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Research Newsletter - Feburary 2009

Spotlight

In an article paper published in the journal Blood, HSCI Faculty Executive Committee Member Jerome Ritz, MD and colleagues report findings which delineate specific abnormalities of B cell homeostasis in patients with chronic graft versus host disease.

Altered B cell homeostasis and excess BAFF in human chronic graft versus host disease

Abstract:

Chronic graft versus host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of allo-antibodies and high plasma BAFF levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF:B cell ratios compared to patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre-germinal center (GC) B cells and post-GC 'plasmablast-like' cells, suggesting in vivo BAFF-dependence of these two CD27+ B cell subsets. Circulating CD27+ B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27+ B cells in the first year post-HSCT. These studies delineate specific abnormalities of B cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease.

  • Sarantopoulos S, Stevenson KE, Kim HT, Cutler CS, Bhuiya NS, Schowalter M, Ho VT, Alyea EP, Koreth J, Blazar BR, Soiffer RJ, Antin JH, Ritz J. Altered B cell homeostasis and excess BAFF in human chronic graft versus host disease. Blood. 2009 Jan 23. Read Paper.

Scientific Papers

Review and Commentary

  • Patapoutian A, Tate S, Woolf CJ. Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov. 2009 Jan;8(1):55-68. Review.

    Read Abstract.
  • Amabile G, Meissner A. Induced pluripotent stem cells: current progress and potential for regenerative medicine. Trends Mol Med. 2009 Jan 20. Read Abstract.
  • Bernt KM, Armstrong SA. Leukemia stem cells and human acute lymphoblastic leukemia. Semin Hematol. 2009 Jan;46(1):33-8. Read Abstract.
  • Daley GQ. Common Themes of Dedifferentiation in Somatic Cell Reprogramming and Cancer. Cold Spring Harb Symp Quant Biol. 2009 Jan 15. Read Abstract.
  • Donahoe PK, Noonan KM, Lage K. Genetic tools and algorithms for gene discovery in major congenital anomalies. Birth Defects Res A Clin Mol Teratol. 2009 Jan;85(1):6-12. Read Abstract.
  • Eisenberg I, Alexander MS, Kunkel LM. miRNAS in normal and diseased skeletal muscle. J Cell Mol Med. 2009 Jan;13(1):2-11. Read Abstract.
  • Lin L, Lesnick TG, Maraganore DM, Isacson O. Axon guidance and synaptic maintenance: preclinical markers for neurodegenerative disease and therapeutics. Trends Neurosci. 2009 Jan 20. Read Abstract.
  • Meissner A, Eminli S, Jaenisch R. Derivation and manipulation of murine embryonic stem cells. Methods Mol Biol. 2009;482:3-19. Read Abstract.
  • Park IH, Daley GQ. Human iPS cell derivation/reprogramming. Curr Protoc Stem Cell Biol. 2009 Jan;Chapter 4:Unit 4A.1. Read Abstract.
  • Shen X, Orkin SH Glimpses of the epigenetic landscape. Cell Stem Cell. 2009 Jan 9;4(1):1-2. Read Abstract.
  • Tulpule A, Daley GQ. Efficient gene knockdowns in human embryonic stem cells using lentiviral-based RNAi. Methods Mol Biol. 2009;482:35-42. Read Abstract.
  • Williams DA. ESCGT 2008: progress in clinical gene therapy. Mol Ther. 2009 Jan;17(1):1-2. Read Abstract.

Blood

  • Cornejo MG, Kharas MG, Werneck MB, Le Bras S, Moore SA, Ball B, Beylot-Barry M, Rodig SJ, Aster JC, Lee BH, Cantor H, Merlio JP, Gilliland DG, Mercher T. Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplant models. Blood. 2009 Jan 12. Read Abstract.
  • Nardi V, Naveiras O, Azam M, Daley GQ. ICSBP-mediated immune protection against BCR-ABL-induced leukemia requires the CCL6 and CCL9 chemokines. Blood. 2009 Jan 26. Read Abstract.
  • Sarantopoulos S, Stevenson KE, Kim HT, Cutler CS, Bhuiya NS, Schowalter M, Ho VT, Alyea EP, Koreth J, Blazar BR, Soiffer RJ, Antin JH, Ritz J. Altered B cell homeostasis and excess BAFF in human chronic graft versus host disease. Blood. 2009 Jan 23. Read Abstract.

