Ed Conway (Director)

Contact InformationEdC_29Aug2014
UBC Centre for Blood Research, Director
Life Sciences Centre
#4306, 2350 Health Sciences Mall
Vancouver, BC, Canada V6T 1Z3
Tel +1-604-822-4252
Fax +1-604-822-7742
Cell +1-778-960-7617
ed.conway@ubc.ca

Current Positions

  • Director, Centre for Blood Research
  • Professor of Medicine, University of British Columbia
  • Canada Research Chair in Endothelial Cell Biology
  • CSL-Behring Research Chair
  • Staff Physician, Division of Hematology, Department of Medicine, VCH
  • Adjunct Scientist, Canadian Blood Services
  • Member – Experimental Medicine, Pathology and Laboratory Medicine

Research Interests

Defining the molecular links between coagulation and innate immunity

Throughout evolution, organisms have developed means to simultaneously contain wounds by limiting bleeding with clot formation and fighting pathogens, thereby enabling rapid healing. Disease emerges when there is unchecked activation of the innate immune and/or coagulation responses. Indeed, simultaneous excess coagulation and innate immune responses are evident in numerous diseases, including, for example, atherosclerosis, stroke, coronary heart disease and diabetes, as well as organ ischemia-reperfusion, the metabolic syndrome, and other vasculopathic disorders, such as age-related macular degeneration, and hemolytic-uremic syndrome.

With the discovery that common molecular mechanisms regulate coagulation and inflammation, the last decades have seen major progress in identifying the cellular and molecular links. However, there remain major gaps in our knowledge and new discoveries are urgently needed for the development of novel strategies to prevent and/or treat cardiovascular disease and stroke. In our lab, we characterize the interplay between coagulation and complement, seeking relevant applications to our discoveries, using pre-clinical and clinical modeling approaches.

The perplexing story of the “tumor endothelial marker”, endosialin (CD248)

Endosialin (CD248) was originally identified as a tumor endothelial marker, but is now recognized to be expressed on the surface of activated stromal cells. This multi-domain glycoprotein is only expressed under pathologic conditions. Mice that lack CD248 are less sensitive to pro-inflammatory and oncogenic stimuli. We have determined that the cytoplasmic domain of CD248 modulates intracellular signals that promote tumor growth and inflammation. Ongoing studies are designed to identify molecular mechanisms by which CD248 functions, the protein partners with which CD248 interacts, and the wider impact of changes in expression of CD248. The findings may provide novel avenues for therapeutic targeting.

Publications (selected)

