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Timothy T Hla, Ph.D.

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Biography
2016
Fellow of the AAAS
2015
MD(honoris causa), Goethe University
2015
Outstanding achievement award
2014
Siegel award for outstanding medical research, Weill Cornell Medical College
2007
Honorary Member, Japanese Biochemical Society
2006
MERIT award, NHLBI, NIH
1999
Established Investigator, AHA
1988 - 1991
Postdoctoral fellowship award, Arthritis Foundation

Overview
Tim 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 regulates 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 how this novel signaling pathway regulates vascular development, homeostasis and is dysregulated in vascular diseases. In addition, our work contributed to the development of S1P receptor inhibitors, which are being used for the 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. In fact, our laboratory is developing novel small molecules as well as protein biotherapeutics to modulate heart disease, stroke, autoimmune diseases, eye disease and cancer.

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01EY031715 (HLA, TIMOTHY TUN) May 1, 2021 - Mar 31, 2026
    NIH
    G protein-coupled receptor regulation of transcriptional mechanisms in the retinal vasculature.
    Role: Principal Investigator
  2. R56AG069825 (HLA, TIMOTHY TUN) Sep 15, 2020 - Aug 31, 2021
    NIH
    Sphingolipid signaling in age-associated vascular pathology
    Role: Principal Investigator
  3. 1R35HL135821 (Hla, Timothy) Jan 18, 2017 - Dec 31, 2023
    NIH/ NHLBI
    Mechanisms of sphingolipid signaling in vascular health and disease
    Role Description: Endothelial injury is a key event in cardiovascular disease, which is accelerated in autoimmune diseases such as systemic lupus erythematosus. This project will investigate a sphingosine 1-phosphate receptor on endothelial cells which is activated by normal blood flow as well as high density lipoproteins, with the aim of better understanding vascular diseases and to develop new therapies.
    Role: Pinciple Investigator
  4. R35HL135821 (HLA, TIMOTHY TUN) Jan 18, 2017 - Dec 31, 2023
    NIH
    Mechanisms of sphingolipid signaling in vascular health and disease
    Role: Principal Investigator
  5. Transatlantic Network Grant (Hla/ Betsholtz) Sep 1, 2014 - Aug 30, 2019
    Fondation Leducq
    Sphingolipid mediators in neurovascular biology and disease
    Role: Principle investigator

Featured Content

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Mao Y, Kleinjan ML, Jilishitz I, Swaminathan B, Obinata H, Komarova YA, Bayless KJ, Hla T, Kitajewski JK. CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function. Sci Signal. 2021 Apr 20; 14(679). PMID: 33879602.
    Citations:    Fields:    
  2. Hla T. Support Myanmar's embattled scientists and students. Nature. 2021 Apr; 592(7855):507. PMID: 33879888.
    Citations:    Fields:    
  3. Engelbrecht E, MacRae CA, Hla T. Lysolipids in Vascular Development, Biology, and Disease. Arterioscler Thromb Vasc Biol. 2020 Dec 17; ATVBAHA120305565. PMID: 33327749.
    Citations:    Fields:    
  4. Nitzsche A, Poittevin M, Benarab A, Bonnin P, Faraco G, Uchida H, Favre J, Garcia-Bonilla L, Garcia MCL, Léger PL, Thérond P, Mathivet T, Autret G, Baudrie V, Couty L, Kono M, Chevallier A, Niazi H, Tharaux PL, Chun J, Schwab SR, Eichmann A, Tavitian B, Proia RL, Charriaut-Marlangue C, Sanchez T, Kubis N, Henrion D, Iadecola C, Hla T, Camerer E. Endothelial S1P1 Signaling Counteracts Infarct Expansion in Ischemic Stroke. Circ Res. 2021 Feb 05; 128(3):363-382. PMID: 33301355.
    Citations: 1     Fields:    
  5. Geng X, Yanagida K, Akwii RG, Choi D, Chen L, Ho Y, Cha B, Mahamud MR, Berman de Ruiz K, Ichise H, Chen H, Wythe JD, Mikelis CM, Hla T, Srinivasan RS. S1PR1 regulates the quiescence of lymphatic vessels by inhibiting laminar shear stress-dependent VEGF-C signaling. JCI Insight. 2020 07 23; 5(14). PMID: 32544090.
