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Research and Clinical Interests

Our laboratory studies the molecular mechanisms controlling hematopoietic stem cell (HSC) self-renewal, differentiation and transformation. More specifically we focus on the regulation of HSC cell cycle entry and on the effects of Notch signaling in stem cell differentiation. Finally, we study the role of the Notch pathway as an oncogenic trigger in acute lymphoblastic leukemia. Our goal is to design novel therapies that will target and suppress Notch transforming activity in vivo.

Selected Publications

Reavie L, Gatta GD, Crusio K, Aranda-Orgilles B, Buckley SM, Thompson B, Lee E, Gao J, Bredemeyer AL, Helmink BA, Zavadil J, Sleckman BP, Palomero T, Ferrando A, Aifantis I. Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase–substrate complex. Nat Immunol. 2010 Jan;Epub 2010 Jan 17. Cited in Pubmed; PMID 20081848. doi: 10.1038/ni.1839.

Buonamici S, Trimarchi T, Ruocco MG, Reavie L, Cathelin S, Mar BG, Klinakis A, Lukyanov Y, Tseng JC, Sen F, Gehrie E, Li M, Newcomb E, Zavadil J, Meruelo D, Lipp M, Ibrahim S, Efstratiadis A, Zagzag D, Bromberg JS, Dustin ML, Aifantis I. CCR7 signaling as an essential regulator of CNS infiltration in T cell leukemia. Nature. 2009 Jun 18;459(7249):1000-4. Cited in Pubmed; PMID 19536265. doi: 10.1038/nature08020.

Gao J, Graves S, Koch U, Liu S, Jankovic V, Buonamici S, El Andaloussi A, Nimer SD, Kee BL, Taichman R, Radtke F, Aifantis I. Hedgehog Signaling Is Dispensable for Adult Hematopoietic Stem Cell Function. Cell Stem Cell. 2009 Jun 5;4(6):548-58. Cited in Pubmed; PMID 19497283. doi: 10.1016/j.stem.2009.03.015.

Mandal M, Crusio KM, Meng F, Liu S, Kinsella M, Clark MR, Takeuchi O, Aifantis I. Regulation of lymphocyte progenitor survival by the proapoptotic activities of Bim and Bid. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20840-5. Epub 2008 Dec 16. Cited in Pubmed; PMID 19088189. doi: 10.1073/pnas.0807557106. PMCID: PMC2634950.

Thompson BJ, Jankovic V, Gao J, Buonamici S, Vest A, Lee JM, Zavadil J, Nimer SD, Aifantis, I. Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7. J Exp Med. 2008 May;Epub 2008 May 12. Cited in Pubmed; PMID 18474632. doi: 10.1084/jem.20080277. PMCID: PMC2413036.

Buonamici S, Raetz E, Aifantis I. Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat Rev Immunol. 2008 Apr;Epub 2008 Apr 18. Cited in Pubmed; PMID 18421304. doi: 10.1038/nri2304.

Johnson K, Hashimshony T, Sawai CM, Pongubala JM, Skok JA, Aifantis I, Singh H. Regulation of Immunoglobulin Light-Chain Recombination by the Transcription Factor IRF-4 and the Attenuation of Interleukin-7 Signaling. Immunity. 2008 Mar;28(3):335-45. Epub 2008 Feb 14. Cited in Pubmed; PMID 18280186. doi: 10.1016/j.immuni.2007.12.019.

Thompson B*, Buonamici S*, Sulis M-L, Palomero T, Vilimas T, Basso G, Ferrando A, Aifantis I. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med. 2007 Aug 6;204(8):1825-35. Cited in Pubmed; PMID 17646408. doi: 10.1084/jem.20070872. PMCID: PMC2118676.

Vilimas T*, Mascarenhas J*, Palomero T, Mandal M, Buonamici S, Ferrando A, Miele L, Aifantis I. Targeting the NF-kB signaling pathway in Notch1-induced T cell leukemia. Nat Med. 2007 Jan;13(1):70-77. Cited in Pubmed; PMID 17173050. doi: 10.1038/nm1524.

Scimone ML, Aifantis I, Apostolou I, von Boehmer H, von Andrian UH. A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus. Proc Natl Acad Sci U S A. 2006 May 2;103(18):7006-11. Epub 2006 Apr 25. Cited in Pubmed; PMID 16641096. doi: 10.1073/pnas.0602024103. PMCID: PMC1459009.

Cooper A, Sawai K, Powers S, Sicinska E, Sicinski P, Clark M, Aifantis I. A unique function for cyclin D3 in early B cell development. Nat Immunol. 2006; 7:489-497. Cited in Pubmed; PMID 16582912.

Aifantis I, Bassing C, Garbe A, Sawai K, Alt F, von Boehmer H. The Eδ enhancer controls the generation of DN αβ-TCR expressing T cells that can give rise to different lineages of αβ T cells. J Exp Med. 2006;203(6):1543-50. Cited in Pubmed; PMID 16754716.

El Andaloussi A, Graves S, Meng F, Mashayekhi M, Aifantis I. The Hedgehog signaling network controls lymphoid progenitor differentiation in the thymus. Nat Immunol. 2006;7(4):418-426. Cited in Pubmed; PMID 16518394.

Mandal M, Borowski C, Palomero T, Ferrando AA, Oberdoerffer P, Meng F, Ruiz-Vela A, Ciofani M, Zuniga-Pflucker JC, Screpanti I, Look AT, Korsmeyer SJ, Rajewsky K, von Boehmer H, Aifantis I. The BCL2A1 gene, as a pre-TCR-induced regulator of thymocyte survival and T cell leukemia. J Exp Med. 2005 Feb 21;201(4):603–14. Cited in Pubmed; PMID 15728238.

Martin CH*, Aifantis I*, Scimone ML, von Andrian UH, Reizis B, von Boehmer H, Gounari F. B220+, CD19- precursors represent a missing link between bone marrow and intra-thymic lymphoid committed progenitors. Nat Immunol. 2003;4:866-873. Cited in Pubmed; PMID 12925850.

Selected Books and Reviews

Aifantis I, Sawai C. Energy addiction and lymphocyte differentiation: a new role for the liver kinase B1 kinase. Eur J Immunol. 2010 Jan;40(1):19-21. Cited in Pubmed; PMID 20017195. doi: 10.1002/eji.200940206.

Gao J, Aifantis I. Hedgehog and hematopoietic stem cell differentiation: don't believe the hype!. Cell Cycle. 2009 Dec;8(23):3789-90. Cited in Pubmed; PMID 19934654.

Clark MR, Cooper AB, Wang L, Aifantis I. The Pre-B cell receptor in B cell development: Recent advances, persistent questions and conserved mechanisms. In: Grosschedl R, Singh H, editors. Molecular Analysis of B-Lymphocyte Development. Berlin: Springer Verlag; 2005. pp. 87–104.