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Research Newsletter - May 2007

Spotlight

In an article paper published in Nature Neuroscience, HSCI Principal Faculty Member, Kevin Eggan and Tom Maniatis, a professor in Harvard's Faculty of Arts and Sciences, report that a factor produced by a form of glial cells causes the damage in motor neurons associated with ALS.

Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model

Here we report an in vitro model system for studying the molecular and cellular mechanisms that underlie the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Embryonic stem cells (ESCs) derived from mice carrying normal or mutant transgenic alleles of the human SOD1 gene were used to generate motor neurons by in vitro differentiation. These motor neurons could be maintained in long-term coculture either with additional cells that arose during differentiation or with primary glial cells. Motor neurons carrying either the nonpathological human SOD1 transgene or the mutant SOD1G93A allele showed neurodegenerative properties when cocultured with SOD1G93A glial cells. Thus, our studies demonstrate that glial cells carrying a human SOD1G93A mutation have a direct, non-cell autonomous effect on motor neuron survival. More generally, our results show that ESC-based models of disease provide a powerful tool for studying the mechanisms of neural degeneration. These phenotypes displayed in culture could provide cell-based assays for the identification of new ALS drugs.

Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K . Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci . 2007 May;10(5):608-614. Epub 2007 Apr 15. Read Abstract.

Scientific Papers

Review and Commentary

  • Chien KR. Molecular medicine: microRNAs and the tell-tale heart. Nature. 2007 May 24;447(7143):389-90. Read Abstract.
  • Sohn RL, Jain M, Liao R. Adult stem cells and heart regeneration. Expert Rev Cardiovasc Ther. 2007 May;5(3):507-17. Review. Read Abstract.

Blood

  • Chiaretti S, Tavolaro S, Ghia EM, Ariola C, Matteucci C, Elia L, Maggio R, Messina M, Ricciardi MR, Vitale A, Ritz J, Mecucci C, Guarini A, Foa R. Characterization of ABL1 expression in adult T-cell acute lymphoblastic leukemia by oligonucleotide array analysis. Haematologica. 2007 May;92(5):619-26. Read Abstract.
  • Pardanani A, Hood J, Lasho T, Levine RL, Martin MB, Noronha G, Finke C, Mak CC, Mesa R, Zhu H, Soll R, Gilliland DG, Tefferi A. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia. 2007 May 31. Read Abstract.
  • Raz T, Nardi V, Azam M, Cortes J, Daley GQ. Farnesyl transferase inhibitor resistance probed by target mutagenesis. Blood. 2007 May 29. Read Abstract.
  • Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA, Barosi G, Verstovsek S, Birgegard G, Mesa R, Reilly JT, Gisslinger H, Vannucchi AM, Cervantes F, Finazzi G, Hoffman R, Gilliland DG, Bloomfield CD, Vardiman JW. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007 May 8; Read Abstract.

Cancer

  • Le X, Langenau DM, Keefe MD, Kutok JL, Neuberg DS, Zon LI. Heat shock-inducible Cre/Lox approaches to induce diverse types of tumors and hyperplasia in transgenic zebrafish. Proc Natl Acad Sci USA. 2007 May 29;104(22):9410-5. Read Abstract.
  • Parini CL, Mathis D, Leath CA 3rd. Occult metastatic lung carcinoma presenting as locally advanced uterine carcinosarcoma on positron emission tomography/computed tomography imaging. Int J Gynecol Cancer. 2007 May-Jun;17(3):731-4. Read Abstract.
  • Weishaupt C, Munoz KN, Buzney E, Kupper TS, Fuhlbrigge RC. T-cell distribution and adhesion receptor expression in metastatic melanoma. Clin Cancer Res. 2007 May 1;13(9):2549-56. Read Abstract.

Cardiovascular System

  • Nicola S, Risebro CA, Melville AA, Moses K, Schwartz RJ, Chien KR, Riley PR. Thymosin {beta}4 is essential for coronary vessel development and promotes neovascularisation via adult epicardium. Ann N Y Acad Sci. 2007 May 10; Read Abstract.