    Citations: 4     Fields:    
  6. Ding BS, Yang D, Swendeman SL, Christoffersen C, Nielsen LB, Friedman SL, Powell CA, Hla T, Cao Z. Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair. Dev Cell. 2020 06 22; 53(6):677-690.e4. PMID: 32544390.
    Citations:    Fields:    Translation:AnimalsCells
  7. Engelbrecht E, Levesque MV, He L, Vanlandewijck M, Nitzsche A, Niazi H, Kuo A, Singh SA, Aikawa M, Holton K, Proia RL, Kono M, Pu WT, Camerer E, Betsholtz C, Hla T. Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta. Elife. 2020 02 24; 9. PMID: 32091396.
    Citations: 5     Fields:    Translation:AnimalsCells
  8. Yanagida K, Engelbrecht E, Niaudet C, Jung B, Gaengel K, Holton K, Swendeman S, Liu CH, Levesque MV, Kuo A, Fu Z, Smith LEH, Betsholtz C, Hla T. Sphingosine 1-Phosphate Receptor Signaling Establishes AP-1 Gradients to Allow for Retinal Endothelial Cell Specialization. Dev Cell. 2020 03 23; 52(6):779-793.e7. PMID: 32059774.
    Citations: 6     Fields:    Translation:AnimalsCells
  9. Pandey S, Banks KM, Kumar R, Kuo A, Wen D, Hla T, Evans T. Sphingosine kinases protect murine embryonic stem cells from sphingosine-induced cell cycle arrest. Stem Cells. 2020 05; 38(5):613-623. PMID: 31916656.
    Citations: 2     Fields:    
  10. Cartier A, Leigh T, Liu CH, Hla T. Endothelial sphingosine 1-phosphate receptors promote vascular normalization and antitumor therapy. Proc Natl Acad Sci U S A. 2020 02 11; 117(6):3157-3166. PMID: 31988136.
    Citations: 8     Fields:    Translation:AnimalsCells
  11. Subbaramaiah K, Hudis C, Chang SH, Hla T, Dannenberg AJ. Withdrawal: EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells: Evidence of a BRCA1 and p300 exchange. J Biol Chem. 2020 01 03; 295(1):295. PMID: 31900377.
    Citations:    Fields:    
  12. Subbaramaiah K, Hudis C, Chang SH, Hla T, Dannenberg AJ. Withdrawal: EP2 and EP4 receptors regulate aromatase expression in human adipocytes and breast cancer cells: Evidence of a BRCA1 and p300 exchange. J Biol Chem. 2020 Jan 03; 295(1):295. PMID: 33518006.
    Citations:    Fields:    
  13. Poganik JR, Long MJC, Disare MT, Liu X, Chang SH, Hla T, Aye Y. Post-transcriptional regulation of Nrf2-mRNA by the mRNA-binding proteins HuR and AUF1. FASEB J. 2019 12; 33(12):14636-14652. PMID: 31665914.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  14. Cartier A, Hla T. Sphingosine 1-phosphate: Lipid signaling in pathology and therapy. Science. 2019 10 18; 366(6463). PMID: 31624181.
    Citations: 27     Fields:    Translation:HumansAnimalsCells
  15. Singh RK, Haka AS, Asmal A, Barbosa-Lorenzi VC, Grosheva I, Chin HF, Xiong Y, Hla T, Maxfield FR. TLR4 (Toll-Like Receptor 4)-Dependent Signaling Drives Extracellular Catabolism of LDL (Low-Density Lipoprotein) Aggregates. Arterioscler Thromb Vasc Biol. 2020 01; 40(1):86-102. PMID: 31597445.
    Citations: 8     Fields:    Translation:AnimalsCells
  16. Obinata H, Kuo A, Wada Y, Swendeman S, Liu CH, Blaho VA, Nagumo R, Satoh K, Izumi T, Hla T. Identification of ApoA4 as a sphingosine 1-phosphate chaperone in ApoM- and albumin-deficient mice. J Lipid Res. 2019 11; 60(11):1912-1921. PMID: 31462513.
