Biomedical Research Education & Training
Faculty Member

Hann, Stephen R., Ph.D.
Professor of Cell and Developmental Biology

Lab Url: N/A

Phone Number: 615-343-4344

Email Address: steve.hann@vanderbilt.edu

Hann, Stephen's picture
Academic history
A.B., University of California, Berkeley
Ph.D., University of California, Riverside

Office Address   Mailing Address

B-2317A/B-2324 MCN

B-2317 Medical Center North 8240


Research Keywords
Apoptosis, Cancer, Cell cycle, Chromatin, Gene regulation, Immortalization, Mouse, Phosphorylation, Post-translational modification, Protein structure, Proteomics, Signal Transduction, Transcription, Transcription Factor, Tumor Suppressors, Transformation, Translation

Research Description
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
Li, Z, Hann, SR. Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated rDNA transcription. Oncogene, 2012

Boone, DN, Hann, SR. The Myc-ARF-Egr1 pathway: unleashing the apoptotic power of c-Myc. Cell Cycle, 10(13), 2043-4, 2011 PMCID:3234342

Boone, DN, Qi, Y, Li, Z, Hann, SR. Egr1 mediates p53-independent c-Myc-induced apoptosis via a noncanonical ARF-dependent transcriptional mechanism. Proc Natl Acad Sci U S A, 108(2), 632-7, 2011 PMCID:3021028

Li, Z, Hann, SR. The Myc-nucleophosmin-ARF network: a complex web unveiled. Cell Cycle, 8(17), 2703-7, 2009

Li, Z, Boone, D, Hann, SR. Nucleophosmin interacts directly with c-Myc and controls c-Myc-induced hyperproliferation and transformation. Proc Natl Acad Sci U S A, 105(48), 18794-9, 2008 PMCID:2596228

Hann, SR. Role of post-translational modifications in regulating c-Myc proteolysis, transcriptional activity and biological function. Semin Cancer Biol, 16(4), 288-302, 2006

Vaknin, UA, Hann, SR. The alpha1 subunit of GABA(A) receptor is repressed by c-Myc and is pro-apoptotic. J Cell Biochem, 97 (5), 1094-103, 2006

Gregory, MA, Qi, Y, Hann, SR. The ARF tumor suppressor: keeping Myc on a leash. Cell Cycle, 4(2), 249-52, 2005

Hsia, N., Brousal, J., Hann, S.R., and Cornwall, G.A. . Germ-cell specific expression of a cystatin-related epididymal spermatogenic (CRES) promoter-CAT transgene. J. of Andrology , 26, 249-257, 2005

Domina, A.M., Vrana, J.A., Gregory, M.A., Hann, S.R., and Craig, R.C. . MCL 1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with okadaic acid or taxol. Oncogene , 8, 5301-5315, 2004

Qi, Ying, Gregory, Mark A, Li, Zhaoliang, Brousal, Jeffrey P, West, Kimberly, Hann, Stephen R. p19ARF directly and differentially controls the functions of c-Myc independently of p53. Nature, 431(7009), 712-7, 2004

Gregory, Mark A, Qi, Ying, Hann, Stephen R. Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J Biol Chem, 278(51), 51606-12, 2003

Cornwall, G A, Collis, R, Xiao, Q, Hsia, N, Hann, S R, . B-Myc, a proximal caput epididymal protein, is dependent on androgens and testicular factors for expression.. Biol Reprod, 64, 1600-7, 2001

Chang, D W, Claassen, G F, Hann, S R, Cole, M D, . The c-Myc transactivation domain is a direct modulator of apoptotic versus proliferative signals.. Mol Cell Biol, 20, 4309-19, 2000 PMCID:85798

Claassen, G F, Hann, S R, . A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta -induced cell-cycle arrest.. Proc Natl Acad Sci U S A, 97, 9498-503, 2000 PMCID:16893

Gregory, M A, Hann, S R. c-Myc proteolysis by the ubiquitin-proteasome pathway: stabilization of c-Myc in Burkitt's lymphoma cells. Mol Cell Biol, 20(7), 2423-35, 2000 PMCID:85426

Gregory, M A, Xiao, Q, Cornwall, G A, Lutterbach, B, Hann, S R, . B-Myc is preferentially expressed in hormonally-controlled tissues and inhibits cellular proliferation.. Oncogene, 19, 4886-95, 2000

Niklinski, J, Claassen, G, Meyers, C, Gregory, M A, Allegra, C J, Kaye, F J, Hann, S R, Zajac-Kaye, M, . Disruption of Myc-tubulin interaction by hyperphosphorylation of c-Myc during mitosis or by constitutive hyperphosphorylation of mutant c-Myc in Burkitt's lymphoma.. Mol Cell Biol, 20, 5276-84, 2000 PMCID:85977

Claassen, G F, Hann, S R. Myc-mediated transformation: the repression connection. Oncogene, 18(19), 2925-33, 1999

Greenberg, R., O'Hagan, R., Deng H., Xiao, Q., Hann, S., Adams, R., Lichtsteiner, S., Chin, L., Morin, G. and DePinho, R. Telomerase Reverse Transcriptase Gene is a Direct Target of c-Myc but is not functionally equivalent in cellular transformation. Oncogene, 18, 1219-1226, 1999

Lutterbach, B, Hann, S R. c-Myc transactivation domain-associated kinases: questionable role for map kinases in c-Myc phosphorylation. J Cell Biochem, 72(4), 483-91, 1999

