Zhang, MY, Churpek, JE, Walsh, T, Lee, MK, Keel, SB, Loeb, KR, Gulsuner, S, Pritchard, CC, Forouhar, M, Gyurkocza, B, Schwartz, BS, Neistadt, B, Marquez, R, Mariani, C, Coats, S, Hofmann, I, Lindsley, RC, Williams, DA, Abkowitz, JL, Horwitz, MS, Godley, LA, King, MC, and Shimamura, A. Germline ETV6 Mutations in Familial Thrombocytopenia and Hematologic Malignancy. Nature Genetics. 2015. 47(2): 180-185. PMID: 25581430
Topka S, Vijai J, Walsh MF, Jacobs L, Maria A, Villano D, Gaddam P, Wu G, McGee RB, Quinn E, Inaba H, Hartford C, Pui CH, Pappo A, Edmonson M, Zhang MY, Stepensky P, Steinherz P, Schrader K, Lincoln A, Bussel J, Lipkin SM, Goldgur Y, Harit M, Stadler ZK, Mullighan C, Weintraub M, Shimamura A, Zhang J, Downing JR, Nichols KE, Offit K. Germline ETV6 mutations confer susceptibility to acute lymphoblastic leukemia and thrombocytopenia. PLoS Genet. 2015. Jun 23; 11(6) e1005262. Doi 10.1371/journal.pgen.1005262. PMID 26102509.
Schmitz-Abe K, Ciesielski SJ, Schmidt PJ, Campagna DR, Rahimov F, Schilke BA, Cuijpers M, Rieneck K, Lausen B, Linenberger ML, Sendamarai AK, Guo C, Hofmann I, Newburger PE, Matthews D, Shimamura A, Snijders PJ, Towne MC, Niemeyer CM, Dziegiel MH, Heeney MM, May A, Bottomley SS, Swinkels DW, Markianos K, Craig EA, Fleming MD. Congenital sideroblastic anemia due to mutations in the mitochondrial HSP70 homologue HSPA9. Blood 2015. Dec 17; 126(25):2734-2738. PMID: 26491070
Lewinsohn M, Brown AL, Weinel LM, Phung C, Rafidi G, Lee MK, Schrieber AW, Feng J, Babic M, Chong CE, Lee Y, Yong A, Suthers GK, Poplawski N, Altree M, Phillips K, Jaensch L, Fine M, D’Andrea RJ, Lewis ID, Medeiros BC, Pollyea DA, King MC, Walsh T, Keel S, Shimamura A, Godley LA, Hahn CN, Churpek JN, Scott HS. Novel Germline DDX41 mutations define families with a lower age of MDS/AML onset and lymphoid malignancies. Blood 2016. Feb 25;127(8):1017-23 PMID: 26712909
Seo, A, Walsh, T, Lee, M, Ho, P, Hsu, E, Sidbury, R, King, MC, Shimamura, A. FAM111B mutation is associated with inherited exocrine pancreatic dysfunction. Pancreas 2016. Jul; 45(6):858-62. [PMID: 26495788]
Yang Z, Keel SB, Shimamura A, Liu L, Gerds AT, Li HY, Wood BL, Scott BL, Abkowitz JL. Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome. Sci Transl Med. 2016. May 11;8(338):338ra67. PMID: 27169803
Chen DH, Below JE, Shimamura A, Keel SB, Matsushita M, Wolff J, Sul Y, Bonkowski E, Castella M, Taniguchi T, Nickerson D, Papayannopoulou T, Bird TD, Raskind WH. Ataxia-Pancytopenia Syndrome is Caused by Missense Mutations in SAMD9L. Am J Hum Genet. 2016 Jun 2;98(6):1146-58. Doi: 10.1016/j.ajhg.2016.04.009. PMID: 27259050.