Developmental Biology

  • Allen BL, Tenzen T, McMahon AP. The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. Genes Dev. 2007 May 15;21(10):1244-57. Read Abstract.
  • Fujino A, Pieretti-Vanmarcke R, Wong A, Donahoe PK, Arango NA. Sexual dimorphism of g-protein subunit Gng13 expression in the cortical region of the developing mouse ovary. Dev Dyn. 2007 May 11;236(7):1991-1996 Read Abstract.
  • Kantarci S, Donahoe PK. Congenital diaphragmatic hernia (CDH) etiology as revealed by pathway genetics. Am J Med Genet C Semin Med Genet. 2007 May 15;145(2):217-26. Read Abstract.
  • Langenau DM, Keefe MD, Storer NY, Guyon JR, Kutok JL, Le X, Goessling W, Neuberg DS, Kunkel LM, Zon LI. Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes Dev. 2007 Jun 1;21(11):1382-95. Read Abstract.
  • Lu W, Quintero-Rivera F, Fan Y, Alkuraya FS, Donovan DJ, Xi Q, Turbe-Doan A, Li QG, Campbell CG, Shanske AL, Sherr EH, Ahmad A, Peters R, Rilliet B, Parvex P, Bassuk AG, Harris DJ, Ferguson H, Kelly C, Walsh CA, Gronostajski RM, Devriendt K, Higgins A, Ligon AH, Quade BJ, Morton CC, Gusella JF, Maas RL. NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects. PLoS Genet. 2007 May 25;3(5):e80. Read Abstract.
  • Park JS, Valerius MT, McMahon AP. Wnt/{beta}-catenin signaling regulates nephron induction during mouse kidney development. Development. 2007 Jul;134(13):2533-9. Read Abstract.

Diabetes

  • Papas KK, Pisania A, Wu H, Weir GC, Colton CK. A stirred microchamber for oxygen consumption rate measurements with pancreatic islets. Biotechnol Bioeng. 2007 May 11. Read Abstract.
  • Yatoh S, Dodge R, Akashi T, Omer A, Sharma A, Weir GC, Bonner-Weir S. Differentiation of affinity-purified human pancreatic duct cells to {beta}--cells. Diabetes. 2007 May 1. Read Abstract.

Imaging

  • Alencar H, Funovics MA, Figueiredo J, Sawaya H, Weissleder R, Mahmood U. Colonic Adenocarcinomas: Near-Infrared Microcatheter Imaging of Smart Probes for Early Detection--Study in Mice. Radiology. 2007 May 16; Read Abstract.
  • Kozloff KM, Weissleder R, Mahmood U. Non-Invasive Optical Detection of Bone Mineral. J Bone Miner Res. 2007 May 8. Read Abstract.

Immunology

  • De Jager PL, Franchimont D, Waliszewska A, Bitton A, Cohen A, Langelier D, Belaiche J, Vermeire S, Farwell L, Goris A, Libioulle C, Jani N, Dassopoulos T, Bromfield GP, Dubois B, Cho JH, Brant SR, Duerr RH, Yang H, Rotter JI, Silverberg MS, Steinhart AH, Daly MJ, Podolsky DK, Louis E, Hafler DA, Rioux JD. The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases. Genes Immun. 2007 May 31. Read Abstract.

Muscular System

  • Mizuno Y, Guyon JR, Ishii A, Hoshino S, Ohkoshi N, Tamaoka A, Okamoto K, Kunkel LM. Beta-synemin expression in cardiotoxin-injected rat skeletal muscle. BMC Musculoskelet Disord. 2007 May 10;8:40. Read Abstract.

Nervous System

  • Marneros AG, She H, Zambarakji H, Hashizume H, Connolly EJ, Kim I, Gragoudas ES, Miller JW, Olsen BR. Endogenous endostatin inhibits choroidal neovascularization. FASEB J. 2007 May 25. Read Abstract.

Technology

  • Viney TJ, Balint K, Hillier D, Siegert S, Boldogkoi Z, Enquist LW, Meister M, Cepko CL, Roska B. Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Curr Biol. 2007 Jun 5;17(11):981-8. Read Abstract.