Skip Navigation
 

Department of biochemistry and Molecular biology

Tilman Heise, PhD

Assistant ProfessorTilman Heise, PhD
Biochemistry and Molecular Biology

1999-2007     Group leader, Dept of General Virology, Heinrich-Pette Institut fuer
                          Experimentelle Virologie und Immunologie, Hamburg, Germany
1996-1998     Post-doctoral Fellow, Dept Experimental Medicine,
                         Scripps Research Institute


Education
1995     Ph.D, Georg-August-University of Goettingen, Germany
1992     Diploma, Georg-August-University of Goettingen, Germany


Contact Info
Email:
heise@musc.edu
Office: 843-792-6979
Lab: 843-792-7848
Fax: 843-792-8568

BSB-507 (lab)
BSB 518E (office)

Research Interests

The maturation of mRNAs is a complex row of processing steps crucial for gene expression. The co-transcriptional processing, the nuclear export, the translation and the decay of a specific mRNA are strictly regulated events. Malfunction in those processes correlating with the development of human diseases.
Our long-term goal is to firmly establish the role and function of RNA-binding proteins in cancer development and viral infection. Our research focuses on the cancer-associated RNA-binding protein La, a known RNA chaperone, which regulates e.g. the translation of cellular and viral key factors. Currently we focus on the regulation of La functions by posttranslational modification such as SUMOylation and phosphorylation. Furthermore, we aim to develop high-throughput assay to identify small molecule inhibitors blocking the binding of La to specific RNA molecules. In addition we are studying the function of other RNA-binding proteins as well as the cellular function of a fusion protein, consisting of an RNA-binding protein and a transcription factor, implicated in the development of child hood leukemia.

Methods: We are applying a broad range of techniques used in molecular biology, biochemistry and cell biology including quantitative PCR, Chromatin immunoprecipitation assays (ChIP), co-immunoprecipitation, in vitro transcription, in vitro translation, polyribosomal gradients and RNA interference. We are developing reporter assays for functional studies in living cells. Gel retardation assay are applied to study the interaction between RNA-binding proteins and RNA molecules and immunofluorescence microscopy is used to study cellular localization, trafficking and co-localization of proteins in fixed and living cells. We demonstrate the close association of specific RNA molecules and a specific RNA-binding protein by RNA Fluorescence In Situ Hybridization (RNA FISH). In addition we are also studying posttranslational modifications of proteins like SUMOylation and phosphorylation. Furthermore, we are purifying recombinant proteins and protein complexes from cells to study their function.

Recent Publications

Tang J, Zhang Z-H, Huang M, Heise T, Zhang J, and Liu G-L. Phosphorylation of human La protein at Ser366 by casein kinase II contributes to hepatitis B virus replication and expression in vitro. Journal Viral Hepatitis. Article first published online: 9 Jul 2012
DOI: 10.1111/j.1365-2893.2012.01636.x

Sommer G, Rossa C, Chi AC, Neville BW, and Heise T. Implication of RNA binding protein La in proliferation, migration and invasion of lymph node metastasized hypopharyngeal SCC cell. PLoS One. 2011 6(10):e25402. Epub 2011 Oct 10, PMCID: PMC3189910

Sommer G, Dittmann J, Kuehnert J, Reumann K, Schwartz PE, Will H, Coulter BL, Smith MT, and Heise T. The RNA-binding protein La contributes to cell proliferation and CCND1 expression. Oncogene. 2010 Sep 20. [Epub ahead of print] PMID: 20856207

Sommer G and Heise T. Posttranscriptional control of HBV gene expression. Frontiers in Bioscience 2008 13:5533-5547, invited review.

Cordes S, Kusov Y, Heise T, and Gauss-Müller V. La autoantigen suppresses IRES dependent translation of the hepatitis A virus. Biochem Biophys Res Commun. 2008 368(4):1014-9.

Schwalbe M, Ohlenschläger O, Marchanka A, Ramachandran R, Häfner S, Heise T, and Görlach M. Solution structure of stem-loop {alpha} of the hepatitis B virus post-transcriptional regulatory element. Nucleic Acids Res. 2008 36(5):1681-9.

van Niekerk EA, Willis DE, Chang JH, Reumann K, Heise T, and Twiss JL. Sumoylation in axons triggers retrograde transport of the RNA-binding protein La. Proc Natl Acad Sci U S A. 2007 J104(31):12913-8. Epub 2007 Jul 23. Research highlights published in Nature Reviews Neuroscience, 2007, vol. 8.

Kraunus J, Zychlinski D, Heise T, Galla M, Bohne J, and Baum C. Murine leukemia virus regulates alternative splicing through sequences upstream of the 5' splice site. J Biol Chem. 2006 281(49):37381-90. Epub 2006 Oct 11.

Marschenz S, Endres AS, Brinckmann A, Heise T, Kristiansen G, Nurnberg P, Kruger DH, Gunther S, and Meisel H. Functional analysis of complex hepatitis B virus variants associated with development of liver cirrhosis. Gastroenterology. 2006 Sep;131(3):765-80. Comment in: Gastroenterology. 2006 131(3):957-60.

Heise T*, Sommer G, Reumann K, Will H, and Schaal H. The hepatitis B virus PRE contains a splicing regulatory element. Nucleic Acid Research 2006 34(1):353-363. * corresponding author

Horke S, Reumann K, Schulze C, Große F, and Heise T. The La-motif and the RRMs of hLa contribute individually to RNA recognition and subcellular localization. J Biol Chem. 2004 279(48):50302-50309. Epub 2004 Sep 15.

Ehlers I, Horke S, Reumann K, Rang A, Grosse F, Will H, and Heise T. Functional Characterization of the Interaction between Human La and Hepatitis B Virus RNA. J Biol Chem. 2004 279(42):43437-47. Epub 2004 Aug 09

Horke S, Reumann K, Schweizer M, Will H, and Heise T. Nuclear trafficking of La protein depends on a newly identified nucleolar localization signal and the ability to bind RNA. J Biol Chem. 2004 279(25):26563-70. Epub 2004 Apr 01.

Horke S, Reumann K, Rang A, and Heise T. Molecular characterization of the human La protein-Hepatitis B virus RNA.B interaction in vitro. J Biol Chem. 2002 277(38):34949-58.

Rang A, Bruns M, Heise T, Will H. Antiviral activity of interferon-alpha against Hepatitis B virus can be studied in non-hepatic cells and is independent of MxA. J Biol Chem 2002 277(10):7645-7.

Heise T, Guidotti LG, and Chisari FV. Characterization of nuclear RNases that cleave Hepatitis B virus RNA near the La protein binding site.  J Virol 2001 75(15):6874-6883.

Rang A, Heise T, Will H. Lack of a role of the interferon-stimulated response element-like region in interferon alpha -induced suppression of Hepatitis B virus in vitro. J Biol Chem 2001 276(5):3531-5.

Heise T, Guidotti LG, Chisari FV. La autoantigen specifically recognizes a predicted stem-loop in hepatitis B virus RNA.
J Virol 1999 73(7):5767-76.

Heise T, Guidotti LG, Cavanaugh VJ, Chisari FV. Hepatitis B virus RNA-binding proteins associated with cytokine-induced clearance of viral RNA from the liver of transgenic mice.  J Virol 1999 73(1):474-81.

Heise, T, Krones A, Nath A, Jungermann K, Christ B. Parallel acceleration of Phosphoenolpyruvate Carboxykinase mRNA degradation and increase in ribonuclease activity induced by Insulin in culturd rat hepatocytes. Biol. Chem. Hoppe-Seyler 1998 379:875-883.

Heise T, Nath A, Jungermann K, Christ B. Purification of a RNA-binding protein from rat liver. J Biol Chem 1997 272:20222-20229.

Modaressi S, Christ B, Bratke J, Zahn S, Heise T, Jungermann K. Molecular cloning, sequencing and expression of the cDNA of mitochondrial phosphoenolpyruvate carboxykinase from human liver. Biochem J 1996 315:807-814.

Christ B, Heise T, Jungermann K. Binding of cytosolic protein from cultured rat hepatocytes to the 3'-end of phosphoenolpyruvate carboxykinase mRNA - Significance for protein-mediated mRNA stabilization. Biochem Biophys Res Commun 1991 177:1273-1282.

top of page

 
 
 

© 2012  Medical University of South Carolina | Disclaimer