Rojek K, Nickels E, Neistadt B, Marquez R, Wickrema A, Artz A, van Besien K, Larson RA, Lee MK, Segal JP, King MC, Walsh T, Shimamura A, Keel SB, Churpek JE, Godley LA. Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell Mobilization and Donor-Derived Malignancy. Biol Blood Marrow Transplant. 2016 Nov;22(11):2100-2103. PMID: 27497531
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 Nov;101(11):1343-1350. PMID: 27418648
Burwick, N, Zhang MY, de la Puente P, Azab AK, Hyun TS, Ruiz-Gutierrez M, Sanchez-Bonilla M, Nakamura T, Delrow JJ, MacKay VL, Shimamura A. The eIF2-alpha kinase HRI is a novel therapeutic target in multiple myeloma. Leuk Res. 2017 Apr; 55:23-32. PMID: 28119225
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. 30(7):875-880. PMID: 28559357
Carapito R, Konantz M, Paillard C, Miao Z, Pichot A, Leduc MS, Yang Y, Bergstrom KL, Mahoney DH, Shardy DL, Alsaleh G, Naegely L, Kolmer A, Paul N, Hanauer A, Rolli V, Müller JS, Alghisi E, Sauteur L, Macquin C, Morlon A, Sancho CS, Amati-Bonneau P, Procaccio V, Mosca-Boidron AL, Marle N, Osmani N, Lefebvre O, Goetz JG, Unal S, Akarsu NA, Radosavljevic M, Chenard MP, Rialland F, Grain A, Béné MC, Eveillard M, Vincent M, Guy J, Faivre L, Thauvin-Robinet C, Thevenon J, Myers K, Fleming MD, Shimamura A, Bottollier-Lemallaz E, Westhof E, Lengerke C, Isidor B, Bahram S. Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-Diamond-like features. J Clin Invest. 2017 Nov 1;127(11):4090-4103. PMID: 28972538.
Xia J, Miller CA, Baty J, Ramesh A, Jotte MRM, Fulton RS, Vogel TP, Cooper MA, Walkovich KJ, Makaryan V, Bolyard AA, Dinauer MC, Wilson DB, Vlachos A, Myers KC, Rothbaum RJ, Bertuch AA, Dale DC, Shimamura A, Boxer LA, Link DC. Somatic mutations and clonal hematopoiesis in congenital neutropenia. Blood. 2018 Jan 25;131(4):408-416. PMID: 29092827.
Pastor VB, Sahoo SS, Boklan J, Schwabe GC, Saribeyoglu E, Strahm B, Lebrecht D, Voss M, Bryceson YT, Erlacher M, Ehninger G, Niewisch M, Schlegelberger B, Baumann I, Achermann JC, Shimamura A, Hochrein J, Tedgård U, Nilsson L, Hasle H, Boerries M, Busch H, Niemeyer CM, Wlodarski MW. Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7. Haematologica. 2018 Mar;103(3):427-437. PMID: 29217778
Whitaker, JR, Zhao, RG, Sanchez-Bonilla, M, Moore, HD, Schoenherr, RM, Yan, P, Lin, C, Shimamura, A, and Paulovich, AG. Targeted mass spectrometry enables robust quantification of FANCD2 mono-ubiquitination in response to DNA damage. DNA Repair (Amst). 2018 65:47-53. PMID 29605812
Seo A, Steinberg-Shemer O, Unal S, Casadei S, Walsh T, Gumruk F, Shalev S, Shimamura A, Akarsu NA, Tamary H, King M-C. Mechanism for survival of homozygous nonsense mutations in the tumor suppressor gene BRCA1. Proc Natl Acad Sci U S A. 2018 May 15;115(20):5241-5246. PMID: 29712865