    Citations: 3     Fields:    Translation:AnimalsCells
  17. Obinata H, Hla T. Sphingosine 1-phosphate and inflammation. Int Immunol. 2019 08 23; 31(9):617-625. PMID: 31049553.
    Citations: 20     Fields:    Translation:HumansAnimalsCells
  18. Tsai HC, Nguyen K, Hashemi E, Engleman E, Hla T, Han MH. Myeloid sphingosine-1-phosphate receptor 1 is important for CNS autoimmunity and neuroinflammation. J Autoimmun. 2019 12; 105:102290. PMID: 31202617.
    Citations: 2     Fields:    Translation:AnimalsCells
  19. Inoue T, Kohno M, Nagahara H, Murakami K, Sagawa T, Kasahara A, Kaneshita S, Kida T, Fujioka K, Wada M, Nakada H, Hla T, Kawahito Y. Upregulation of sphingosine-1-phosphate receptor 3 on fibroblast-like synoviocytes is associated with the development of collagen-induced arthritis via increased interleukin-6 production. PLoS One. 2019; 14(6):e0218090. PMID: 31173610.
    Citations: 4     Fields:    Translation:AnimalsCells
  20. Hisano Y, Kono M, Cartier A, Engelbrecht E, Kano K, Kawakami K, Xiong Y, Piao W, Galvani S, Yanagida K, Kuo A, Ono Y, Ishida S, Aoki J, Proia RL, Bromberg JS, Inoue A, Hla T. Lysolipid receptor cross-talk regulates lymphatic endothelial junctions in lymph nodes. J Exp Med. 2019 07 01; 216(7):1582-1598. PMID: 31147448.
    Citations: 8     Fields:    Translation:HumansAnimalsCells
  21. Shi X, Wang W, Li J, Wang T, Lin Y, Huang S, Kuver A, Chen C, Hla T, Li X, Dai K. Sphingosine 1-phosphate receptor 1 regulates cell-surface localization of membrane proteins in endothelial cells. Biochim Biophys Acta Gen Subj. 2019 06; 1863(6):1079-1087. PMID: 30954526.
    Citations: 1     Fields:    Translation:AnimalsCells
  22. Ban Y, Dong W, Zhang L, Zhou T, Altiti AS, Ali K, Mootoo DR, Blaho VA, Hla T, Ren Y, Ma X. Abrogation of Endogenous Glycolipid Antigen Presentation on Myelin-Laden Macrophages by D-Sphingosine Ameliorates the Pathogenesis of Experimental Autoimmune Encephalomyelitis. Front Immunol. 2019; 10:404. PMID: 30941120.
    Citations:    Fields:    Translation:AnimalsCells
  23. Xiong Y, Piao W, Brinkman CC, Li L, Kulinski JM, Olivera A, Cartier A, Hla T, Hippen KL, Blazar BR, Schwab SR, Bromberg JS. CD4 T cell sphingosine 1-phosphate receptor (S1PR)1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration. Sci Immunol. 2019 03 15; 4(33). PMID: 30877143.
    Citations: 12     Fields:    Translation:HumansAnimalsCells
  24. Swendeman SL, Hla T. Lipid Mediators, M2 Macrophages, and Pathological Neovascularization. Trends Mol Med. 2018 12; 24(12):977-978. PMID: 30448396.
    Citations:    Fields:    Translation:HumansAnimalsCells
  25. 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 11; 70(11):1879-1889. PMID: 29781582.
    Citations: 16     Fields:    Translation:HumansAnimalsCells
  26. Montrose DC, Zhou XK, McNally EM, Sue E, Wang H, Nishiguchi R, Verma A, Elemento O, Simpson KW, Yang P, Hla T, Dannenberg AJ. Colonoscopic-Guided Pinch Biopsies in Mice as a Useful Model for Evaluating the Roles of Host and Luminal Factors in Colonic Inflammation. Am J Pathol. 2018 12; 188(12):2811-2825. PMID: 30273600.
