-20. View abstract
  120. Knostman KA, Cho JY, Ryu KY, Lin X, McCubrey JA, Hla T, Liu CH, Di Carlo E, Keri R, Zhang M, Hwang DY, Kisseberth WC, Capen CC, Jhiang SM. Signaling through 3',5'-cyclic adenosine monophosphate and phosphoinositide-3 kinase induces sodium/iodide symporter expression in breast cancer. J Clin Endocrinol Metab. 2004 Oct; 89(10):5196-203. View abstract
  121. Chae SS, Paik JH, Furneaux H, Hla T. Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J Clin Invest. 2004 Oct; 114(8):1082-9. View abstract
  122. Paik JH, Skoura A, Chae SS, Cowan AE, Han DK, Proia RL, Hla T. Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes Dev. 2004 Oct 01; 18(19):2392-403. View abstract
  123. Sanchez T, Hla T. Structural and functional characteristics of S1P receptors. J Cell Biochem. 2004 Aug 01; 92(5):913-22. View abstract
  124. Brinkmann V, Cyster JG, Hla T. FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant. 2004 Jul; 4(7):1019-25. View abstract
  125. Chae SS, Paik JH, Allende ML, Proia RL, Hla T. Regulation of limb development by the sphingosine 1-phosphate receptor S1p1/EDG-1 occurs via the hypoxia/VEGF axis. Dev Biol. 2004 Apr 15; 268(2):441-7. View abstract
  126. Saba JD, Hla T. Point-counterpoint of sphingosine 1-phosphate metabolism. Circ Res. 2004 Apr 02; 94(6):724-34. View abstract
  127. Jang BC, Kim DH, Park JW, Kwon TK, Kim SP, Song DK, Park JG, Bae JH, Mun KC, Baek WK, Suh MH, Hla T, Suh SI. Induction of cyclooxygenase-2 in macrophages by catalase: role of NF-kappaB and PI3K signaling pathways. Biochem Biophys Res Commun. 2004 Apr 02; 316(2):398-406. View abstract
  128. Chae SS, Proia RL, Hla T. Constitutive expression of the S1P1 receptor in adult tissues. Prostaglandins Other Lipid Mediat. 2004 Jan; 73(1-2):141-50. View abstract
  129. Hla T. Prostaglandins & other lipid mediators: a new phase, a new team. Prostaglandins Other Lipid Mediat. 2004 Jan; 73(1-2):1-2. View abstract
  130. Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, Lane TF, Hla T. Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci U S A. 2004 Jan 13; 101(2):591-6. View abstract
  131. Erkinheimo TL, Lassus H, Sivula A, Sengupta S, Furneaux H, Hla T, Haglund C, Butzow R, Ristimäki A. Cytoplasmic HuR expression correlates with poor outcome and with cyclooxygenase 2 expression in serous ovarian carcinoma. Cancer Res. 2003 Nov 15; 63(22):7591-4. View abstract
  132. Sanchez T, Estrada-Hernandez T, Paik JH, Wu MT, Venkataraman K, Brinkmann V, Claffey K, Hla T. Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. J Biol Chem. 2003 Nov 21; 278(47):47281-90. View abstract
  133. Hla T. Signaling and biological actions of sphingosine 1-phosphate. Pharmacol Res. 2003 May; 47(5):401-7. View abstract
  134. Sengupta S, Jang BC, Wu MT, Paik JH, Furneaux H, Hla T. The RNA-binding protein HuR regulates the expression of cyclooxygenase-2. J Biol Chem. 2003 Jul 04; 278(27):25227-33. View abstract
  135. Inaba T, Sano H, Kawahito Y, Hla T, Akita K, Toda M, Yamashina I, Inoue M, Nakada H. Induction of cyclooxygenase-2 in monocyte/macrophage by mucins secreted from colon cancer cells. Proc Natl Acad Sci U S A. 2003 Mar 04; 100(5):2736-41. View abstract
  136. Donohue PJ, Richards CM, Brown SA, Hanscom HN, Buschman J, Thangada S, Hla T, Williams MS, Winkles JA. TWEAK is an endothelial cell growth and chemotactic factor that also potentiates FGF-2 and VEGF-A mitogenic activity. Arterioscler Thromb Vasc Biol. 2003 Apr 01; 23(4):594-600. View abstract
  137. Kluk MJ, Colmont C, Wu MT, Hla T. Platelet-derived growth factor (PDGF)-induced chemotaxis does not require the G protein-coupled receptor S1P1 in murine embryonic fibroblasts and vascular smooth muscle cells. FEBS Lett. 2003 Jan 02; 533(1-3):25-8. View abstract
  138. Ozaki H, Hla T, Lee MJ. Sphingosine-1-phosphate signaling in endothelial activation. J Atheroscler Thromb. 2003; 10(3):125-31. View abstract
  139. Jang BC, Muñoz-Najar U, Paik JH, Claffey K, Yoshida M, Hla T. Leptomycin B, an inhibitor of the nuclear export receptor CRM1, inhibits COX-2 expression. J Biol Chem. 2003 Jan 31; 278(5):2773-6. View abstract
  140. Bishop-Bailey D, Hla T, Warner TD. Intimal smooth muscle cells as a target for peroxisome proliferator-activated receptor-gamma ligand therapy. Circ Res. 2002 Aug 09; 91(3):210-7. View abstract
  141. Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G. International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol Rev. 2002 Jun; 54(2):265-9. View abstract
  142. Kluk MJ, Hla T. Signaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled receptors. Biochim Biophys Acta. 2002 May 23; 1582(1-3):72-80. View abstract
  143. Ancellin N, Colmont C, Su J, Li Q, Mittereder N, Chae SS, Stefansson S, Liau G, Hla T. Extracellular export of sphingosine kinase-1 enzyme. Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation. J Biol Chem. 2002 Feb 22; 277(8):6667-75. View abstract