  1. Bellac CL. Dufour A, Krisinger M, Loonchanta A, Starr AE, auf dem Keller U, Lange PF, Goebeler V, Kappelhoff RG, Butler GS, Burtnick LD, Conway EM, Roberts CR, Overall CM. Macrophage Matrix Metalloproteinase-12 Dampens Inflammation and Neutrophil Recruitment in Arthritis: Pleiotropic Roles Revealed by TAILS Proteomics. Cell Reports 2014, S2211-1247(14)00774-8.PMID: 25310974
  2. Yu K, Lai BFL, Foley JH, Krisinger MJ, Conway EM, Kizhakkedathu JN. Modulation of Complement Activation and Amplification on Nanoparticle Surfaces by Glycopolymer Conformation and Chemistry. American Chem Society (ACS) Nano. 2014, Aug 26;8(8):7687-703
  3. Fukuda S, Hoggatt J, Singh P, Abe M, Speth JM, Hu P, Conway EM, Nucifora G, Yamaguchi S, Pelus LM. Survivin Modulates Genes with Divergent Molecular Functions and Regulates Proliferation of Hematopoietic Stem Cells through Evi-1. Leukemia. In Press Jun 2014. PMID 24903482
  4. Cassis P, Solini S, Azzollini B, Aiello S, Rocchetta F, Conti S, Novelli R, Gagliardini E, Mister M, Rapezzi S, Rapezzi F, Benigni A, Remuzzi G, Conway EM, Noris M. An unanticipated role for survivin in organ transplant damage. American J Transplant. (USA) 2014. May;14(5):1046-60. PMID: 24731002
  5. Kager LM, Wiersinga WJ, Roelofs JJTH, Stroo I, Achouiti A, Conway EM, van ‘t Veer C, van der Poll T. Mice lacking the lectin-like domain of thrombomodulin are protected against Gram-negative sepsis (melioidosis). Critical Care Medicine 2014 Mar;42(3):e221-30.
  6. Suresh Babu S, Valdez Y, Xu A, O’Byrne, Calvo F, Lei V, Conway EM. TGFb-mediated suppression of CD248 via canonical Smad-dependent signaling pathays is uncoupled in cancer cells. BMC Cancer 2014 Feb 20;14(1):113 PMID: 24555435
  7. Wat JM, Foley JH, Krisinger MJ, Ocariza LM, Lei V, Wasney GA, Lameignere E, Strynadka NC, Smith SA, Morrissey JH, Conway EM. Polyphosphate suppresses complement via the terminal pathway. Blood. 2014 Jan 30;123(5):768-76.
  8. Iscru E, Ahmed T, Coremans V, Bozzi Y, Caleo M, Conway EM, D’Hooge R, Balschun D. Loss of survivin in neural precursor cells results in impaired long-term potentiation in the dentate gyrus and CA1 region. Neuroscience 2013. 231:413-419.
  9. Foley JH, Conway EM. Gas6 gains entry into the coagulation cascade. Blood 2013. 121(4):570-1.
  10. Hageman S, Wohlschlaeger J, Bertram S, Levkau B, Musacchio A, Conway EM, Moellmann D, Kneiseler G, Pless-Petig G, Lorenz K, Sitec B, Baba HA. Loss of survivin influences liver regeneration due to impaired Aurora B function. Cell Death and Differentiation 2013. In Press. PMID: 2351907
  11. Gang EJ, Hsieh Y-T, Pham J, Zhao Y, Nguyen C, Huantes S, Park E, Naing K,1 Klemm L, Swaminathan S, Conway EM, Pelus L, Crispino J, Mullighan C, MacMillan M, Müschen M, Kahn M, Kim Y-M. Small molecule inhibition of CBP/catenin interactions eliminates drug resistant clones in acute lymphoblastic leukemia. Oncogene 2014. Apr 24;33(17):2169-78. PMID:23728349
  12. Chen J, Chen J-K, Conway EM, Harris RC. Survivin mediates recovery of renal proximal tubule epithelial cells following acute kidney injury. J American Society of Nephrology 2013.  Dec;24(12):2023-33. PMID: 23949800
  13. Adisetiyo H, Liang M, Liao C-P, Aycock-Williams A, Cohen MB, Xu S, Neamati N, Conway EM, Cheng C-Y, Nikitin AY, Roy-Burman P. Loss of survivin in the prostate epithelium impedes carcinogenesis in a mouse model of prostate adenocarcinoma.  PLOS One 2013. Jul 31;8(7):e69484. PMID: 23936028
  14. Li D, Cen J, Conway EM, Ji Y, Hui L. Hepatic loss of Survivin impairs liver development and promotes expansion of hepatic progenitor cells. Hepatology 2013. 58(6):2109-21. PMID: 23813590
  15. Foubert K, Breynaert A, Theunis M, Van Den Bossche R, De Meyer GR, Van Daele A, Faizal A, Goossens A, Geelen D, Conway EM, Vlietinck A, Pieters L, Apers S. Evaluation of the anti-angiogenic activity of saponins from Maesa lanceolata by different assays.Nature Prod Communications 2012 7(9):1149-54
  16. Wang H, Vinnikov I, He T, Zhou Q, Shahzad K, Ranjan S, Wolter J, Kashif M, Oh J, Kirschfink M, Bierhaus A, Nawroth P, Conway EM, Madhusudhan T, Isermann B.  The lectin-like domain of thrombomodulin ameliorates complement dependent diabetic nephropathy. Thromb Haemost 2012,108(6):1141-53.
  17. Iscru E, Ahmed T, Coremans V, Bozzi Y, Caleo M, Conway EM, D’Hooge R, Balschun D. Loss of survivin in neural precursor cells results in impaired long-term potentiation in the dentate gyrus and CA1 region. Neuroscience 2012 231:413-419.
  18. Zoja C, Locatelli M, Pagani C, Corna D, Isermann B, Remuzzi G, Conway EM, Noris M. Lack of the lectin-like domain of thrombomodulin worsens shiga toxin-associated HUS in mice.  J. Immunology 2012. 189(7):3661-8.
  19. Schouten M, de Boer JD, van t Veer C, Roelofs JJTH, Meijers JCM, Levi MM, Conway EM, van der Poll T. The lectin-like domain of thrombomodulin hampers host defense in pneumoccoccal pneumonia. Eur Resp J 2012. Aug 30.
  20. Krisinger M, Goebeler V, Lu Z, Meixner SC, Myles T, Pryzdial ELG, Conway EM. Revising the terminal complement pathway: Thrombin generates previously unidentified C5 products which augment lytic activity. Blood 2012. 120(8):1717-25.
  21. Conway EM.  Thrombomodulin and its role in inflammation.  Seminars Immunopath. 2012. 34(1):107-125.
  22. Valdez Y, Maia M, Conway EM. CD248: Reviewing its role in health and disease.  Curr Drug Targets 2012. Mar;13(3):432-439.
  23. Conway EM. The Type XIV family of C-type lectin-like domain (CTLD) containing proteins.  Curr Drug Targets 2012. Mar;13(3):409-410.
  24. Conway EM. The clock is ticking as the clot is thickening.  Arterioscler Thromb Vasc Biology. 2011. 31(11):2361-3
  25. Martinez-Gutierrez F, Thi E, Silverman M, Camargo C, Svensson S, Vanden Hoek A, Reiner N, Gaynor E, Pryzdial ELG, Conway EM, Orrantia E, Ruiz F, Av-Gay Y, Bach H.  Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanomedicine: Nanotechnology, Biology, and Medicine 2012; 8(3):328-336.
  26. Park E, Jiang E, Hsieh YT, Schaefer P, Klemm L, Loh M, Conway EM, Kang ES, Koo HH, Heisterkamp N, Pelus L, Keerthivasan G, Crispino J, Kahn M, Muschen M, Kim Y.  Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. Blood 2011. 118(8):2191-9.
  27. Horowitz NA, Blevins EA, Miller WM, Perry AR, Talmage KE, Mullins ES, Flick MJ, Queiroz KCS, Shi K, Spek CA, Conway EM, Monia BP, Weiler H, Degen JL, Palumbo JS. Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain. Blood 2011. 118(10):2889-95.
  28. Maia M, DeVriese A, Janssens T, Moons M, Lories RJ, Tavernier J, Conway EM. CD248 facilitates tumor growth via its cytoplasmic domain.  BMC Cancer 2011, 11:162.
  29. Takagi T, Taguchi O, D’Alessandro-Gabazza C, Toda M, Kobayashi T, Ruiz DB, Bernabe PG, Aoki S, Chiba F, Yano Y, Conway EM, Munesue S, Yamamoto Y, Yamamoto H, Suzuki K, Takei Y, Morser J, Gabazza EC. Inhibition of allergic bronchial asthma by thrombomodulin is mediated by dendritic cells. Am J Resp Critical Care Med 2011. 183(1):31-42.
  30. Maia M, DeVriese A, Janssens T, Moons M, Van Landuyt K, Tavernier J, Lories RJ, Conway EM. CD248 and its cytoplasmic domain: a therapeutic target for arthritis. Arthritis & Rheumatism 2010. 62(12):3595-606.
  31. Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Sorosina A, Castelletti F, Piras R, Donadelli R, Marant R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G. Relative role of genetic complement abnormalities in sporadic and familial aHUS. Clin. J. Am Soc Neph. 2010. 5(10): 1844-59.
  32. Conway EM. Super factor B”-gets atypical HUS.  Blood 2009.  114(13):2572-4
  33. Delvaeye M, Conway EM. Coagulation and innate Immune responses: Can they be viewed separately?  Blood 2009. 114(2):2367-74.
  34. Delvaeye M, De Vriese A, Esmon CT, Esmon N, Ferrell G, Claes B, Lambrechts D, Remuzzi G, Noris M, Conway EM. Mutations in thrombomodulin in hemolytic-uremic syndrome. New England Journal of Medicine (IF 51) 361:345-357, 2009.

Education

  • Ph.D. (Biomedical Sciences), University of Leuven (KUL), Belgium, 2006
  • M.B.A., Heriot Watt University, Scotland, 2004
  • FACP, Harvard University, Boston, 1984
  • FRCP(C), University of Toronto, 1984
  • M.D., University of Toronto, 1979
  • B.A.Sc. (Electrical Engineering), University of Toronto, 1975

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