Seo A. Gulsuner S, Pierce S, Ben-Harosh M, Shalev H, Walsh, T, Krasnov T, Dgany O, Doulatov S, Tamary, H, Shimamura A, King MC. Inherited thrombocytopenia associated with mutation of UDP-Galactose-4-Epimerase (GALE). Hum Mol Genet. 2019. 28(1): 133-142. PMID: 30247636
Ruiz-Gutierrez M, Vargel Bölükbaşi Ö, Alexe G, Kotini AG, Ballotti K, Joyce CE, Russell DW, Stegmaier K, Myers K, Novina CD, Papapetrou EP, Shimamura A. Therapeutic discovery for marrow failure with MDS predisposition using pluripotent stem cells. JCI Insight. 2019 Par 30; 5, pii: 125157. doi: 10.1172/jci.insight.125157. PMID: PMID:31039138
Joyce CE, Saadatpour A, Ruiz-Gutierrez M, Bolukbasi OV, Jiang L, Thomas DD, Young S, Hofmann I, Sieff C, Myers KC, Whangbo J, Libermann TA, Nusbaum C, Yuan GC, Shimamura A, Novina CD. TGFb signaling underlies hematopoietic dysfunction and bone marrow failure in Shwachman Diamond Syndrome. J Clin Invest 2019. 129(9): 3821-3826. PMID: 3121169
Chou DB, Frismantas V, Milton Y, David R, Pop-Damkov P, Ferguson D, MacDonald A, Vargel Bölükbaşı Ö, Joyce CE, Moreira Teixeira LS, Rech A, Jiang A, Calamari E, Jalili-Firoozinezhad S, Furlong BA, O'Sullivan LR, Ng CF, Choe Y, Marquez S, Myers KC, Weinberg OK, Hasserjian RP, Novak R, Levy O, Prantil-Baun R, Novina CD, Shimamura A, Ewart L, Ingber DE. On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat Biomed Eng. 2020. 4(4): 394-406. PMID: 31988457
Rodríguez A, Zhang K, Färkkilä A, Filiatrault J, Yang C, Velázquez M,, Furutani E, Goldman DC, García de Teresa B, Garza-Mayén G, McQueen K, Sambel LA, Molina B, Torres L, González M, Vadillo E, Pelayo R, Fleming WH, Grompe M, Shimamura A, Hautaniemi S, Greenberger J, Frías S, Parmar K, D'Andrea AD. MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia. Cell Stem Cell. 2020 Sep 24:S1934-5909(20)30450-1. doi: 10.1016/j.stem.2020.09.004. Epub ahead of print. PMID: 32997960.
Kumar S, Nattamai KJ, Hassan A, Amoah A, Karns R, Zhang C, Liang Y, Shimamura A, Florian MC, Bissels U, Luevano M, Bosio A, Davies SM, Mulaw M, Geiger H, Myers KC. Repolarization of HSC attenuates HSCs failure in Shwachman-Diamond syndrome. Leukemia. 2020 Oct 19. doi: 10.1038/s41375-020-01054-8. Epub ahead of print. PMID: 33077869.
Morton SU, Shimamura A, Newburger PE, Opotowsky AR, Quiat D, Pereira AC, Jin SC, Gurvitz M, Brueckner M, Chung WK, Shen Y, Bernstein D, Gelb BD, Giardini A, Goldmuntz E, Kim RW, Lifton RP, Porter GA Jr, Srivastava D, Tristani-Firouzi M, Newburger JW, Seidman JG, Seidman CE. Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease. JAMA Cardiol. 2020 Oct 21:e204947. doi: 10.1001/jamacardio.2020.4947. Epub ahead of print. PMID: 33084842; PMCID: PMC7578917.
