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Michelle A Kelliher PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentMolecular, Cell and Cancer Biology
AddressUniversity of Massachusetts Medical School
364 Plantation Street, LRB
Worcester MA 01605
Phone508-856-8620
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentMicrobiology and Physiological Systems

    InstitutionUMMS - School of Medicine
    DepartmentMolecular, Cell and Cancer Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCancer Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentImmunology and Virology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program

    InstitutionUMMS - Programs, Centers and Institutes
    DepartmentCenter for AIDS Research


    Collapse Biography 
    Collapse education and training
    Smith College, Northampton, MA, United StatesBABiology
    Yale University, New Haven, CT, United StatesMSBiology
    Sackler School of Graduate Biomedical Sciences, Boston, MA, United StatesPHDImmunology
    Collapse awards and honors
    1995 - 1998Leukemia and Lymphoma Society Special Fellow Award
    2000 - 2002Sidney Kimmel Cancer Scholar Award
    2003 - 2008Leukemia and Lymphoma Society Scholar Award
    2008Leukemia and Lymphoma Society Stohlman Scholar Award
    2007Member, Leukemia and Lymphoma Society Career Development Review Panel
    2008 - 2012Permanent Member, NIH Cancer Genetics Study Section
    2012Reviewer, Charles A. King Trust Postdoctoral Fellowship Program
    2013 - 2015Hyundai Hope on Wheels Award for Pediatric Cancer
    2014Reviewer, Charles H. Hood Foundation

    Collapse Overview 
    Collapse overview


    Michelle Kelliher received her B.A. in Biology from Smith College and a M.S. degree in Biology from Yale University. She received her Ph.D. in Immunology from Tufts University Sackler School of Biomedical Sciences and completed her post-doctoral training in the Department of Genetics at Harvard Medical School. In 1998, Dr. Kelliher joined the UMMS Faculty and is currently a Professor in the Molecular, Cellular and Cancer Biology Department. Dr. Kelliher is a Scholar and Stohlman Scholar of the Leukemia and Lymphoma Society of America and a Sidney Kimmel Cancer Scholar.  Her research is supported by the NIH (NCI and NIAID), a Hyundai Hope Grant for Pediatric Cancers and an Alex’s Lemonade Stand Innovator Award.



    Visit the Kelliher Lab website: http://labs.umassmed.edu/kelliherlab/



    Mechanisms of Leukemogenesis



    Genetically engineered mouse model (GEMM) of pediatric T-ALL



    T cell acute lymphoblastic leukemia (T-ALL) is largely caused by the activation of TAL1, LMO1/2 and the NOTCH1 oncogenes. To model the disease in mice, we ectopically expressed the basic-helix-loop-helix (bHLH) transcription factor TAL1 and its binding partner LMO2 in developing mouse thymocytes. These transgenic mice develop T-ALL that resembles the human disease. We have shown that the DNA binding activity of TAL1 is not required to induce leukemia in mice and demonstrated that E2A or HEB heterozygosity accelerates TAL1-mediated disease (O’Neil et al., 2001; 2004).  These studies revealed that TAL1 transforms in part, by interfering with the E47/HEB bHLH heterodimer required for the expression of T cell differentiation genes (Figure?). In collaboration with the Look lab, we performed ChIP-seq analyses that demonstrated that TAL1 also participates in a TAL1-GATA3-RUNX1 autoregulatory loop that induces the expression of stem cell genes such as MYB in leukemia (Sanda et al., 2012).



    Identifying cooperating oncogenes



    We have used our GEMM and retroviral insertional mutagenesis (RIM) to identify genes that cooperate with TAL1 to cause leukemia in mice. The RIM screens revealed recurrent retroviral insertions in the Notch1, Myc and Ikaros loci (Sharma et al., 2006). Consistent with these data, NOTCH1 mutations were discovered in 54% of T-ALL patients and shown to develop spontaneously in our TAL1 transgenic mice (O’Neil et al., 2006). These mouse T-ALLs also express dominant-negative forms of Ikaros, indicating that Ikaros acts as a tumor suppressor in the disease. We then discovered that NOTCH1 contributes to leukemogenesis by directly regulating the expression of MYC (Sharma et al., 2006).





