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Research Newsletter - December 2007

Spotlight Article

SOCS3 Protein Developmentally Regulates the Chemokine Receptor CXCR4-FAK Signaling Pathway during B Lymphopoiesis

This month's spotlighted article is by HSCI Principal Faculty Member Les Silberstein of Children's Hospital Boston.

The chemokine receptor CXCR4 plays an important role in the localization of hematopoietic stem and progenitor cells within the extravascular compartment of the bone marrow. However, the mechanism by which stem and progenitor cells lodge and migrate between niches is not known. By investigating developing B cell populations in the bone marrow, Le et al. demonstrate that the suppressor of cytokine signaling 3 (SOCS3) protein developmentally regulates CXCR4-induced Focal Adhesion Kinase signaling and pro-adhesive cellular responses. The studies provide a mechanism whereby low levels of SOCS3 allow for the retention of progenitor B cells in the endosteal niche for prolonged periods for growth and differentiation, whereas high amounts of SOCS3 in mature B cells promote their migration to the central medullary region and subsequent exit into the peripheral circulation. A better understanding of the signals that control the residence and movement of stem/progenitor cells in the bone marrow should offer insight into previously unrecognized pathogenetic mechanims of leukemogenesis and immunodeficiency.

Le Y, Zhu BM, Harley B, Park SY, Kobayashi T, Manis JP, Luo HR, Yoshimura A, Hennighausen L, Silberstein LE. SOCS3 Protein Developmentally Regulates the Chemokine Receptor CXCR4-FAK Signaling Pathway during B Lymphopoiesis. Immunity. 2007 Nov;27(5):811-23. Read Abstract.

Scientific Papers

Review and Commentary

  • Ptaszek LM, Cowan CA. New Tools for Genome Modification in Human Embryonic Stem Cells. Cell Stem Cell. 2007 Dec 13:1(6):600-602. Read Abstract.
  • Scadden DT. The weight of cell identity. J Clin Invest. 2007 Dec;117(12):3653-5. Read Abstract.

Cancer

  • Del Gaizo Moore V, Schlis KD, Sallan SE, Armstrong SA, Letai A. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood. 2007 Dec 4. Read Abstract.
  • Fr√ɬ∂hling S, Scholl C, Levine RL, Loriaux M, Boggon TJ, Bernard OA, Berger R, D√ɬ∂hner H, D√ɬ∂hner K, Ebert BL, Teckie S, Golub TR, Jiang J, Schittenhelm MM, Lee BH, Griffin JD, Stone RM, Heinrich MC, Deininger MW, Druker BJ, Gilliland DG. Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles. Cancer Cell. 2007 Dec;12(6):501-13. Read Abstract.
  • Gee MS, Upadhyay R, Bergquist H, Weissleder R, Josephson L, Mahmood U. Multiparameter noninvasive assessment of treatment susceptibility, drug target inhibition and tumor response guides cancer treatment. Int J Cancer. 2007 Dec 1;121(11):2492-500. Read Abstract.
  • Gounaris E, Erdman SE, Restaino C, Gurish MF, Friend DS, Gounari F, Lee DM, Zhang G, Glickman JN, Shin K, Rao VP, Poutahidis T, Weissleder R, McNagny KM, Khazaie K. Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci USA. 2007 Dec 11;104(50):19977-82. Read Abstract.
  • Li Z, Tognon CE, Godinho FJ, Yasaitis L, Hock H, Herschkowitz JI, Lannon CL, Cho E, Kim SJ, Bronson RT, Perou CM, Sorensen PH, Orkin SH. ETV6-NTRK3 Fusion Oncogene Initiates Breast Cancer from Committed Mammary Progenitors via Activation of AP1 Complex. Cancer Cell. 2007 Dec;12(6):542-58. Read Abstract.
  • Swanson KD, Winter JM, Reis M, Bentires-Alj M, Greulich H, Grewal R, Hruban RH, Yeo CJ, Yassin Y, Iartchouk O, Montgomery K, Whitman SP, Caligiuri MA, Loh ML, Gilliland DG, Look AT, Kucherlapati R, Kern SE, Meyerson M, Neel BG. SOS1 mutations are rare in human malignancies: Implications for Noonan syndrome patients. Genes Chromosomes Cancer. 2007 Dec 6;47(3):253-259. Read Abstract.