Rodríguez A, Yang C, Furutani E, García de Teresa B, Velázquez M, Filiatrault, J, Sambel LA, Phan T, Flores-Guzmán P, Sánchez S, Monsiváis Orozco A, Mayani H, Bolukbasi OV, Färkkilä A, Epperly M, Greenberger J, Shimamura A, Frías S, Grompe M, Parmar K, D'Andrea AD. Inhibition of TGFβ1 and TGFβ3 promotes hematopoiesis in Fanconi anemia. Exp Hematol. 2020 Nov 7:S0301-472X(20)30620-2. doi:10.1016/j.exphem.2020.11.002. Epub ahead of print. PMID: 33166613
Rao S, Yao Y, Soares de Brito J, Yao Q, Shen AH, Watkinson RE, Kennedy AL, Coyne S, Ren C, Zeng J, Serbin AV, Studer S, Ballotti K, Harris CE, Luk K, Stevens CS, Armant M, Pinello L, Wolfe SA, Chiarle R, Shimamura A, Lee B, Newburger PE, Bauer DE. Dissecting ELANE neutropenia pathogenicity by human HSC gene editing. Cell Stem Cell. 2021 Jan 25:S1934-5909(20)30599-3. doi: 10.1016/j.stem.2020.12.015. Epub ahead of print. PMID: 33513358.
Kennedy AL, Myers KC, Bowman J, Gibson CJ, Camarda ND, Furutani E, Muscato GM, Klein RH, Ballotti K, Liu S, Harris CE, Galvin A, Malsch M, Dale D, Gansner JM, Nakano TA, Bertuch A, Vlachos A, Lipton JM, Castillo P, Connelly J, Churpek J, Edwards JR, Hijiya N, Ho RH, Hofmann I, Huang JN, Keel S, Lamble A, Lau BW, Norkin M, Stieglitz E, Stock W, Walkovich K, Boettcher S, Brendel C, Fleming MD, Davies SM, Weller EA, Bahl C, Carter SL, Shimamura A, Lindsley RC. Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome. Nat Commun. 2021 Feb 26;12(1):1334. doi: 10.1038/s41467-021-21588-4. PMID: 33637765; PMCID: PMC7910481.
Clinical Research
Williams, D, Bennett,, C, Bertuch, A, Bessler, M, Coates, T, Corey, S, Dror, Y, Huang, J, Lipton, J, Olson, TS, Reiss, UM, Rogers, ZR, Sieff, C, Vlachos, A, Walkovich, K, Wang, W, and Shimamura, A, on behalf of the North American Pediatric Aplastic Anemia Consortium. Diagnosis and Treatment of Pediatric Acquired Aplastic Anemia (AAA): an Initial Survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC). Pediatr Blood Cancer. 2014. 61(5):869-74. PMID: 24285674
Myers, KC, Bolyard, AA, Otto, B, Jones, A, Wong, TE, Harris, RE, Davies, SM, Dale, DC, Shimamura, A. Variable clinical presentation of Shwachman Diamond Syndrome: Update from the North American Shwachman Diamond Syndrome Registry. J Pediatr. 2014. 164(4):866-70. PMID: 24388329
Burroughs, LM, Nemecek, ER, Torgerson TR, Storer, BE, Talano J, Domm J, Giller RH, Shimamura A, Delaney C, Skoda-Smith S, Thakar MS, Baker KS, Rawlings DJ, Englund JA, Flowers ME, Deeg HJ, Storb R. Woolfrey AE. Treosulfan-Based Conditioning and Hematopoietic Cell Transplantation for Nonmalignant Diseases. Biol Blood Marrow Transplant. 2014. 20(12):1996-2003. PMID: 25196857
Ryan, TD, Jefferies, JL, Chin, C, Sticka, JJ, Taylor, MD, Harris, R, Moore, J, Goodridge, E, Mount, L, Bolyard, AA, Otto, B, Jones, A, Shimamura, A, Davies, S, and Myers, K. Abnormal Circumferential Strain Measured by Echocardiography is Present in Patients with Shwachman Diamond Syndrome Despite Normal Shortening Fraction. Pediatric Blood and Cancer. 2015. Jul;62(7):1228-31. PMID: 25732529
