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profileDavid Brian Sykes, M.D., Ph.D.

TitleInstructor in Medicine
InstitutionMassachusetts General Hospital
DepartmentMedicine
AddressMassachusetts General Hospital
Dept of Medicine/Oncology, CPZN 4400
185 Cambridge St
Boston MA 02114
Phone6177245780
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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.
K08CA201640     (SYKES, DAVID B)Apr 1, 2017 - Mar 31, 2021
NIH/NCI
Developing differentiation therapy for the treatment of patients with acute myeloid leukemia
Role: Principal Investigator

R03DA032471     (SYKES, DAVID B)Jul 1, 2011 - Jun 30, 2014
NIH/NIDA
Discovering small molecules that overcome differentiation arrest in acute myeloid
Role: Principal Investigator

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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.
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  1. Lee PY, Sykes DB, Ameri S, Kalaitzidis D, Charles JF, Nelson-Maney N, Wei K, Cunin P, Morris A, Cardona AE, Root DE, Scadden DT, Nigrovic PA. The metabolic regulator mTORC1 controls terminal myeloid differentiation. Sci Immunol. 2017 May 26; 2(11). PMID: 28763796.
    View in: PubMed
  2. Kalaitzidis D, Lee D, Efeyan A, Kfoury Y, Nayyar N, Sykes DB, Mercier FE, Papazian A, Baryawno N, Victora GD, Neuberg D, Sabatini DM, Scadden DT. Amino acid-insensitive mTORC1 regulation enables nutritional stress resilience in hematopoietic stem cells. J Clin Invest. 2017 Apr 03; 127(4):1405-1413. PMID: 28319048.
    View in: PubMed
  3. Hahm E, Wei C, Fernandez I, Li J, Tardi NJ, Tracy M, Wadhwani S, Cao Y, Peev V, Zloza A, Lusciks J, Hayek SS, O'Connor C, Bitzer M, Gupta V, Sever S, Sykes DB, Scadden DT, Reiser J. Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease. Nat Med. 2017 Jan; 23(1):100-106. PMID: 27941791.
    View in: PubMed
  4. Lewis TA, Sykes DB, Law JM, Muñoz B, Rustiguel JK, Nonato MC, Scadden DT, Schreiber SL. Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia. ACS Med Chem Lett. 2016 Dec 08; 7(12):1112-1117. PMID: 27994748.
    View in: PubMed
  5. Sykes DB, Kfoury YS, Mercier FE, Wawer MJ, Law JM, Haynes MK, Lewis TA, Schajnovitz A, Jain E, Lee D, Meyer H, Pierce KA, Tolliday NJ, Waller A, Ferrara SJ, Eheim AL, Stoeckigt D, Maxcy KL, Cobert JM, Bachand J, Szekely BA, Mukherjee S, Sklar LA, Kotz JD, Clish CB, Sadreyev RI, Clemons PA, Janzer A, Schreiber SL, Scadden DT. Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia. Cell. 2016 Sep 22; 167(1):171-186.e15. PMID: 27641501.
    View in: PubMed
  6. Palchaudhuri R, Saez B, Hoggatt J, Schajnovitz A, Sykes DB, Tate TA, Czechowicz A, Kfoury Y, Ruchika F, Rossi DJ, Verdine GL, Mansour MK, Scadden DT. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol. 2016 Jul; 34(7):738-45. PMID: 27272386.
    View in: PubMed
  7. Mercier FE, Sykes DB, Scadden DT. Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1(STEM) Mouse. Stem Cell Reports. 2016 Jun 14; 6(6):985-92. PMID: 27185283; PMCID: PMC4911492.
  8. Lee D, Wang YH, Kalaitzidis D, Ramachandran J, Eda H, Sykes DB, Raje N, Scadden DT. Endogenous transmembrane protein UT2 inhibits pSTAT3 and suppresses hematological malignancy. J Clin Invest. 2016 Apr 01; 126(4):1300-10. PMID: 26927669; PMCID: PMC4811118.
