Photo of Akiko Shimamura,   MD, PhD

Akiko Shimamura, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 919-2508


akiko.shimamura@childrens.harvard.edu

Akiko Shimamura, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Pediatrics, Harvard Medical School
  • Director, Bone Marrow Failure and MDS Program, Dana Farber/Boston Children’s Cancer and Blood Disorders Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

I am studying the role of mitogen-activated protein kinases (MAPK's) in the reulation of cell proliferation and apoptosis. The serine/threonine kinase RSK is a target of the MAPK pathway. In the laboratory of Dr. John Blenis, I have identified a novel role for RSK in promoting cell survival. One mechanism for RSK-mediated cell survival is the direct phosphorylation and subsequent inactivation of BAD, a pro-apoptotic member of the Bcl-2 family. RSK has been reported to phosphorylate additional apoptosis regulatory proteins, such as CREB and IKB, so RSK likely promotes cell survival through pathways in addition to BAD. RSK also phosphorylates the cell cycle regulatory protein myt1. I am investigating the biochemical mechanisms regulating RSK activity. I am also conducting studies to identify interactions between RSK and other key regulatory kinases. Finally, I have developed a novel constitutively active RSK mutant and am conducting experiments to investigate RSK's role in oncogenesis both in cell culture and in tumors.

Publications

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  • Godley LA, Shimamura A. Genetic predisposition to hematologic malignancies: management and surveillance. Blood 2017. PubMed
  • Seo A, Ben-Harosh M, Sirin M, Stein J, Dgany O, Kaplelushnik J, Hoenig M, Pannicke U, Lorenz M, Schwarz K, Stockklausner C, Walsh T, Gulsuner S, Lee MK, Sendamarai A, Sanchez-Bonilla M, King MC, Cario H, Kulozik AE, Debatin KM, Schulz A, Tamary H, Shimamura A. Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in THPO. Blood 2017. PubMed
  • Hock H, Shimamura A. ETV6 in hematopoiesis and leukemia predisposition. Semin Hematol 2017; 54:98-104. PubMed
  • Furutani E, Shimamura A. Germline Genetic Predisposition to Hematologic Malignancy. J Clin Oncol 2017; 35:1018-1028. PubMed
  • Khincha PP, Bertuch AA, Agarwal S, Townsley DM, Young NS, Keel S, Shimamura A, Boulad F, Simoneau T, Justino H, Kuo C, Artandi S, McCaslin C, Cox DW, Chaffee S, Collins BF, Giri N, Alter BP, Raghu G, Savage SA. Pulmonary arteriovenous malformations: an uncharacterised phenotype of dyskeratosis congenita and related telomere biology disorders. Eur. Respir. J. 2016. PubMed
  • Shimamura A. Aplastic anemia and clonal evolution: germ line and somatic genetics. Hematology Am Soc Hematol Educ Program 2016; 2016:74-82. PubMed
  • Mamrak NE, Shimamura A, Howlett NG. Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia. Blood Rev. 2016. PubMed
  • Keel SB, Scott A, Sanchez-Bonilla M, Ho PA, Gulsuner S, Pritchard CC, Abkowitz JL, King MC, Walsh T, Shimamura A. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. Haematologica 2016. PubMed
  • Wong TE, Calicchio ML, Fleming MD, Shimamura A, Harris MH. SBDS protein expression patterns in the bone marrow. Pediatr Blood Cancer 2010; 55:546-9. PubMed
  • Rosenberg PS, Zeidler C, Bolyard AA, Alter BP, Bonilla MA, Boxer LA, Dror Y, Kinsey S, Link DC, Newburger PE, Shimamura A, Welte K, Dale DC. Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy. British Journal of Haematology 2010; 150:196-9. PubMed
  • Parmar K, Kim J, Sykes SM, Shimamura A, Stuckert P, Zhu K, Hamilton A, Deloach MK, Kutok JL, Akashi K, Gilliland DG, D'Andrea A. Hematopoietic Stem Cell Defects in Mice with Deficiency of Fancd2 or Usp1. Stem Cells 2010; 28:1186-95. PubMed
  • Shimamura A, Alter BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 2010; 24:101-22. PubMed
  • Tulpule A, Lensch MW, Miller JD, Austin K, D'Andrea A, Schlaeger TM, Shimamura A, Daley GQ. Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage. Blood 2010; 115:3453-62. PubMed
  • Sakamoto KM, Shimamura A, Davies SM. Congenital disorders of ribosome biogenesis and bone marrow failure. Biol Blood Marrow Transplant 2010; 16:S12-7. PubMed
  • Burroughs L,Woolfrey A,Shimamura A. Shwachman-Diamond syndrome: a review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment. Hematol Oncol Clin North Am 2009; 23:233-48. PubMed
  • Du HY,Pumbo E,Ivanovich J,An P,Maziarz RT,Reiss UM,Chirnomas D,Shimamura A,Vlachos A,Lipton JM,Goyal RK,Goldman F,Wilson DB,Mason PJ,Bessler M. TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements. Blood 2008; 113:309-16. PubMed
  • Park IH,Arora N,Huo H,Maherali N,Ahfeldt T,Shimamura A,Lensch MW,Cowan C,Hochedlinger K,Daley GQ. Disease-specific induced pluripotent stem cells. Cell 2008; 134:877-86. PubMed
  • Vlachos A,Ball S,Dahl N,Alter BP,Sheth S,Ramenghi U,Meerpohl J,Karlsson S,Liu JM,Leblanc T,Paley C,Kang EM,Leder EJ,Atsidaftos E,Shimamura A,Bessler M,Glader B,Lipton JM. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. British Journal of Haematology 2008; 142:859-76. PubMed
  • Shimamura A. Diamond-Blackfan anemia: a new facet. Blood 2008; 112:1552-3. PubMed
  • Kayed H,Bekasi S,Keleg S,Welsch T,Esposito I,Shimamura A,Michalski CW,Friess H,Kleeff J. Expression of the Shwachman-Bodian-Diamond syndrome (SBDS) protein in human pancreatic cancer and chronic pancreatitis. Histol Histopathol 2008; 23:819-26. PubMed
  • Austin KM, Gupta ML, Coats SA, Tulpule A, Mostoslavsky G, Balazs AB, Mulligan RC, Daley G, Pellman D, Shimamura A. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome. J Clin Invest 2008; 118:1511-8. PubMed
  • Ganapathi KA, Austin KM, Lee CS, Dias A, Malsch MM, Reed R, Shimamura A. The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA. Blood 2007; 110:1458-65. PubMed
  • Kennedy RD, Chen CC, Stuckert P, Archila EM, De la Vega MA, Moreau LA, Shimamura A, D'Andrea AD. Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of ataxia telangiectasia mutated. J Clin Invest 2007; 117:1440-9. PubMed
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