Steinberg-Shemer O, Keel S, Dgany O, Walsh T, Noy-Lotan S, Krasnov T, Yacobovich J, Quarello P, Ramenghi U, King MC, Shimamura A, Tamary H. Diamond-Blackfan Anemia: A Nonclassical Patient with Diangosis Assisted by Genomic Analysis. J. Pedatri Hematol Oncol. 2016 2016 Oct;38(7):e260-2. PMID: 27258031
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 uncharacterized phenotype of dyskeratosis ongenital and related telomere biology disorders. Eur Respir J. 2017 Jan 25;49(1). PMID: 27824607
Burroughs LM, Shimamura A, Talano JA, Domm J, Baker K, Delaney C, Frangoul H, Margolis D, Baker KS, Geddis A, Sandmaier BM, Deeg HJ, Storb R, Woolfrey AE. Allogeneic hematopoietic cell transplantation using treosulfan-based conditioning for treatment of marrow failure disorders. Biol Blood Marrow Transplant. 2017. 23(10):1669-1677. PMID: 28602958
Gansner JM, Achebe MM, Gray KJ, Yefidoff-Freedman R, Labovitis E, Parnes A, Connors JM, Connell NT, Discenza MN, Handin RI, Berliner N, Shimamura A, Ginsburg ES, Smith NA. Pregnancy outcomes in inherited bone marrow failure syndromes. Blood. 2017. 130(14):1671-1674. PMID: 28798157
Dale, DC, Bolyard AA, Marrero, T, Makaryan, V, Bonilla, MA, Link, DC, Newburger, P, Shimamura, A, Boxer, L., Spiekerman C. Long-term outcomes for patients with cyclic neutropenia treated with granulocyte colony-stimulating factor. New Engl J Med. 2017 377(23): 2290-2292. PMID: 29211670.
Rogers ZR, Nakano TA, Olson TS, Bertuch AA, Wang W, Gillio A, Coates TD, Chawla A, Castillo P, Kurre P, Gamper C, Bennett CM, Joshi S, Geddis AE, Boklan J, Nalepa G, Rothman JA, Huang JN, Kupfer GM, Cada M, Glader B, Walkovich KJ, Thompson AA, Hanna R, Vlachos A, Malsch M, Weller EA, Williams DA, Shimamura A. Immunosuppressive therapy for pediatric aplastic anemia: A North American Peditaric Aplastic Anemia Consortium Study. Haematologica. 2019. Apr 4. pii: haematol.2018.206540. doi: 10.3324/haematol.2018.206540. [Epub ahead of print] PMID: 30948484
Myers KC*, Furutani E*, Weller E, Siegele B, Galvin A, Arsenault V, Alter BP, Boulad F, Bueso-Ramos C, Burroughs L, Castillo P, Connelly J, Davies SM, DiNardo CD, Hanif I, Ho RH, Karras N, Manalang M, McReynolds LJ, Nakano TA, Nalepa G, Norkin M, Oberley MJ, Orgel E, Pastore YD, Rosenthal J, Walkovich K, Larson J, Malsch M, Elghetany MT, Fleming MD, Shimamura A. Clinical features and outcomes of patients with Shwachman Diamond Syndrome and myelodysplastic syndrome or acute myeloid leukaemia: a multicenter, retrospective cohort study. Lancet Haematol. 2020. 7(3): e238-e246. PMID: 31879230 *equal contribution
Furutani E, Shah AS, Zhao Y, Andorsky D, Dedeoglu F, Geddis A, Zhou Y, Libermann TA, Myers KC, Shimamura A. Inflammatory manifestations in patients with Shwachman-Diamond syndrome: a novel phenotype. Am J Med Genet. 2020 Apr 15. doi: 10.1002/ajmg.a.61593. PMID: 32293785
Pulsipher MA, Lehmann LE, Bertuch AA, Sasa G, Olson T, Nakano T, Gilio A, Burroughs LM, Lipton JM, Huang JN, Dickerson K, Bertaina A, Zhuang C, Malsch M, Fleming M, Weller E, Shimamura A, Williams DA. A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the North American Pediatric Aplastic Anemia Consortium and the Pediatric Transplantation and Cellular Therapy Consortium. Pediatr Blood Cancer. 2020 Oct;67(10):e28444. doi:10.1002/pbc.28444. Epub 2020 Aug 9. PMID: 32776425.
