Stephen Hann
Faculty Member
Last active: 5/27/2014

Profile

Our principal research interest focuses on the regulation and function of the oncogene and transcriptional regulator, c-myc. Oncogenic c-Myc is thought to be a driving force in up to 70% of human cancers. Alterations of the c-myc gene are found associated with several types of tumors in several human cancers, including lymphoma and colon, breast and lung cancers. Using a combination of molecular and biochemical techniques, we are investigating the complex role of c-Myc as transcriptional regulator, and its biological roles in cellular proliferation, apoptosis and oncogenesis both in culture and in animals. Our current focus is on proteins that control c-Myc function through direct interaction. We identified two novel binding proteins, the tumor suppressor ARF and nucleophosmin, which have opposite effects on c-Myc. ARF appears to negatively affect c-Myc transformation by controlling c-Myc-induced apoptosis through a new mechanism. In contrast, nucleophosmin is necessary for the ability of c-Myc to transform cells efficiently. Understanding the mechanism and functional consequences of these interactions will allow us to develop effective therapeutic approaches to inhibit c-Myc-induced tumorigenesis. We are also continuing to investigate the mechanism of c-Myc transcriptional activity, including the identification of target genes that mediate c-Myc function and the role of c-Myc post-translational modifications, proteolysis and localization.

Publications

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

Featured publications are shown below:

  1. Thr 163 phosphorylation causes Mcl-1 stabilization when degradation is independent of the adjacent GSK3-targeted phosphodegron, promoting drug resistance in cancer. Nifoussi SK, Vrana JA, Domina AM, De Biasio A, Gui J, Gregory MA, Hann SR, Craig RW (2012) PLoS One 7(10): e47060
    › Primary publication · 23056582 (PubMed) · PMC3467206 (PubMed Central)
  2. c-Myc represses FOXO3a-mediated transcription of the gene encoding the p27(Kip1) cyclin dependent kinase inhibitor. Chandramohan V, Mineva ND, Burke B, Jeay S, Wu M, Shen J, Yang W, Hann SR, Sonenshein GE (2008) J Cell Biochem 104(6): 2091-106
    › Primary publication · 18393360 (PubMed)
  3. Recapitulation of germ cell- and pituitary-specific expression with 1.6 kb of the cystatin-related epididymal spermatogenic (Cres) gene promoter in transgenic mice. Hsia N, Brousal JP, Hann SR, Cornwall GA (2005) J Androl 26(2): 249-57
    › Primary publication · 15713831 (PubMed)
  4. MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol. Domina AM, Vrana JA, Gregory MA, Hann SR, Craig RW (2004) Oncogene 23(31): 5301-15
    › Primary publication · 15241487 (PubMed)
  5. Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. Greenberg RA, O'Hagan RC, Deng H, Xiao Q, Hann SR, Adams RR, Lichtsteiner S, Chin L, Morin GB, DePinho RA (1999) Oncogene 18(5): 1219-26
    › Primary publication · 10022128 (PubMed)
  6. Specialized gene expression in the epididymis. Cornwall GA, Hann SR (1995) J Androl 16(5): 379-83
    › Primary publication · 8575976 (PubMed)
  7. Variant Max protein, derived by alternative splicing, associates with c-Myc in vivo and inhibits transactivation. Arsura M, Deshpande A, Hann SR, Sonenshein GE (1995) Mol Cell Biol 15(12): 6702-9
    › Primary publication · 8524235 (PubMed) · PMC230923 (PubMed Central)
  8. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Davis AC, Wims M, Spotts GD, Hann SR, Bradley A (1993) Genes Dev 7(4): 671-82
    › Primary publication · 8458579 (PubMed)
  9. A link between increased transforming activity of lymphoma-derived MYC mutant alleles, their defective regulation by p107, and altered phosphorylation of the c-Myc transactivation domain. Hoang AT, Lutterbach B, Lewis BC, Yano T, Chou TY, Barrett JF, Raffeld M, Hann SR, Dang CV (1995) Mol Cell Biol 15(8): 4031-42
    › Primary publication · 7623799 (PubMed) · PMC230642 (PubMed Central)
  10. Transient appearance of CRES protein during spermatogenesis and caput epididymal sperm maturation. Cornwall GA, Hann SR (1995) Mol Reprod Dev 41(1): 37-46
    › Primary publication · 7619504 (PubMed)
  11. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Hann SR, King MW, Bentley DL, Anderson CW, Eisenman RN (1988) Cell 52(2): 185-95
    › Primary publication · 3277717 (PubMed)
  12. Posttranscriptional changes in growth factor-inducible gene regulation caused by antiproliferative interferons. Levine RA, Seshadri T, Hann SR, Campisi J (1990) Cell Regul 1(2): 215-26
    › Primary publication · 2100198 (PubMed) · PMC361447 (PubMed Central)