    NOTCH1-MYC axis mediates L-IC activity



    Leukemia-initiating cells (L-IC) are hypothesized to exhibit extensive proliferative and self-renewal capabilities and thereby mediate relapse. Using our GEMM of T-ALL, we identified the DN3 progenitor population as enriched in L-IC activity. Since NOTCH1 is important in thymic progenitor expansion, we hypothesized that the L-IC may depend on the NOTCH1-MYC pathway for their activity.  We found that treatment with a gamma-secretase inhibitor (GSI) which prevents NOTCH1 activation or the bromodomain 4 (BRD4) inhibitor JQ1, which targets MYC, significantly reduces or eliminates the L-IC population and prevents disease initiation (Tatarek et al., 2011; Roderick et al., 2014). These studies suggested that NOTCH and BRD4 inhibition may target the L-IC and prevent relapse.



    Establishing patient-derived xenografts from relapsed pediatric T-ALL and ETP-ALL patients



    To translate our findings to the human disease, we generated patient-derived xenografts (PDX) from pediatric T-ALL patients at the time of diagnosis and upon induction failure or relapse. We are using these models to study disease heterogeneity and to test the efficacy of combination targeted therapies. We found that GSI-JQ1 combination therapy was effective in vivo, significantly prolonging survival in PDX models of relapsed pediatric T-ALL (Knoechel et al., 2014).



    We are one of a few labs world wide that have also successfully generated PDX models from patients with early thymic progenitor (ETP)-ALL, a particularly treatment resistant ALL subtype. In collaboration with the Letai laboratory, we demonstrated that ETP-ALL is uniquely BCL2-dependent and highly sensitive to treatment in vivo with the BCL2 inhibitor ABT-199 (Chongaile et al., 2014). Our current goals are to examine human L-IC activity in these models and to optimize lentiviral-mediated transduction and CRISPR/Cas9 screening in primary human leukemic cells.



     



    RIP Kinases in Cell Death and Inflammation



    My laboratory has had a long-standing interest in RIP Kinases and their role in TNF- and TRIF-dependent signaling.  We demonstrated that a RIPK1 deficiency in the mouse results in neonatal lethality due to extensive TNF-induced cell death and inflammation (Kelliher et al., 1998; Cusson et al 2002). We showed that RIPK1 is recruited to the TNF receptor 1 (Tnfr1) and the Toll-like receptors (TLR) 3 and 4 via the adapter TRIF and is stably ubiquitin-modified with K63-linked polyubiquitin chains (Meylan et al., 2004; Lee et al., 2004). We have since established that in addition to TNF-induced apoptosis, RIPK1 regulates a form of programmed necrosis called necroptosis. Necroptosis is thought to require the kinase activities of RIPK1, RIPK3 and MLKL (Figure?) and induces an inflammatory form of cell death. We provide genetic evidence that in the absence of RIPK1, tissues undergo apoptosis and RIPK3-mediated necroptosis. Unlike Ripk1-/- or Ripk1-/-Tnfr1-/- mice, which die during the postnatal period, Ripk1/Tnfr1/Ripk3 triple knock out mice survive to adulthood (Dillon et al., 2014). These in vivo studies demonstrate that RIPK1 is a master regulator of cell death and inflammation.



     



    To identify the cell types and tissues that depend on RIPK1 for survival, we developed Ripk1 conditional mice and RIPK1 kinase inactive (D138N) mice.  These mouse models allow us to examine the role of RIPK1 in tissue homeostasis and inflammation. Our published work demonstrates critical survival roles for RIPK1 in the intestinal epithelium, keratinocytes and cells of the hematopoietic lineage (Dannappel, et al., 2014;Roderick et al., 2014). We also demonstrated that RIPK1D138N mice are completely protected from TNF-induced hypothermia and shock in vivo (Polykratis et al., 2014).  These studies indicate that RIP kinase-dependent necroptotic death mediates shock and may contribute to sepsis, raising the possibility that RIPK inhibitors may have clinical utility in these patients and in chronic inflammatory disease.



    Collapse Rotation Projects


    Please visit the Kelliher Lab website at: http://labs.umassmed.edu/kelliherlab/ to learn more about our current research areas.



