David Levy, PhD

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Professor of Pathology and Microbiology
Associate Dean of Collaborative Science
PhD, 1985 Caltech
LAB WEBSITE:
Levy Lab
KEYWORDS:
cancer, JAK-STAT signaling, cell differentiation

Contact Information

NYU School of Medicine
550 1st Ave MSB-548
New York NY 10016 USA
Tel: (212) 263-8192
Fax: (509) 757-3029
E-mail: david.levy@nyumc.org
 


Interaction of signal transduction, transcriptional regulation, and metabolism in the growth and differentiation of stem cells.

 

We are investigating several stem cell-related projects. The first project involves investigation of the molecular mechanisms underlying trophoblast stem (TS) cell proliferation and differentiation and the development of the mammalian placenta. We have found that absence of STAT3 leads to mouse embryonic lethality due to placental failure, the result of inadequate differentiation and survival of critical placental components. In this project, we are elucidating the role of STAT3 during TS cell lineage commitment and differentiation. One aim is to determine how STAT3 maintains TS cell character, in particular, by elucidating its downstream targets. We are also characterizing the specific STAT3 biochemical functions required for placental development.

A second stem cell project explores the commitment of hematopoietic stem cells to myeloid and plasmacytoid dendritic cell differentiation and the role of these cells during innate immunity. We are exploiting methods for conditionally immortalizing lineage committed hematopoietic progenitors that retain the capacity for terminal differentiation. We are using these systems to explore the genes and signaling pathways required for lineage commitment and differentiation and to identify genes required for specific aspects of innate immunity.

A third stem cell project explores the biology of myeloid leukemia-inducing cells following transformation by the Ras oncogene. We have found that Ras transformation requires a mitochondrial function of STAT3 that modulates cellular metabolism. Mice lacking STAT3 or expressing mutant forms of STAT3 in hematopoietic stem cells are protected from cancer development. We are exploring the biochemical basis for STAT3 action during leukemic transformation of hematopoietic stem cells.

Selected Publications: 
  • Chan, Szeman Ruby; Vermi, William; Luo, Jingqin; Lucini, Laura; Rickert, Charles; Fowler, Amy M.; Lonardi, Silvia; Arthur, Cora; Young, Larry J. T.; Levy David E.; Welch, Michael J.; Cardiff, Robert D.; Schreiber, Robert D. STAT1-deficient mice spontaneously develop estrogen receptor alpha-positive luminal mammary carcinomas.  Breast cancer research 2012 ;14(1):R16. PMID: 22264274
  • Gough, Daniel J; Messina, Nicole L; Clarke, Christopher J P; Johnstone, Ricky W; Levy David E. Constitutive Type I Interferon Modulates Homeostatic Balance through Tonic Signaling.  Immunity 2012 Feb;36(2):166-174. PMID: 22365663
  • Lee, J E; Yang, Y -M; Liang, F -X; Gough, D J; Levy D E; Sehgal, P B. Nongenomic STAT5-dependent effects on Golgi apparatus and endoplasmic reticulum structure and function.  American journal of physiology. Cell physiology 2012 March 2012;302(5):804-820. PMID: 22159083
  • Levy David E; Marie, Isabelle J. STATus Report on Tetramers.  Immunity 2012 Apr;36(4):553-555. PMID: 22520849
  • Nancy, Patrice; Tagliani, Elisa; Tay, Chin-Siean; Asp, Patrik; Levy David E; Erlebacher, Adrian. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface.  Science 2012 Jun;336(6086):1317-1321. PMID: 22679098
  • Wang, Y; Levy DE. Comparative evolutionary genomics of the STAT family of transcription factors.  JAK-STAT 2012 2012;1(1):23-33. PMID: 24058748
  • Bogunovic, Dusan; Manches, Olivier; Godefroy, Emmanuelle; Yewdall, Alice; Gallois, Anne; Salazar, Andres M; Marie, Isabelle; Levy David E; Bhardwaj, Nina. TLR4 Engagement during TLR3-Induced Proinflammatory Signaling in Dendritic Cells Promotes IL-10-Mediated Suppression of Antitumor Immunity.  Cancer research 2011 Aug 15;71(16):5467-5476. PMID: 21730023
  • Corcoran, Ryan B; Contino, Gianmarco; Deshpande, Vikram; Tzatsos, Alexandros; Conrad, Claudius; Benes, Cyril H; Levy David E; Settleman, Jeffrey; Engelman, Jeffrey A; Bardeesy, Nabeel. STAT3 Plays a Critical Role in KRAS-Induced Pancreatic Tumorigenesis.  Cancer research 2011 Jul 15;71(14):5020-5029. PMID: 21586612
  • Stritesky GL, Muthukrishnan R, Sehra S, Goswami R, Pham D, Travers J, Nguyen ET, Levy DE, Kaplan MH (2011) The transcription factor STAT3 is required for T helper 2 cell development. Immunity 34: 39-49. PMID: 21215659
  • Manel N, Hogstad B, Wang Y, Levy DE, Unutmaz D, Littman DR (2010) A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 467: 214-217. PMID: 20829794
  • Gough DJ, Messina NL, Hii L, Gould JA, Sabapathy K, Robertson AP, Trapani JA, Levy DE, Hertzog PJ, Clarke CJ, Johnstone RW (2010) Functional crosstalk between type I and II interferon through the regulated expression of STAT1. PLoS Biol. 8: e1000361. PMID: 20436908
  • Demaria M, Giorgi C, Lebiedzinska M, Esposito G, D'Angeli L, Bartoli A, Gough DJ, Turkson J, Levy DE, Watson CJ, Wieckowski MR, Provero P, Pinton P, Poli (2010) A STAT3-mediated metabolic switch is involved in tumor transformation and STAT3 addiction. Aging 2: 823-842. PMID: 21084727
  • Levy DE(2010) NF-kappaB-ISGF3 transcription factor cooperation: coincidence detector or memory chip? Immunity 33: 1-2. PMID: 20643331
  • Gough DJ, Corlett A, Schlessinger K, Wegrezyn J, Larner AC and Levy DE (2009) Mitochondrial Stat3 Supports Ras-Dependent Oncogenic Transformation. Science 324: 1713-1716. PMID: 19556508
  • Gough DJ, Levy DE, Johnstone RW and Clarke CJ (2008) IFNgamma signaling-Does it mean JAK-STAT? Cytokine Growth Factor Rev 19: 383-394. PMID: 18929502