Utpal Dave
Faculty Member
Last active: 2/22/2016

Profile

My lab is interested in the oncogenic pathways that are deregulated in human T-cell neoplasms. These cancers can be divided based on the cell of origin into immature, T-cell acute lymphoblastic leukemias (T-ALL) and mature, peripheral T-cell Non-Hodgkin lymphomas. In T-ALL, we are focused on understanding the function of the LIM-domain-Only-2 (LMO2) gene which is deregulated in the majority of patients. Mouse knockout studies show that Lmo2 is required for the maintenance of the hematopoietic stem cells. We hypothesize that the pathways Lmo2 regulates in stem cells may also be induced in Lmo2-associated leukemias. Experiments are ongoing to explore this idea.


Our other projects address the mechanism of mature T-cell transformation by studying HTLV-1-induced disease. HTLV-1 is a complex retrovirus that induces leukemia or lymphoma in only 5% of infected carriers after a long latency of 30-50 years. This long latency in the setting of lifelong viremia is reminiscent of the slow transforming murine leukemia viruses that we are studying in mice. Likewise, we hypothesize that insertional mutagenesis may be an active mechanism of disease induction for HTLV-1. Another project involves the role of the IL-2/IL2RG pathway in leukemia induction. We hypothesize that gain of function mutations may be occurring in genes in this pathway as tumor progression events.

Our studies will shed light on the pathogenesis of T-cell neoplasms and may provide novel targets for diagnosis or therapy.






Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation. Triplett TA, Cardenas KT, Lancaster JN, Hu Z, Selden HJ, Jasso GJ, Balasubramanyam S, Chan K, Li L, Chen X, Marcogliese AN, Davé UP, Love PE, Ehrlich LI (2016) Proc Natl Acad Sci U S A 113(8): E1016-25
    › Primary publication · 26862168 (PubMed) · PMC4776467 (PubMed Central)
  2. LMO2 Oncoprotein Stability in T-Cell Leukemia Requires Direct LDB1 Binding. Layer JH, Alford CE, McDonald WH, Davé UP (2016) Mol Cell Biol 36(3): 488-506
    › Primary publication · 26598604 (PubMed) · PMC4719424 (PubMed Central)
  3. Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides. McGirt LY, Jia P, Baerenwald DA, Duszynski RJ, Dahlman KB, Zic JA, Zwerner JP, Hucks D, Dave U, Zhao Z, Eischen CM (2015) Blood 126(4): 508-19
    › Primary publication · 26082451 (PubMed) · PMC4513251 (PubMed Central)
  4. Hhex is Required at Multiple Stages of Adult Hematopoietic Stem and Progenitor Cell Differentiation. Goodings C, Smith E, Mathias E, Elliott N, Cleveland SM, Tripathi RM, Layer JH, Chen X, Guo Y, Shyr Y, Hamid R, Du Y, Davé UP (2015) Stem Cells 33(8): 2628-41
    › Primary publication · 25968920 (PubMed) · PMC4641572 (PubMed Central)
  5. Enforced expression of E47 has differential effects on Lmo2-induced T-cell leukemias. Goodings C, Tripathi R, Cleveland SM, Elliott N, Guo Y, Shyr Y, Davé UP (2015) Leuk Res 39(1): 100-9
    › Primary publication · 25499232 (PubMed) · PMC4277943 (PubMed Central)
  6. LMO2 induces T-cell leukemia with epigenetic deregulation of CD4. Cleveland SM, Goodings C, Tripathi RM, Elliott N, Thompson MA, Guo Y, Shyr Y, Davé UP (2014) Exp Hematol 42(7): 581-93.e5
    › Primary publication · 24792354 (PubMed) · PMC4241760 (PubMed Central)
  7. LIM domain only-2 (LMO2) induces T-cell leukemia by two distinct pathways. Smith S, Tripathi R, Goodings C, Cleveland S, Mathias E, Hardaway JA, Elliott N, Yi Y, Chen X, Downing J, Mullighan C, Swing DA, Tessarollo L, Li L, Love P, Jenkins NA, Copeland NG, Thompson MA, Du Y, Davé UP (2014) PLoS One 9(1): e85883
    › Primary publication · 24465765 (PubMed) · PMC3897537 (PubMed Central)
  8. Tgif1 regulates quiescence and self-renewal of hematopoietic stem cells. Yan L, Womack B, Wotton D, Guo Y, Shyr Y, Davé U, Li C, Hiebert S, Brandt S, Hamid R (2013) Mol Cell Biol 33(24): 4824-33
    › Primary publication · 24100014 (PubMed) · PMC3889555 (PubMed Central)
  9. Lmo2 induces hematopoietic stem cell-like features in T-cell progenitor cells prior to leukemia. Cleveland SM, Smith S, Tripathi R, Mathias EM, Goodings C, Elliott N, Peng D, El-Rifai W, Yi D, Chen X, Li L, Mullighan C, Downing JR, Love P, Davé UP (2013) Stem Cells 31(5): 882-94
    › Primary publication · 23378057 (PubMed) · PMC3652616 (PubMed Central)
  10. Targeting nonclassical oncogenes for therapy in T-ALL. Subramaniam PS, Whye DW, Efimenko E, Chen J, Tosello V, De Keersmaecker K, Kashishian A, Thompson MA, Castillo M, Cordon-Cardo C, Davé UP, Ferrando A, Lannutti BJ, Diacovo TG (2012) Cancer Cell 21(4): 459-72
    › Primary publication · 22516257 (PubMed)
  11. Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm. Chmielecki J, Peifer M, Viale A, Hutchinson K, Giltnane J, Socci ND, Hollis CJ, Dean RS, Yenamandra A, Jagasia M, Kim AS, Davé UP, Thomas RK, Pao W (2012) Genes Chromosomes Cancer 51(1): 54-65
    › Primary publication · 21938754 (PubMed)
  12. Sox4 cooperates with PU.1 haploinsufficiency in murine myeloid leukemia. Aue G, Du Y, Cleveland SM, Smith SB, Davé UP, Liu D, Weniger MA, Metais JY, Jenkins NA, Copeland NG, Dunbar CE (2011) Blood 118(17): 4674-81
    › Primary publication · 21878674 (PubMed) · PMC3208283 (PubMed Central)
  13. FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma. Elliott NE, Cleveland SM, Grann V, Janik J, Waldmann TA, Davé UP (2011) Blood 118(14): 3911-21
    › Primary publication · 21821710 (PubMed) · PMC3193267 (PubMed Central)
  14. A role for proapoptotic Bax and Bak in T-cell differentiation and transformation. Biswas S, Shi Q, Matise L, Cleveland S, Dave U, Zinkel S (2010) Blood 116(24): 5237-46
    › Primary publication · 20813900 (PubMed) · PMC3012541 (PubMed Central)
  15. Murine leukemias with retroviral insertions at Lmo2 are predictive of the leukemias induced in SCID-X1 patients following retroviral gene therapy. Davé UP, Akagi K, Tripathi R, Cleveland SM, Thompson MA, Yi M, Stephens R, Downing JR, Jenkins NA, Copeland NG (2009) PLoS Genet 5(5): e1000491
    › Primary publication · 19461887 (PubMed) · PMC2679194 (PubMed Central)
  16. Leukemia takes center (late) stage. Davé UP (2008) Blood 112(6): 2175-6
    › Primary publication · 18779397 (PubMed)
  17. Gene therapy insertional mutagenesis insights. Davé UP, Jenkins NA, Copeland NG (2004) Science 303(5656): 333
    › Primary publication · 14726584 (PubMed)
  18. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Ye J, Rawson RB, Komuro R, Chen X, Davé UP, Prywes R, Brown MS, Goldstein JL (2000) Mol Cell 6(6): 1355-64
    › Primary publication · 11163209 (PubMed)
  19. Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease. Ye J, Davé UP, Grishin NV, Goldstein JL, Brown MS (2000) Proc Natl Acad Sci U S A 97(10): 5123-8
    › Primary publication · 10805775 (PubMed) · PMC25792 (PubMed Central)
  20. Second-site cleavage in sterol regulatory element-binding protein occurs at transmembrane junction as determined by cysteine panning. Duncan EA, Davé UP, Sakai J, Goldstein JL, Brown MS (1998) J Biol Chem 273(28): 17801-9
    › Primary publication · 9651382 (PubMed)