Xiao, Q, Claassen, G, Shi, J, Adachi, S, Sedivy, J, Hann, S R. Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis. Genes Dev, 12(24), 3803-8, 1998 PMCID:317265

Lutterbach, B, Hann, S R. Overexpression of c-Myc and cell immortalization alters c-Myc phosphorylation. Oncogene, 14(8), 967-75, 1997

Spotts, G D, Patel, S V, Xiao, Q, Hann, S R. Identification of downstream-initiated c-Myc proteins which are dominant-negative inhibitors of transactivation by full-length c-Myc proteins. Mol Cell Biol, 17(3), 1459-68, 1997 PMCID:231871

Arsura, M., Deshpande, A., Hann, S., and Sonenshein, G. Varient Max protein, derived by alternative splicing, associates with c-myc in vivo and inhibits transactivation. Mol. Cell. Biol., 15, 6702-6709, 1995

Cornwall, G.A. and Hann, S. R. Transient appearance of the CRES protein during spermatogenesis and caput epididymal sperm maturation. Mol. Reprod. and Develop., 41, 37-46, 1995

Cornwall, G.A. and Hann, S.R. Specialized gene expression in the epididymis. Journal of Andrology, 16, 379-383, 1995

Hann, S R. Methionine deprivation regulates the translation of functionally-distinct c-Myc proteins. Adv Exp Med Biol, 375, 107-16, 1995

Hoang, A., Lutterbach, B., Lewis, B., Yano, T., Chou, Y., Barrett, J. Raffeld, M., Hann, S. and Dang, C. Increased transfon-ning activity of lymphoma-derived MYC mutant alleles results from defective regulation by plO7 and altered phosphorylation of the MYC transactivation domain. Mol. Cell. Biol., 15, 4031-4042, 1995

Hann, S R. Regulation and function of non-AUG-initiated proto-oncogenes. Biochimie, 76(9), 880-6, 1994

Hann, S R, Dixit, M, Sears, R C, Sealy, L. The alternatively initiated c-Myc proteins differentially regulate transcription through a noncanonical DNA-binding site. Genes Dev, 8(20), 2441-52, 1994

Hann, S.R. Regulation and function of non-AUG-initiated proto-oncogenes. Biochiinie, 76, 880-886, 1994

Lutterbach, B, Hann, S R. Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis. Mol Cell Biol, 14(8), 5510-22, 1994 PMCID:359071

Davis, A.C., Wims, M., Spotts, G.D., Hann, S.R. and Bradley, A. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygote embryos and reduced fertility in heterozygous female mice. Genes and Development, 7, 671-682, 1993

Cornwall, G A, Orgebin-Crist, M C, Hann, S R. Differential expression of the mouse mitochondrial genes and the mitochondrial RNA-processing endoribonuclease RNA by androgens. Mol Endocrinol, 6(7), 1032-42, 1992

Cornwall, G A, Orgebin-Crist, M C, Hann, S R. The CRES gene: a unique testis-regulated gene related to the cystatin family is highly restricted in its expression to the proximal region of the mouse epididymis. Mol Endocrinol, 6(10), 1653-64, 1992

Cornwall, G A, Orgebin-Crist, M C, Hann, S R. Expression of an endogenous murine leukemia virus-related proviral sequence is androgen regulated and primarily restricted to the epididymis/vas deferens and oviduct/uterus. Biol Reprod, 47(4), 665-75, 1992

Hann, S R, Sloan-Brown, K, Spotts, G D. Translational activation of the non-AUG-initiated c-myc 1 protein at high cell densities due to methionine deprivation. Genes Dev, 6(7), 1229-40, 1992

Robinson-Benion, C, Salhany, K E, Hann, S R, Holt, J T. Antisense inhibition of c-myc expression reveals common and distinct mechanisms of growth inhibition by TGF beta and TNF alpha. J Cell Biochem, 45(2), 188-95, 1991

Levine, R.A., Seshadri, T., Hann, S.R. and Campisi, J. Posttranscriptioal changes in growth factor- inducible gene regulation caused by antiproliferative interferons. Gene Regulation, 1, 215-226, 1990

Spotts, G D, Hann, S R. Enhanced translation and increased turnover of c-myc proteins occur during differentiation of murine erythroleukemia cells. Mol Cell Biol, 10(8), 3952-64, 1990 PMCID:360906

Hann, S.R., King, M.W., Bentley, D.L., Anderson, C.W. and Eisemnan, R.N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Cell, 52, 185-195, 1988

Eisenman, R.N., Tachibana, C.Y., Abrams, H.D., Hann, S.R.. v-myc and c-myc-encoded proteins are associated with the nuclear matrix. . Mol. Cell. Biol., 5, 114-126, 1985

Hann, S.R., Thompson, C.B., Eiserunan, R.N. c-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells. Nature, 314, 366-369, 1985

Hann, S.R., Eisemnan, R.N. Proteins encoded by the human c-myc oncogene: Differential expression in neoplastic cells. Mol Cell Biol, 4, 2486-2497, 1984

Hann, S. R., Abrams, H. D., Rohrschneider, L. R., Eisenman, R. N. Proteins encoded by the v-myc and c-myc oncogenes: Identification and localization in acute leukemia virus transformants and bursal lymphoma cell lines. Cell, 34, 789-798, 1983


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
07/12/2012