     



    1. Identify genes/pathways that mediate leukemia-initiating cell survival



     



    2. Understand the molecular basis of glucocorticoid resistance in leukemia



     



    3. Examine contribution of RIPK1 kinase in inflammatory and autoimmune disease mouse models.



     



    4.  Reveal tissue-specific roles for RIPK1 in cell death and inflammation. Use conditional Ripk1 allele to investigate effects of Ripk1       deletion in liver, pancreas and antigen presenting cells.



     



    Collapse Post Docs

    A postdoctoral position is available to study in this laboratory. Contact Dr. Kelliher for additional details.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Delgado-Martin C, Meyer LK, Huang BJ, Shimano KA, Zinter MS, Nguyen JV, Smith GA, Taunton J, Winter SS, Roderick JR, Kelliher MA, Horton TM, Wood BL, Teachey D, Hermiston ML. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia. 2017 May 09. PMID: 28484265.
      View in: PubMed
    2. Saleh D, Najjar M, Zelic M, Shah S, Nogusa S, Polykratis A, Paczosa MK, Gough PJ, Bertin J, Whalen M, Fitzgerald KA, Slavov N, Pasparakis M, Balachandran S, Kelliher M, Mecsas J, Degterev A. Kinase Activities of RIPK1 and RIPK3 Can Direct IFN-ß Synthesis Induced by Lipopolysaccharide. J Immunol. 2017 Jun 01; 198(11):4435-4447. PMID: 28461567.
      View in: PubMed
    3. Carr MI, Roderick JE, Zhang H, Woda BA, Kelliher MA, Jones SN. Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice. Proc Natl Acad Sci U S A. 2016 Dec 27; 113(52):15024-15029. PMID: 27956626.
      View in: PubMed
    4. Lian H, Li D, Zhou Y, Landesman-Bollag E, Zhang G, Anderson NM, Tang KC, Roderick JE, Kelliher MA, Seldin DC, Fu H, Feng H. CK2 inhibitor CX-4945 destabilizes NOTCH1 and synergizes with JQ1 against human T-acute lymphoblastic leukemic cells. Haematologica. 2017 Jan; 102(1):e17-e21. PMID: 27758824.
      View in: PubMed
    5. Carr MI, Roderick JE, Gannon HS, Kelliher MA, Jones SN. Mdm2 Phosphorylation Regulates Its Stability and Has Contrasting Effects on Oncogene and Radiation-Induced Tumorigenesis. Cell Rep. 2016 Sep 6; 16(10):2618-29. PMID: 27568562.
      View in: PubMed
    6. Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekofer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LeBoeuf NR, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 Jul 11; 30(1):183. PMID: 27479034.
      View in: PubMed
    7. Legarda D, Justus SJ, Ang RL, Rikhi N, Li W, Moran TM, Zhang J, Mizoguchi E, Zelic M, Kelliher MA, Blander JM, Ting AT. CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN. Cell Rep. 2016 Jun 14; 15(11):2449-61. PMID: 27264187.
      View in: PubMed
    8. Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekoffer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LaBoeuf N, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 Apr 11; 29(4):574-86. PMID: 27070704.
      View in: PubMed
    9. Vlantis K, Wullaert A, Polykratis A, Kondylis V, Dannappel M, Schwarzer R, Welz P, Corona T, Walczak H, Weih F, Klein U, Kelliher M, Pasparakis M. NEMO Prevents RIP Kinase 1-Mediated Epithelial Cell Death and Chronic Intestinal Inflammation by NF-?B-Dependent and -Independent Functions. Immunity. 2016 Mar 15; 44(3):553-67. PMID: 26982364.
      View in: PubMed
    10. Anderson NM, Li D, Peng HL, Laroche FJ, Mansour MR, Gjini E, Aioub M, Helman DJ, Roderick JE, Cheng T, Harrold I, Samaha Y, Meng L, Amsterdam A, Neuberg DS, Denton TT, Sanda T, Kelliher MA, Singh A, Look AT, Feng H. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. Leukemia. 2016 Jun; 30(6):1365-74. PMID: 26876595.
      View in: PubMed
    11. Ma L, Roderick J, Kelliher MA, Green MR. High-Throughput Screening of Tyrosine Kinase Inhibitor Resistant Genes in CML. Methods Mol Biol. 2016; 1465:159-73. PMID: 27581147.
      View in: PubMed