Cardiovascular System

  • Yamamoto R, Akazawa H, Ito K, Toko H, Sano M, Yasuda N, Qin Y, Kudo Y, Sugaya T, Chien KR, Komuro I. Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-deficient mice. Circ J. 2007 Dec;71(12):1958-64. Read Abstract.

Developmental Biology

  • Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2007 Dec 23. Read Abstract.
  • Rompani SB, Cepko CL. Retinal progenitor cells can produce restricted subsets of horizontal cells. Proc Natl Acad Sci USA. 2007 Dec 27. Read Abstract.

Diabetes

  • Marselli L, Thorne J, Ahn YB, Omer A, Sgroi DC, Libermann T, Otu HH, Sharma A, Bonner-Weir S, Weir GC. Gene expression of purified beta cell tissue obtained from human pancreas with laser capture microdissection. J Clin Endocrinol Metab. 2007 Dec 11. Read Abstract.
  • Papas KK, Pisania A, Wu H, Weir GC, Colton CK. A stirred microchamber for oxygen consumption rate measurements with pancreatic islets. Biotechnol Bioeng. 2007 Dec 1;98(5):1071-82. Read Abstract.

Imaging

  • Bouffard J, Kim Y, Swager TM, Weissleder R, Hilderbrand SA. A highly selective fluorescent probe for thiol bioimaging. Org Lett. 2008 Jan 3;10(1):37-40. Epub 2007 Dec 7. Read Abstract.
  • Harisinghani M, Ross RW, Guimaraes AR, Weissleder R. Utility of a new bolus-injectable nanoparticle for clinical cancer staging. Neoplasia. 2007 Dec;9(12):1160-5. Read Abstract.
  • Korngold EC, Jaffer FA, Weissleder R, Sosnovik DE. Noninvasive imaging of apoptosis in cardiovascular disease. Heart Fail Rev. 2007 Dec 12. Read Abstract.
  • Nahrendorf M, Zhang H, Hembrador S, Panizzi P, Sosnovik DE, Aikawa E, Libby P, Swirski FK, Weissleder R. Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis. Circulation. 2007 Dec 24. Read Abstract.

Immunology

  • Noor S, Goldfine H, Tucker DE, Suram S, Lenz LL, Akira S, Uematsu S, Girotti M, Bonventre JV, Breuel K, Williams DL, Leslie CC. Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2. J Biol Chem. 2007 Dec 14. Read Abstract.

Nervous System

  • Chang BS, Katzir T, Liu T, Corriveau K, Barzillai M, Apse KA, Bodell A, Hackney D, Alsop D, Wong S, Walsh CA. A structural basis for reading fluency: white matter defects in a genetic brain malformation. Neurology. 2007 Dec 4;69(23):2146-54. Read Abstract.
  • Gao X, Arlotta P, Macklis JD, Chen J. Conditional knock-out of beta-catenin in postnatal-born dentate gyrus granule neurons results in dendritic malformation. J Neurosci. 2007 Dec 26;27(52):14317-25. Read Abstract.
  • Rajab A, Manzini MC, Mochida GH, Walsh CA, Ross ME. A novel form of lethal microcephaly with simplified gyral pattern and brain stem hypoplasia. Am J Med Genet A. 2007 Dec 1;143(23):2761-7. Read Abstract.

Renal System

  • Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2007 Dec 5. Read Abstract.
  • van Timmeren MM, Vaidya VS, van Ree RM, Oterdoom LH, de Vries AP, Gans RO, van Goor H, Stegeman CA, Bonventre JV, Bakker SJ. High Urinary Excretion of Kidney Injury Molecule-1 Is an Independent Predictor of Graft Loss in Renal Transplant Recipients. Transplantation. 2007 Dec 27;84(12):1625-1630. Read Abstract.
  • Zhang PL, Rothblum LI, Han WK, Blasick TM, Potdar S, Bonventre JV. Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury. Kidney Int. 2007 Dec 26. Read Abstract.

Technology

  • Wang J, Theunissen TW, Orkin SH. Site-directed, virus-free, and inducible RNAi in embryonic stem cells. Proc Natl Acad Sci USA. 2007 Dec 26;104(52):20850-5. Read Abstract.