Nakano TA, Lau BW, Dickerson KE, Wlodarski M, Pollard J, Shimamura A, Hofmann I, Sasa G, Elghetany T, Cada M, Dror Y, Ding H, Allen SW, Hanna R, Campbell K, Olson TS. Diagnosis and treatment of pediatric myelodysplastic syndromes: A survey of the North American Pediatric Aplastic Anemia Consortium. Pediatr BloodCancer. 2020 Oct;67(10):e28652. doi: 10.1002/pbc.28652. Epub 2020 Aug 11. PMID: 32779892.
Case reports
1.Click ES, Cox B, Olson SB, Grompe M, Akkari Y, Moreau LA, Shimamura A, Sternen DL, Liu YJ, Leppig KA, Matthews DC, Parisi MA.Fanconi anemia-like presentation in an infant with constitutional deletion of 21q including the RUNX1 gene. Am J Med Genet A. 2011 Jul;155A(7):1673-9. PMID: 21626672 2.Singh, S, Vlachos, A, Morgenstern, NJ, Ouansafi, I, Ip, W, Rommens, J, Durie, P, Shimamura, A, Lipton, JM. Breast cancer in a case of Shwachman Diamond syndrome.Pediatr Blood Cancer. 2012 Nov;59(5):945-6. PMID: 22213587 3.Allenspach EJ, Bellodi C, Jeong D, Kopmar N, Nakamura T, Ochs HD, Ruggero D, Skoda-Smith S, Shimamura A, Torgerson TR. Common variable immunodeficiency as the initial presentation of dyskeratosis congenita. J Allergy Clin Immunol. 2013. 132(1):223-6. PMID: 23403051 4.Scott A, Glover J, Skoda-Smith S, Torgerson TR, Xu M, Burroughs LM, Woolfrey AE, Fleming MD, Shimamura A. Severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia.Pediatr. Blood Cancer. 2015. 62(11): 2047-2049. PMID 26011426 5. Gansner JM, Furutani E, Campagna DR, Fleming MD, Shimamura A. Pancreatic lipomatosis in Diamond-Blackfan anemia: The importance of genetic testing in bone marrow failure disorders. Am J Hematol. 2018 Sep;93(9):1194-1195. PMID: 29885000
Ruggero, D, and Shimamura, A. Marrow Failure: A Window into Ribosome Biology. Blood. 2014. 124(18):2784-2792. PMID: 25237201
Mamrak NE, Shimamura A, Howlett NG. Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia. Blood Rev. 2017 31(3):93-99.. PMID: 27760710
Shimamura, A. Aplastic anemia and clonal evolution: germline and somatic genetics. Hematology Am Soc Hematol Educ Program. 2016(1): 74-82. PMID: 27913465.
Furutani, E. and Shimamura, A. Germline Genetic Predisposition to Hematologic Malignancy. J. Clin Oncol. 2017 Mar 20;35(9):1018-1028. PMID: 28297620.
Hock, H. and Shimamura, A. ETV6 in hematopoiesis and leukemia predisposition. 2017. Semin Hematol. Apr;54(2):98-104. PMID: 28637624
Godley, L.A. and Shimamura, A. Genetic predisposition to hematologic malignancies: Management and surveillance. Jul 27;130(4):424-432. PMID: 28600339
Kennedy, AL. and Shimamura, A. Genetic predisposition to MDS: clinical features and clonal evolution. Blood. 2019 Mar7; 133(10):1071-1085. PMID: 30670445
Furutani, E. and Shimamura, A. Genetic predisposition to MDS: diagnosis and management. Hematology Am Soc. Hematol Educ Program. 2019 Dec 6;2019(1): 110-119. PMID: 31808839