Tilman Heise, Ph.D.
                              Assistant Professor
     
     
  2007 Assistant Professor, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC
     
  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, California, USA
     
  1995 Ph.D, Georg-August-University of Goettingen, Germany
     
  1992 Diploma, Georg-August-University of Goettingen, Germany
     


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

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 regulating gene expression. Malfunction in those processes correlating with many human diseases.

Our long-term goal is to identify RNA binding proteins, which are misregulated in cancerous cells. To firmly establish their causal role in cancer development we reveal their cellular functions and demonstrate that misregulation of those functions are of advantage for cancerous cells. Our research focuses on the cancer-associated RNA-binding protein La, a known RNA chaperone, which regulates e.g. the translation of cellular key factors. 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 also in in vitro assays.

 

Selected Publications
 
  • Sommer G., Heise T. Posttranscriptional control of HBV gene expression. Frontiers in Bioscience 5533-5547, May 1, 2008, review
  • Cordes S, Kusov Y, Heise T, Gauss-Müller V. La autoantigen suppresses IRES-dependent translation of the hepatitis A virus. Biochem Biophys Res Commun. 2008 Feb 15; [Epub ahead of print]
  • Schwalbe M, Ohlenschläger O, Marchanka A, Ramachandran R, Häfner S, Heise T, Görlach M. Solution structure of stem-loop {alpha} of the hepatitis B virus post-transcriptional regulatory element. Nucleic Acids Res. 2008 Feb 7; [Epub ahead of print ]
  • van Niekerk EA, Willis DE, Chang JH, Reumann K, Heise T, Twiss JL. Sumoylation in axons triggers retrograde transport of the RNA-binding protein La . Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12913-8 . Research Highlights published in Nature Reviews Neuroscience, 2007, Vol 8.
  • Kraunus J. Zychlinski D, Heise T, Galla J, Bohne J, Baum C. Mur ine leukemia virus regulates alternative splicing through sequences upstream of the 5' splice site. J Biol Chem. 2006 Dec 8;281(49):37381-90.
  • Märschenz S, Endres AS, Brinckmann A, Heise T, Kristiansen G, Nürnberg P, Krüger DH, Günther S, 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 Sep;131(3):957-60.
  • Heise T , Sommer G, Reumann K, Will H, Schaal H. The hepatitis B virus PRE contains a splicing regulatory element. Nucleic Acid Research, 2006, Vol. 34(1):353-363
  • Horke S, Reumann K, Schulze C, Große F, Heise T. The La-motif and the RRMs of hLa contribute individually to RNA recognition and subcellular localization. J Biol Chem. 2004 Nov 26; 279(48):50302-50309.
  • Ehlers I, Horke S, Reumann K, Rang A, Grosse F, Will H, Heise T . Functional Characterization of the Interaction between Human La and Hepatitis B Virus RNA in vivo and in vitro. J Biol Chem. 2004 Oct 15;279(42):43437-47.
  • Horke S, Reumann K, Schweizer M, Will H, 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 Jun 18;279(25):26563-70.
  • Horke S, Reumann K, Rang A, 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, 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

Book chapters

Heise T , Dandri M, Petersen J, Rang A, Burda M, Will H. Modulation of HBV-infection by viral and cellular mechanisms. Workshop 2000; Chronic Hepatitis: New Concepts of Pathogenesis, Diagnosis and treatment-Falk; Kluwer academic press, UK