    Citations:    Fields:    Translation:AnimalsCells
  27. Hisano Y, Hla T. Bioactive lysolipids in cancer and angiogenesis. Pharmacol Ther. 2019 01; 193:91-98. PMID: 30048709.
    Citations: 18     Fields:    Translation:HumansAnimals
  28. 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. PMID: 29518138.
    Citations: 5     Fields:    Translation:AnimalsCells
  29. Yanagida K, Hla T. A dark side to omega-3 fatty acids. Nature. 2017 12 14; 552(7684):180-181. PMID: 29239390.
    Citations: 3     Fields:    Translation:Humans
  30. Yanagida K, Hla T. A dark side to omega-3 fatty acids. Nature. 2017 Dec; 552(7684):180-181. PMID: 32080455.
    Citations:    Fields:    
  31. 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 10 27; 8(1):1163. PMID: 29079828.
    Citations: 11     Fields:    Translation:AnimalsCells
  32. Mendelson K, Pandey S, Hisano Y, Carellini F, Das BC, 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. PMID: 28956531.
    Citations: 4     Fields:    Translation:Animals
  33. 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 10; 58(10):1977-1987. PMID: 28814641.
    Citations: 3     Fields:    Translation:AnimalsCells
  34. 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). PMID: 28811382.
    Citations: 22     Fields:    Translation:HumansAnimalsCells
  35. 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. PMID: 28654421.
    Citations: 2     Fields:    
  36. 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. PMID: 28607130.
    Citations: 19     Fields:    Translation:AnimalsCells
  37. Galvani S, Hla T. Quality Versus Quantity: Making HDL Great Again. Arterioscler Thromb Vasc Biol. 2017 06; 37(6):1018-1019. PMID: 28539490.
    Citations: 2     Fields:    Translation:Humans
  38. 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. PMID: 28538737.
    Citations: 44     Fields:    Translation:AnimalsCells
  39. 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. PMID: 28396408.
    Citations: 43     Fields:    Translation:AnimalsCells
  40. 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. PMID: 28018969.
    Citations: 18     Fields:    
  41. Yanagida K, Hla T. Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient. Annu Rev Physiol. 2017 02 10; 79:67-91. PMID: 27813829.
    Citations: 27     Fields:    Translation:HumansAnimals
  42. 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. PMID: 27582371.
    Citations: 22     Fields:    Translation:HumansAnimalsCells
  43. 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. PMID: 27226645.
    Citations: 3     Fields:    
  44. 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. PMID: 26956418.
    Citations: 23     Fields:    Translation:Animals
  45. 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. PMID: 26701909.
    Citations: 25     Fields:    Translation:AnimalsCells
  46. 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. PMID: 26501192.
    Citations: 74     Fields:    Translation:HumansAnimals
  47. 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. PMID: 26301690.
    Citations: 34     Fields:    Translation:HumansAnimalsCells
  48. 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. PMID: 26268607.
    Citations: 75     Fields:    Translation:HumansAnimalsCells
  49. 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. PMID: 25997406.
    Citations: 6     Fields:    Translation:Animals
  50. 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. PMID: 26105954.
    Citations: 7     Fields:    Translation:HumansAnimalsCells
  51. 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. PMID: 26053123.
    Citations: 64     Fields:    Translation:AnimalsCells
  52. 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. PMID: 25831442.
    Citations: 153     Fields:    Translation:HumansAnimals
  53. 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. PMID: 25533351.
    Citations: 22     Fields:    Translation:HumansAnimalsCells
  54. 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. PMID: 25422430.
    Citations: 22     Fields:    Translation:AnimalsCells
  55. Hla T, Kolesnick R. C16:0-ceramide signals insulin resistance. Cell Metab. 2014 Nov 04; 20(5):703-705. PMID: 25440051.
    Citations: 28     Fields:    Translation:HumansAnimals
  56. 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. PMID: 25293589.
    Citations: 10     Fields:    Translation:HumansAnimalsCells
  57. 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. PMID: 25250575.
