Research Activities of the
Mononuclear Phagocyte Biology - Gene Regulation Laboratory

Group web site (German): http://www.ag-rehli.de  

Group members:
(for e-Mail please type firstname.lastname@klinik.uni-regensburg.de)
Dr. rer. nat Michael Aigner (Dipl. Biol.)
Dr. rer. nat Carol El Chartouni (Dipl. Biol.)
Claudia Gebhard (Dipl. Biol.)
Maja Klug (Dipl. Biol.)
Monika Lichtinger (Dipl. Biol.)
Sabine Pape TA
Thu Hang Pham, PhD
Elmar Schilling (Dipl. Biol.)
Lucia Schwarzfischer TA
Tobias Weil (Dipl. Biol.)

Medical students:
Jochen Spiess
Stephan Kandsperger

Research - Areas of Interest   Area of Interest I: Mononuclear Phagocyte Biology

Mononuclear phagocytes, though heterogenous in morphology, biochemistry and function, all originate from blood monocytes which migrate into the various tissues where they mature into the various types of tissue macrophages or two other specialized cell types: the antigen-presenting dendritic cells or the multinucleated bone-resorbing osteoclast. Mononuclear phagocytes fulfil important roles in development, tissue homeostasis, inflammation and wound healing and are a major cell population in most of the tissues in the body. A number of research projects in our lab focus' on the analysis of functional and developmental processes in mononuclear phagocytes, in particular mechanisms of specific gene regulation in mononuclear phagocytes. In one project, we are studying the transcriptional regulation of interesting marker genes (Carboxypeptidase M, HC-gp 39 and Chitotriosidase) which are not expressed in MO but strongly upregulated during late MAC differentiation. Other projects focus on the function of specific transcription factors in mononuclear phagocyte differentiation, in particular those regulating alternative vs. classical activation pathways. Our lab is also interested in the regulation of Toll-like receptors in mononuclear phagocytes of mouse and man. We are analysing transcriptional mechanisms regulating the expression of TLRs and we are interested in the effect of species-specific regulatory differences between mice and humans.

Area of Interest II: Epigentics and Gene Regulation

In mammals, methylation of cytosine residues in CpG dinucleotides is a frequent epigenetic mark that is required for normal embryonic development. DNA methylation plays important roles in gene regulation, e.g. in X chromosome inactivation, imprinting, or silencing of retrotransposons and is mostly associated with gene repression. Aberrant methylation patterns have been associated with dieseases such as cancer, where the epigenetic silencing of tumor-suppressor genes often coincides with the aberrant methylation of CpG dinucleotides in so called CpG islands. Hypermethylation of CpG islands appears to be a tumor-type specific event and current research efforts concentrate on finding ways to exploit the diagnostic and therapeutic implications of the abnormalities. We developed tools that enable the generation of genome-wide profiles of DNA methylation in normal or cancer cells, and several lab members investigate the impact of CpG methylation on gene regulation and cancer development.

Selected References (2000 to date):

Rehli, M., Poltorak,A., Schwarzfischer, L., Krause, S.W., Andreesen, R., Beutler, B. (2000). PU.1 and interferon consensus sequence binding protein (ICSBP) regulate the myeloid expression of the human Toll-like receptor 4 gene.
J. Biol. Chem. 275, 9773-9781 [full text]

Krause, S.W., Rehli, M., Heinz, S., Ebner, R., Andreesen, R. (2000). Chararacterization of MAX.3 Antigen, a Glycoprotein expressed on Mature Macrophages, Dendritic Cells and Blood Platelets: Identity with CD84.
Biochem. J. 346, 729-736. [full text]

Beutler, B. and M. Rehli. (2002). Evolution of the TIR, tolls and TLRs: functional inferences from computational biology.
Curr. Top. Microbiol. Immunol. 270:1-21.:1-21.

Rehli, M. (2002). Of mice and men: species variations of Toll-like receptor expression.
Trends Immunol. 23:375-378.

Haehnel, V., L. Schwarzfischer, M. J. Fenton, and M. Rehli. (2002). Transcriptional regulation of the human toll-like receptor 2 gene in monocytes and macrophages.
J. Immunol. 168:5629-5637. [full text]

Heinz,S., Haehnel,V., Karaghiosoff,M., Schwarzfischer,L., Muller,M., Krause,S.W., and Rehli,M. (2003). Species-specific regulation of Toll-like receptor 3 genes in men and mice.
J. Biol. Chem. 278, 21502-21509. [full text]

Rehli,M., Niller,H.H., Ammon,C., Langmann,S., Schwarzfischer,L., Andreesen,R., and Krause,S.W. (2003). Transcriptional regulation of CHI3L1, a marker gene for late stages of macrophage differentiation.
J. Biol. Chem. 278, 44058-44067. [full text]

Rehli,M., Sulzbacher,S., Pape,S., Ravasi,T., Wells,C.A., Heinz,S., Sollner,L., El Chartouni,C., Krause,S.W., Steingrimsson,E., Hume,D.A., and Andreesen,R. (2005). Transcription Factor Tfec Contributes to the IL-4-Inducible Expression of a Small Group of Genes in Mouse Macrophages Including the Granulocyte Colony-Stimulating Factor Receptor.
J. Immunol. 174, 7111-7122. [full text]

Gebhard,C., Schwarzfischer,L., Pham,T.H., Schilling,E., Klug,M., Andreesen,R., and Rehli,M. (2006). Genome-wide profiling of CpG methylation identifies novel targets of aberrant hypermethylation in myeloid leukemia.
Cancer Res. 66, 6118-6128. [abstract]

Gebhard,C., Schwarzfischer,L., Pham,T.H., Andreesen,R., Mackensen,A., and Rehli,M. (2006). Rapid and sensitive detection of CpG-methylation using methyl-binding (MB)-PCR.
Nucleic Acids Res. 34, e82. [full text]