Cancer

  • Cheong JK, Gunaratnam L, Zang ZJ, Yang CM, Sun X, Nasr SL, Sim KG, Peh BK, Rashid SB, Bonventre JV, Salto-Tellez M, Hsu SI. TRIP-Br2 promotes oncogenesis in nude mice and is frequently overexpressed in multiple human tumors. J Transl Med. 2009 Jan 20;7(1):8. Read Abstract.
  • Nardella C, Carracedo A, Alimonti A, Hobbs RM, Clohessy JG, Chen Z, Egia A, Fornari A, Fiorentino M, Loda M, Kozma SC, Thomas G, Cordon-Cardo C, Pandolfi PP. Differential Requirement of mTOR in Postmitotic Tissues and Tumorigenesis. Sci Signal. 2009 Jan 27;2(55):ra2. Read Abstract.

Developmental Biology

  • Chen B, Cepko CL. HDAC4 regulates neuronal survival in normal and diseased retinas. Science. 2009 Jan 9;323(5911):256-9. Read Abstract.
  • Liu Y, Chattopadhyay N, Qin S, Szekeres C, Vasylyeva T, Mahoney ZX, Taglienti M, Bates CM, Chapman HA, Miner JH, Kreidberg JA. Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis. Development. 2009 Jan 28. Read Abstract.
  • Sherwood RI, Chen TY, Melton DA. Transcriptional dynamics of endodermal organ formation. Dev Dyn. 2009 Jan;238(1):29-42. Read Abstract.
  • Yu J, Carroll TJ, Rajagopal J, Kobayashi A, Ren Q, McMahon AP. A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney. Development. 2009 Jan;136(1):161-71. Read Abstract.

Diabetes

  • Emamaullee JA, Merani S, Toso C, Kin T, Al-Saif F, Truong W, Pawlick R, Davis J, Edgar R, Lock J, Bonner-Weir S, Knudsen LB, Shapiro AM. Porcine marginal mass islet autografts resist metabolic failure over time and are enhanced by early treatment with liraglutide. Endocrinology. 2009 Jan 8. Read Abstract.
  • Nagaya M, Katsuta H, Kaneto H, Bonner-Weir S, Weir GC. Adult mouse intrahepatic biliary epithelial cells induced in vitro to become insulin-producing cells. J Endocrinol. 2009 Jan 27. Read Abstract.

Imaging

  • Devaraj NK, Keliher EJ, Thurber GM, Nahrendorf M, Weissleder R. (18)F Labeled Nanoparticles for in Vivo PET-CT Imaging. Bioconjug Chem. 2009 Jan 12. Read Abstract.
  • Garanger E, Weissleder R, Josephson L. A multifunctional single-attachment-point reagent for controlled protein biotinylation. Bioconjug Chem. 2009 Jan;20(1):170-3. Read Abstract.
  • Sheth RA, Upadhyay R, Stangenberg L, Sheth R, Weissleder R, Mahmood U. Improved detection of ovarian cancer metastases by intraoperative quantitative fluorescence protease imaging in a pre-clinical model. Gynecol Oncol. 2009 Jan 7. Read Abstract.

Immunology

  • Clatworthy AE, Lee JS, Leibman M, Kostun Z, Davidson AJ, Hung DT. Pseudomonas aeruginosa infection of zebrafish involves both host and pathogen determinants. Infect Immun. 2009 Jan 21. Read Abstract.

Pain

  • Amaya F, Samad TA, Barrett L, Broom DC, Woolf CJ. Periganglionic inflammation elicits a distally radiating pain hypersensitivity by promoting COX-2 induction in the dorsal root ganglion. Pain. 2009 Jan 8. Read Abstract.
  • Vardeh D, Wang D, Costigan M, Lazarus M, Saper CB, Woolf CJ, Fitzgerald GA, Samad TA. COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice. J Clin Invest. 2009 Jan 5. pii: 37098. doi: 10.1172/JCI37098. Read Abstract.