    Citations: 32     Fields:    Translation:AnimalsCells
  58. 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. PMID: 25198418.
    Citations: 13     Fields:    Translation:AnimalsCells
  59. 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. PMID: 25176650.
    Citations: 21     Fields:    Translation:AnimalsCells
  60. 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. PMID: 25085247.
    Citations: 22     Fields:    Translation:Animals
  61. 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. PMID: 25440790.
    Citations: 56     Fields:    Translation:HumansCells
  62. 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. PMID: 24597601.
    Citations: 46     Fields:    Translation:HumansAnimalsCells
  63. 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. PMID: 25092091.
    Citations: 3     Fields:    Translation:HumansCells
  64. Chang SH, Hla T. Post-transcriptional gene regulation by HuR and microRNAs in angiogenesis. Curr Opin Hematol. 2014 May; 21(3):235-40. PMID: 24714527.
    Citations: 18     Fields:    Translation:Humans
  65. 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. PMID: 24679864.
    Citations: 7     Fields:    Translation:Animals
  66. Blaho VA, Hla T. An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res. 2014 Aug; 55(8):1596-608. PMID: 24459205.
    Citations: 128     Fields:    Translation:HumansAnimalsCells
  67. 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. PMID: 24425803.
    Citations: 13     Fields:    Translation:HumansAnimalsCells
  68. Xiong Y, Hla T. S1P control of endothelial integrity. Curr Top Microbiol Immunol. 2014; 378:85-105. PMID: 24728594.
    Citations: 38     Fields:    Translation:HumansAnimalsCells
  69. Mendelson K, Evans T, Hla T. Sphingosine 1-phosphate signalling. Development. 2014 Jan; 141(1):5-9. PMID: 24346695.
    Citations: 89     Fields:    Translation:HumansCells
  70. 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):32563-32573. PMID: 24081141.
    Citations: 32     Fields:    Translation:AnimalsCells
  71. 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. PMID: 24076635.
    Citations: 55     Fields:    Translation:HumansAnimalsCells
  72. 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. PMID: 23704073.
    Citations: 17     Fields:    Translation:HumansAnimalsCells
  73. 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. PMID: 23624019.
    Citations: 12     Fields:    Translation:HumansAnimalsCells
  74. 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. PMID: 23296878.
    Citations: 18     Fields:    Translation:HumansAnimals
  75. 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. PMID: 23229546.
    Citations: 28     Fields:    Translation:AnimalsCells
  76. 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. PMID: 23223443.
    Citations: 28     Fields:    Translation:HumansAnimalsCells
  77. Hla T, Galvani S, Rafii S, Nachman R. S1P and the birth of platelets. J Exp Med. 2012 Nov 19; 209(12):2137-40. PMID: 23166370.
    Citations: 10     Fields:    Translation:Cells
  78. 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. PMID: 23056483.
    Citations: 4     Fields:    Translation:AnimalsCells
  79. Obinata H, Hla T. Fine-tuning S1P therapeutics. Chem Biol. 2012 Sep 21; 19(9):1080-2. PMID: 22999874.
    Citations: 6     Fields:    
  80. Hla T, Dannenberg AJ. Sphingolipid signaling in metabolic disorders. Cell Metab. 2012 Oct 03; 16(4):420-34. PMID: 22982021.
    Citations: 60     Fields:    Translation:HumansCells
  81. 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. PMID: 22975328.
    Citations: 107     Fields:    Translation:AnimalsCells
  82. 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. PMID: 22326262.
    Citations: 11     Fields:    Translation:HumansCells
  83. Moolenaar WH, Hla T. SnapShot: Bioactive lysophospholipids. Cell. 2012 Jan 20; 148(1-2):378-378.e2. PMID: 22265422.
    Citations: 18     Fields:    Translation:HumansAnimals
  84. 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. PMID: 22528440.
    Citations: 3     Fields:    Translation:HumansCells
  85. 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. PMID: 21939239.
    Citations: 69     Fields:    Translation:Animals
  86. Obinata H, Hla T. Sphingosine 1-phosphate in coagulation and inflammation. Semin Immunopathol. 2012 Jan; 34(1):73-91. PMID: 21805322.