  9. Chen E, Ahn JS, Sykes DB, Breyfogle LJ, Godfrey AL, Nangalia J, Ko A, DeAngelo DJ, Green AR, Mullally A. RECQL5 Suppresses Oncogenic JAK2-Induced Replication Stress and Genomic Instability. Cell Rep. 2015 Dec 22; 13(11):2345-52. PMID: 26686625; PMCID: PMC4691544.
  10. Kenderian SS, Rosado FG, Sykes DB, Hoyer JD, Lacy MQ. Long-term complete clinical and hematological responses of the TEMPI syndrome after autologous stem cell transplantation. Leukemia. 2015 Dec; 29(12):2414-6. PMID: 26500143.
    View in: PubMed
  11. Yoon KW, Byun S, Kwon E, Hwang SY, Chu K, Hiraki M, Jo SH, Weins A, Hakroush S, Cebulla A, Sykes DB, Greka A, Mundel P, Fisher DE, Mandinova A, Lee SW. Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53. Science. 2015 Jul 31; 349(6247):1261669. PMID: 26228159.
    View in: PubMed
  12. Lang D, Mead JS, Sykes DB. Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a pituitary adenoma. J Gen Intern Med. 2015 May; 30(5):692-6. PMID: 25583570; PMCID: PMC4395613.
  13. Belizaire R, Sykes DB, Chen YB, Spitzer TR, Makar RS. Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency. Transfusion. 2015 Sep; 55(9):2142-8. PMID: 25911963.
    View in: PubMed
  14. Sykes DB, Nichols DN. There Is No Denying It, Our Medical Language Needs an Update. J Grad Med Educ. 2015 Mar; 7(1):137-8. PMID: 26217448; PMCID: PMC4507913.
  15. Chattopadhyay S, Stewart AL, Mukherjee S, Huang C, Hartwell KA, Miller PG, Subramanian R, Carmody LC, Yusuf RZ, Sykes DB, Paulk J, Vetere A, Vallet S, Santo L, Cirstea DD, Hideshima T, Dancík V, Majireck MM, Hussain MM, Singh S, Quiroz R, Iaconelli J, Karmacharya R, Tolliday NJ, Clemons PA, Moore MA, Stern AM, Shamji AF, Ebert BL, Golub TR, Raje NS, Scadden DT, Schreiber SL. Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors. Cell Rep. 2015 Feb 04. PMID: 25660025.
    View in: PubMed
  16. Gupta S, Fenves A, Nance ST, Sykes DB, Dzik WS. Hyperhemolysis syndrome in a patient without a hemoglobinopathy, unresponsive to treatment with eculizumab. Transfusion. 2015 Mar; 55(3):623-8. PMID: 25257194.
    View in: PubMed
  17. Rosado FG, Oliveira JL, Sohani AR, Schroyens W, Sykes DB, Kenderian SS, Lacy MQ, Kyle RA, Hoyer JD. Bone marrow findings of the newly described TEMPI syndrome: when erythrocytosis and plasma cell dyscrasia coexist. Mod Pathol. 2015 Mar; 28(3):367-72. PMID: 25216227.
    View in: PubMed
  18. Khan J, Sykes DB. Case report: a 37-year-old male with telangiectasias, polycythemia vera, perinephric fluid collections, and intrapulmonary shunting. BMC Hematol. 2014; 14(1):11. PMID: 25143825; PMCID: PMC4138393.
  19. Wu L, Walas S, Leung W, Sykes DB, Wu J, Lo EH, Lok J. Neuregulin1-ß decreases IL-1ß-induced neutrophil adhesion to human brain microvascular endothelial cells. Transl Stroke Res. 2015 Apr; 6(2):116-24. PMID: 24863743; PMCID: PMC4247352.
  20. Singh H, Lane AA, Correll M, Przychodzen B, Sykes DB, Stone RM, Ballen KK, Amrein PC, Maciejewski J, Attar EC. Putative RNA-splicing gene LUC7L2 on 7q34 represents a candidate gene in pathogenesis of myeloid malignancies. Blood Cancer J. 2013 May 24; 3:e117. PMID: 23708642; PMCID: PMC3674458.
  21. Mansour MK, Tam JM, Khan NS, Seward M, Davids PJ, Puranam S, Sokolovska A, Sykes DB, Dagher Z, Becker C, Tanne A, Reedy JL, Stuart LM, Vyas JM. Dectin-1 activation controls maturation of ß-1,3-glucan-containing phagosomes. J Biol Chem. 2013 May 31; 288(22):16043-54. PMID: 23609446; PMCID: PMC3668760.
  22. Simic P, Zainabadi K, Bell E, Sykes DB, Saez B, Lotinun S, Baron R, Scadden D, Schipani E, Guarente L. SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating ß-catenin. EMBO Mol Med. 2013 Mar; 5(3):430-40. PMID: 23364955; PMCID: PMC3598082.
  23. Schroyens W, O'Connell C, Sykes DB. Complete and partial responses of the TEMPI syndrome to bortezomib. N Engl J Med. 2012 Aug 23; 367(8):778-80. PMID: 22913703.
    View in: PubMed
  24. Park D, Sykes DB, Scadden DT. The hematopoietic stem cell niche. Front Biosci (Landmark Ed). 2012 Jan 01; 17:30-9. PMID: 22201730; PMCID: PMC4020275.
  25. Sykes DB, Schroyens W, O'Connell C. The TEMPI syndrome--a novel multisystem disease. N Engl J Med. 2011 Aug 04; 365(5):475-7. PMID: 21812700.
    View in: PubMed
  26. Scheele JS, Kolanczyk M, Gantert M, Zemojtel T, Dorn A, Sykes DB, Sykes DP, Möbest DC, Kamps MP, Räpple D, Duchniewicz M. The Spt-Ada-Gcn5-acetyltransferase complex interaction motif of E2a is essential for a subset of transcriptional and oncogenic properties of E2a-Pbx1. Leuk Lymphoma. 2009 May; 50(5):816-28. PMID: 19399691.
    View in: PubMed
  27. Odegaard JI, Vats D, Zhang L, Ricardo-Gonzalez R, Smith KL, Sykes DB, Kamps MP, Chawla A. Quantitative expansion of ES cell-derived myeloid progenitors capable of differentiating into macrophages. J Leukoc Biol. 2007 Mar; 81(3):711-9. PMID: 17158607; PMCID: PMC1904487.
  28. Wang GG, Calvo KR, Pasillas MP, Sykes DB, Häcker H, Kamps MP. Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8. Nat Methods. 2006 Apr; 3(4):287-93. PMID: 16554834.
    View in: PubMed
  29. Sykes DB, Kamps MP. E2a/Pbx1 induces the rapid proliferation of stem cell factor-dependent murine pro-T cells that cause acute T-lymphoid or myeloid leukemias in mice. Mol Cell Biol. 2004 Feb; 24(3):1256-69. PMID: 14729970; PMCID: PMC321418.
  30. Sykes DB, Scheele J, Pasillas M, Kamps MP. Transcriptional profiling during the early differentiation of granulocyte and monocyte progenitors controlled by conditional versions of the E2a-Pbx1 oncoprotein. Leuk Lymphoma. 2003 Jul; 44(7):1187-99. PMID: 12916872.
    View in: PubMed
  31. Sykes DB, Kamps MP. Estrogen-regulated conditional oncoproteins: tools to address open questions in normal myeloid cell function, normal myeloid differentiation, and the genetic basis of differentiation arrest in myeloid leukemia. Leuk Lymphoma. 2003 Jul; 44(7):1131-9. PMID: 12916864.
    View in: PubMed
  32. Welch JS, Escoubet-Lozach L, Sykes DB, Liddiard K, Greaves DR, Glass CK. TH2 cytokines and allergic challenge induce Ym1 expression in macrophages by a STAT6-dependent mechanism. J Biol Chem. 2002 Nov 08; 277(45):42821-9. PMID: 12215441.
    View in: PubMed
  33. Calvo KR, Sykes DB, Pasillas MP, Kamps MP. Nup98-HoxA9 immortalizes myeloid progenitors, enforces expression of Hoxa9, Hoxa7 and Meis1, and alters cytokine-specific responses in a manner similar to that induced by retroviral co-expression of Hoxa9 and Meis1. Oncogene. 2002 Jun 20; 21(27):4247-56. PMID: 12082612.
    View in: PubMed
  34. Klappacher GW, Lunyak VV, Sykes DB, Sawka-Verhelle D, Sage J, Brard G, Ngo SD, Gangadharan D, Jacks T, Kamps MP, Rose DW, Rosenfeld MG, Glass CK. An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation. Cell. 2002 Apr 19; 109(2):169-80. PMID: 12007404.
    View in: PubMed
  35. Calvo KR, Knoepfler PS, Sykes DB, Pasillas MP, Kamps MP. Meis1a suppresses differentiation by G-CSF and promotes proliferation by SCF: potential mechanisms of cooperativity with Hoxa9 in myeloid leukemia. Proc Natl Acad Sci U S A. 2001 Nov 06; 98(23):13120-5. PMID: 11687616; PMCID: PMC60834.
  36. Sykes DB, Kamps MP. Estrogen-dependent E2a/Pbx1 myeloid cell lines exhibit conditional differentiation that can be arrested by other leukemic oncoproteins. Blood. 2001 Oct 15; 98(8):2308-18. PMID: 11588024.
    View in: PubMed
  37. Knoepfler PS, Sykes DB, Pasillas M, Kamps MP. HoxB8 requires its Pbx-interaction motif to block differentiation of primary myeloid progenitors and of most cell line models of myeloid differentiation. Oncogene. 2001 Sep 06; 20(39):5440-8. PMID: 11571641.
    View in: PubMed
  38. Slupsky CM, Sykes DB, Gay GL, Sykes BD. The HoxB1 hexapeptide is a prefolded domain: implications for the Pbx1/Hox interaction. Protein Sci. 2001 Jun; 10(6):1244-53. PMID: 11369863; PMCID: PMC2374006.
  39. Calvo KR, Sykes DB, Pasillas M, Kamps MP. Hoxa9 immortalizes a granulocyte-macrophage colony-stimulating factor-dependent promyelocyte capable of biphenotypic differentiation to neutrophils or macrophages, independent of enforced meis expression. Mol Cell Biol. 2000 May; 20(9):3274-85. PMID: 10757811; PMCID: PMC85621.
  40. Mehta N, Hordines J, Sykes D, Doerr RJ, Cohen SA. Low density lipoproteins and Lovastatin modulate the organ-specific transendothelial migration of primary and metastatic human colon adenocarcinoma cell lines in vitro. Clin Exp Metastasis. 1998 Oct; 16(7):587-94. PMID: 9932605.
    View in: PubMed
  41. Parney IF, Petruk KC, Zhang C, Farr-Jones M, Sykes DB, Chang LJ. Granulocyte-macrophage colony-stimulating factor and B7-2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme model. Hum Gene Ther. 1997 Jun 10; 8(9):1073-85. PMID: 9189765.
    View in: PubMed
  42. Sykes D, Dewar R, Mohanaruban K, Donovan K, Nicklason F, Thomas DM, Fisher D. Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability? BMJ. 1990 Jan 20; 300(6718):162-3. PMID: 2105795; PMCID: PMC1662156.
  43. Wilson R, Pitt T, Taylor G, Watson D, MacDermot J, Sykes D, Roberts D, Cole P. Pyocyanin and 1-hydroxyphenazine produced by Pseudomonas aeruginosa inhibit the beating of human respiratory cilia in vitro. J Clin Invest. 1987 Jan; 79(1):221-9. PMID: 3098783; PMCID: PMC424027.
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