    12. Kondylis V, Polykratis A, Ehlken H, Ochoa-Callejero L, Straub BK, Krishna-Subramanian S, Van TM, Curth HM, Heise N, Weih F, Klein U, Schirmacher P, Kelliher M, Pasparakis M. NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis. Cancer Cell. 2015 Nov 09; 28(5):582-98. PMID: 26555174.
      View in: PubMed
    13. El-Assaad W, El-Kouhen K, Mohammad AH, Yang J, Morita M, Gamache I, Mamer O, Avizonis D, Hermance N, Kersten S, Tremblay ML, Kelliher MA, Teodoro JG. Deletion of the gene encoding G0/G 1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice. Diabetologia. 2015 Jan; 58(1):149-57. PMID: 25381555.
      View in: PubMed
    14. Roderick JE, Hermance N, Zelic M, Simmons MJ, Polykratis A, Pasparakis M, Kelliher MA. Hematopoietic RIPK1 deficiency results in bone marrow failure caused by apoptosis and RIPK3-mediated necroptosis. Proc Natl Acad Sci U S A. 2014 Oct 7; 111(40):14436-41. PMID: 25246544.
      View in: PubMed
    15. Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, Eftychi C, Lin J, Corona T, Hermance N, Zelic M, Kirsch P, Basic M, Bleich A, Kelliher M, Pasparakis M. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature. 2014 Sep 04; 513(7516):90-4. PMID: 25132550.
      View in: PubMed
    16. Wolfe AL, Singh K, Zhong Y, Drewe P, Rajasekhar VK, Sanghvi VR, Mavrakis KJ, Jiang M, Roderick JE, Van der Meulen J, Schatz JH, Rodrigo CM, Zhao C, Rondou P, de Stanchina E, Teruya-Feldstein J, Kelliher MA, Speleman F, Porco JA, Pelletier J, Rätsch G, Wendel HG. RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer. Nature. 2014 Sep 4; 513(7516):65-70. PMID: 25079319.
      View in: PubMed
    17. Polykratis A, Hermance N, Zelic M, Roderick J, Kim C, Van TM, Lee TH, Chan FK, Pasparakis M, Kelliher MA. Cutting edge: RIPK1 Kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J Immunol. 2014 Aug 15; 193(4):1539-43. PMID: 25015821.
      View in: PubMed
    18. Chonghaile TN, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, Loh ML, Hunger SP, Wood B, DeAngelo DJ, Stone R, Harris M, Gutierrez A, Kelliher MA, Letai A. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov. 2014 Sep; 4(9):1074-87. PMID: 24994123.
      View in: PubMed
    19. Dillon CP, Weinlich R, Rodriguez DA, Cripps JG, Quarato G, Gurung P, Verbist KC, Brewer TL, Llambi F, Gong YN, Janke LJ, Kelliher MA, Kanneganti TD, Green DR. RIPK1 blocks early postnatal lethality mediated by caspase-8 and RIPK3. Cell. 2014 May 22; 157(5):1189-202. PMID: 24813850.
      View in: PubMed
    20. Weng D, Marty-Roix R, Ganesan S, Proulx MK, Vladimer GI, Kaiser WJ, Mocarski ES, Pouliot K, Chan FK, Kelliher MA, Harris PA, Bertin J, Gough PJ, Shayakhmetov DM, Goguen JD, Fitzgerald KA, Silverman N, Lien E. Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. Proc Natl Acad Sci U S A. 2014 May 20; 111(20):7391-6. PMID: 24799678.
      View in: PubMed
    21. Gutierrez A, Roderick JE, Kelliher MA. Leukemia propagating cells Akt up. Cancer Cell. 2014 Mar 17; 25(3):263-5. PMID: 24651006.
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    22. Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet. 2014 Apr; 46(4):364-70. PMID: 24584072.
      View in: PubMed
    23. Reynolds C, Roderick JE, LaBelle JL, Bird G, Mathieu R, Bodaar K, Colon D, Pyati U, Stevenson KE, Qi J, Harris M, Silverman LB, Sallan SE, Bradner JE, Neuberg DS, Look AT, Walensky LD, Kelliher MA, Gutierrez A. Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia. Leukemia. 2014 Sep; 28(9):1819-27. PMID: 24552990.
      View in: PubMed
    24. Roderick JE, Tesell J, Shultz LD, Brehm MA, Greiner DL, Harris MH, Silverman LB, Sallan SE, Gutierrez A, Look AT, Qi J, Bradner JE, Kelliher MA. c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood. 2014 Feb 13; 123(7):1040-50. PMID: 24394663.
      View in: PubMed
    25. Mavrogiorgos N, Mekasha S, Yang Y, Kelliher MA, Ingalls RR. Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune response. Innate Immun. 2014 May; 20(4):377-89. PMID: 23884094.
      View in: PubMed
    26. Mansour MR, Sanda T, Lawton LN, Li X, Kreslavsky T, Novina CD, Brand M, Gutierrez A, Kelliher MA, Jamieson CH, von Boehmer H, Young RA, Look AT. The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia. J Exp Med. 2013 Jul 29; 210(8):1545-57. PMID: 23857984.
      View in: PubMed
    27. Lukens JR, Vogel P, Johnson GR, Kelliher MA, Iwakura Y, Lamkanfi M, Kanneganti TD. RIP1-driven autoinflammation targets IL-1a independently of inflammasomes and RIP3. Nature. 2013 Jun 13; 498(7453):224-7. PMID: 23708968.
      View in: PubMed
    28. Sanda T, Tyner JW, Gutierrez A, Ngo VN, Glover J, Chang BH, Yost A, Ma W, Fleischman AG, Zhou W, Yang Y, Kleppe M, Ahn Y, Tatarek J, Kelliher MA, Neuberg DS, Levine RL, Moriggl R, Müller M, Gray NS, Jamieson CH, Weng AP, Staudt LM, Druker BJ, Look AT. TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer Discov. 2013 May; 3(5):564-77. PMID: 23471820.
      View in: PubMed
    29. Sawai CM, Freund J, Oh P, Ndiaye-Lobry D, Bretz JC, Strikoudis A, Genesca L, Trimarchi T, Kelliher MA, Clark M, Soulier J, Chen-Kiang S, Aifantis I. Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia. Cancer Cell. 2012 Oct 16; 22(4):452-65. PMID: 23079656.
      View in: PubMed
    30. Simmons MJ, Serra R, Hermance N, Kelliher MA. NOTCH1 inhibition in vivo results in mammary tumor regression and reduced mammary tumorsphere-forming activity in vitro. Breast Cancer Res. 2012 Sep 19; 14(5):R126. PMID: 22992387.
      View in: PubMed
    31. Sanda T, Lawton LN, Barrasa MI, Fan ZP, Kohlhammer H, Gutierrez A, Ma W, Tatarek J, Ahn Y, Kelliher MA, Jamieson CH, Staudt LM, Young RA, Look AT. Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia. Cancer Cell. 2012 Aug 14; 22(2):209-21. PMID: 22897851.
      View in: PubMed
    32. Fortes GB, Alves LS, de Oliveira R, Dutra FF, Rodrigues D, Fernandez PL, Souto-Padron T, De Rosa MJ, Kelliher M, Golenbock D, Chan FK, Bozza MT. Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production. Blood. 2012 Mar 8; 119(10):2368-75. PMID: 22262768.
      View in: PubMed
    33. Tatarek J, Cullion K, Ashworth T, Gerstein R, Aster JC, Kelliher MA. Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL. Blood. 2011 Aug 11; 118(6):1579-90. PMID: 21670468.
      View in: PubMed
    34. Yang Y, Xia F, Hermance N, Mabb A, Simonson S, Morrissey S, Gandhi P, Munson M, Miyamoto S, Kelliher MA. A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. Mol Cell Biol. 2011 Jul; 31(14):2774-86. PMID: 21606198.
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    35. Draheim KM, Hermance N, Yang Y, Arous E, Calvo J, Kelliher MA. A DNA-binding mutant of TAL1 cooperates with LMO2 to cause T cell leukemia in mice. Oncogene. 2011 Mar 10; 30(10):1252-60. PMID: 21057528.
      View in: PubMed
    36. De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink JP, Cordon-Cardo C, Califano A, Ferrando AA. The TLX1 oncogene drives aneuploidy in T cell transformation. Nat Med. 2010 Nov; 16(11):1321-7. PMID: 20972433.
      View in: PubMed
    37. Ashworth TD, Pear WS, Chiang MY, Blacklow SC, Mastio J, Xu L, Kelliher M, Kastner P, Chan S, Aster JC. Deletion-based mechanisms of Notch1 activation in T-ALL: key roles for RAG recombinase and a conserved internal translational start site in Notch1. Blood. 2010 Dec 16; 116(25):5455-64. PMID: 20852131.
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    38. Coulombe F, Divangahi M, Veyrier F, de Léséleuc L, Gleason JL, Yang Y, Kelliher MA, Pandey AK, Sassetti CM, Reed MB, Behr MA. Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J Exp Med. 2009 Aug 3; 206(8):1709-16. PMID: 19581406.
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    39. Pandey AK, Yang Y, Jiang Z, Fortune SM, Coulombe F, Behr MA, Fitzgerald KA, Sassetti CM, Kelliher MA. NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog. 2009 Jul; 5(7):e1000500. PMID: 19578435.
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    40. Cullion K, Draheim KM, Hermance N, Tammam J, Sharma VM, Ware C, Nikov G, Krishnamoorthy V, Majumder PK, Kelliher MA. Targeting the Notch1 and mTOR pathways in a mouse T-ALL model. Blood. 2009 Jun 11; 113(24):6172-81. PMID: 19246562.
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    41. Ramnarain DB, Paulmurugan R, Park S, Mickey BE, Asaithamby A, Saha D, Kelliher MA, Mukhopadhyay P, Banani F, Madden CJ, Wright PS, Chakravarty S, Habib AA. RIP1 links inflammatory and growth factor signaling pathways by regulating expression of the EGFR. Cell Death Differ. 2008 Feb; 15(2):344-53. PMID: 18007664.
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    42. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher MA. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007 Dec 14; 282(50):36223-9. PMID: 17947236.
      View in: PubMed
    43. Abbott DW, Yang Y, Hutti JE, Madhavarapu S, Kelliher MA, Cantley LC. Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains. Mol Cell Biol. 2007 Sep; 27(17):6012-25. PMID: 17562858.
      View in: PubMed
    44. Sharma VM, Draheim KM, Kelliher MA. The Notch1/c-Myc pathway in T cell leukemia. Cell Cycle. 2007 Apr 15; 6(8):927-30. PMID: 17404512.
      View in: PubMed
    45. Huye LE, Ning S, Kelliher M, Pagano JS. Interferon regulatory factor 7 is activated by a viral oncoprotein through RIP-dependent ubiquitination. Mol Cell Biol. 2007 Apr; 27(8):2910-8. PMID: 17296724.
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    46. Sharma VM, Calvo JA, Draheim KM, Cunningham LA, Hermance N, Beverly L, Krishnamoorthy V, Bhasin M, Capobianco AJ, Kelliher MA. Notch1 contributes to mouse T-cell leukemia by directly inducing the expression of c-myc. Mol Cell Biol. 2006 Nov; 26(21):8022-31. PMID: 16954387.
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    47. Chang PY, Draheim K, Kelliher MA, Miyamoto S. NFKB1 is a direct target of the TAL1 oncoprotein in human T leukemia cells. Cancer Res. 2006 Jun 15; 66(12):6008-13. PMID: 16778171.
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    48. Shank-Calvo JA, Draheim K, Bhasin M, Kelliher MA. p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice. Oncogene. 2006 May 18; 25(21):3023-31. PMID: 16407836.
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    49. O'Neil J, Calvo J, McKenna K, Krishnamoorthy V, Aster JC, Bassing CH, Alt FW, Kelliher M, Look AT. Activating Notch1 mutations in mouse models of T-ALL. Blood. 2006 Jan 15; 107(2):781-5. PMID: 16166587.
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    50. Cusson-Hermance N, Khurana S, Lee TH, Fitzgerald KA, Kelliher MA. Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem. 2005 Nov 4; 280(44):36560-6. PMID: 16115877.
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    51. Das S, Cho J, Lambertz I, Kelliher MA, Eliopoulos AG, Du K, Tsichlis PN. Tpl2/cot signals activate ERK, JNK, and NF-kappaB in a cell-type and stimulus-specific manner. J Biol Chem. 2005 Jun 24; 280(25):23748-57. PMID: 15833743.
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    52. Vivarelli MS, McDonald D, Miller M, Cusson N, Kelliher M, Geha RS. RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation. J Exp Med. 2004 Aug 2; 200(3):399-404. PMID: 15280422.
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    53. O'Neil J, Shank J, Cusson N, Murre C, Kelliher M. TAL1/SCL induces leukemia by inhibiting the transcriptional activity of E47/HEB. Cancer Cell. 2004 Jun; 5(6):587-96. PMID: 15193261.
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    54. Lee TH, Shank J, Cusson N, Kelliher MA. The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J Biol Chem. 2004 Aug 6; 279(32):33185-91. PMID: 15175328.
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    55. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol. 2004 May; 5(5):503-7. PMID: 15064760.
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    56. Lee TH, Huang Q, Oikemus S, Shank J, Ventura JJ, Cusson N, Vaillancourt RR, Su B, Davis RJ, Kelliher MA. The death domain kinase RIP1 is essential for tumor necrosis factor alpha signaling to p38 mitogen-activated protein kinase. Mol Cell Biol. 2003 Nov; 23(22):8377-85. PMID: 14585994.
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    57. O'Neil J, Ventura JJ, Cusson N, Kelliher M. NF-kappaB activation in premalignant mouse tal-1/scl thymocytes and tumors. Blood. 2003 Oct 1; 102(7):2593-6. PMID: 12816868.
      View in: PubMed
    58. Cusson N, Oikemus S, Kilpatrick ED, Cunningham L, Kelliher M. The death domain kinase RIP protects thymocytes from tumor necrosis factor receptor type 2-induced cell death. J Exp Med. 2002 Jul 1; 196(1):15-26. PMID: 12093867.
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    59. O'Neil J, Billa M, Oikemus S, Kelliher M. The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice. Oncogene. 2001 Jun 28; 20(29):3897-905. PMID: 11439353.
      View in: PubMed
    60. Lin Y, Devin A, Cook A, Keane MM, Kelliher M, Lipkowitz S, Liu ZG. The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of IkappaB kinase and c-Jun N-terminal kinase. Mol Cell Biol. 2000 Sep; 20(18):6638-45. PMID: 10958661.
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    61. Devin A, Cook A, Lin Y, Rodriguez Y, Kelliher M, Liu Z. The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Immunity. 2000 Apr; 12(4):419-29. PMID: 10795740.
      View in: PubMed
    62. Smith D, Shang F, Nowell TR, Asmundsson G, Perrone G, Dallal G, Scott L, Kelliher M, Gindelsky B, Taylor A. Decreasing ascorbate intake does not affect the levels of glutathione, tocopherol or retinol in the ascorbate-requiring osteogenic disorder shionogi rats. J Nutr. 1999 Jun; 129(6):1229-32. PMID: 10356092.
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    63. Scrofano MM, Shang F, Nowell TR, Gong X, Smith DE, Kelliher M, Dunning J, Mura CV, Taylor A. Calorie restriction, stress and the ubiquitin-dependent pathway in mouse livers. Mech Ageing Dev. 1998 Nov 16; 105(3):273-90. PMID: 9862235.
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    64. Scrofano MM, Shang F, Nowell TR, Gong X, Smith DE, Kelliher M, Dunning J, Mura CV, Taylor A. Aging, calorie restriction and ubiquitin-dependent proteolysis in the livers of Emory mice. Mech Ageing Dev. 1998 Apr 1; 101(3):277-96. PMID: 9622231.
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    65. Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ, Leder P. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity. 1998 Mar; 8(3):297-303. PMID: 9529147.
      View in: PubMed
    66. Kelliher MA, Seldin DC, Leder P. Tal-1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha. EMBO J. 1996 Oct 1; 15(19):5160-6. PMID: 8895560.
      View in: PubMed
    67. Kelliher MA, Weckstein DJ, Knott AG, Wortis HH, Rosenberg N. ABL oncogenes directly stimulate two distinct target cells in bone marrow from 5-fluorouracil-treated mice. Oncogene. 1993 May; 8(5):1249-56. PMID: 8479746.
      View in: PubMed
    68. Kelliher M, Knott A, McLaughlin J, Witte ON, Rosenberg N. Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. Mol Cell Biol. 1991 Sep; 11(9):4710-6. PMID: 1875948.
      View in: PubMed
    69. Kelliher MA, McLaughlin J, Witte ON, Rosenberg N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci U S A. 1990 Sep; 87(17):6649-53. PMID: 2204061.
      View in: PubMed
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