    Citations: 59     Fields:    Translation:HumansAnimalsCells
  87. Chang SH, Hla T. Gene regulation by RNA binding proteins and microRNAs in angiogenesis. Trends Mol Med. 2011 Nov; 17(11):650-8. PMID: 21802991.
    Citations: 20     Fields:    Translation:HumansAnimalsCells
  88. 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. PMID: 21606363.
    Citations: 175     Fields:    Translation:HumansAnimalsCells
  89. Li MH, Hla T, Ferrer F. Sphingolipid modulation of angiogenic factor expression in neuroblastoma. Cancer Prev Res (Phila). 2011 Aug; 4(8):1325-32. PMID: 21576349.
    Citations: 9     Fields:    Translation:HumansAnimalsCells
  90. 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. PMID: 21555855.
    Citations: 83     Fields:    Translation:AnimalsCells
  91. 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. PMID: 21372033.
    Citations: 167     Fields:    Translation:HumansAnimalsCells
  92. 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. PMID: 21339489.
    Citations: 84     Fields:    Translation:HumansAnimals
  93. 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. PMID: 21079037.
    Citations: 114     Fields:    Translation:HumansAnimals
  94. 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. PMID: 20947824.
    Citations: 61     Fields:    Translation:AnimalsCells
  95. 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. PMID: 20584883.
    Citations: 72     Fields:    Translation:AnimalsCells
  96. 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):26825-26831. PMID: 20558741.
    Citations: 21     Fields:    Translation:HumansCells
  97. 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. PMID: 20042570.
    Citations: 59     Fields:    Translation:AnimalsCells
  98. Hla T, Oo ML. Ramping up RANTES in the acute response to arterial injury. J Clin Invest. 2010 Jan; 120(1):90-2. PMID: 20038805.
    Citations: 2     Fields:    Translation:AnimalsCells
  99. 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. PMID: 19884656.
    Citations: 83     Fields:    Translation:AnimalsCells
  100. Hla T. Plugging vascular leak by sphingosine kinase from bone marrow progenitor cells. Circ Res. 2009 Sep 25; 105(7):614-6. PMID: 19797192.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  101. 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. PMID: 19830907.
    Citations: 12     Fields:    Translation:HumansAnimalsCells
  102. Skoura A, Hla T. Regulation of vascular physiology and pathology by the S1P2 receptor subtype. Cardiovasc Res. 2009 May 01; 82(2):221-8. PMID: 19287048.
    Citations: 43     Fields:    Translation:HumansAnimalsCells
  103. Hla T, Im DS. Cell biology. The ABCs of lipophile transport. Science. 2009 Feb 13; 323(5916):883-4. PMID: 19213902.
    Citations: 2     Fields:    Translation:AnimalsCells
  104. 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. PMID: 19157443.
    Citations: 13     Fields:    Translation:HumansCells
  105. 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. PMID: 19131156.
    Citations: 29     Fields:    Translation:HumansCells
  106. 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. PMID: 19101649.
    Citations: 15     Fields:    Translation:Animals
  107. Skoura A, Hla T. Lysophospholipid receptors in vertebrate development, physiology, and pathology. J Lipid Res. 2009 Apr; 50 Suppl:S293-8. PMID: 19065000.
    Citations: 34     Fields:    Translation:HumansAnimals
  108. 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. PMID: 18922980.
    Citations: 27     Fields:    Translation:HumansCells
  109. 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. PMID: 18765664.
    Citations: 23     Fields:    Translation:HumansCells
  110. Hla T, Venkataraman K, Michaud J. The vascular S1P gradient-cellular sources and biological significance. Biochim Biophys Acta. 2008 Sep; 1781(9):477-82. PMID: 18674637.
    Citations: 72     Fields:    Translation:HumansAnimals
  111. 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. PMID: 18258856.
    Citations: 191     Fields:    Translation:HumansAnimalsCells
  112. 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. PMID: 18209090.
    Citations: 16     Fields:    Translation: