Research groups "CEACAM1 and angiogenesis" and "Glycobiotechnology"
Goal: Understanding and manipulation of inflammatory and angiogenic processes that aid tissue regeneration or that facilitate tumor progression
Research and Expertise: Inflammatory and angiogenic environments
- Translational in vivo models: characterization of inflammatory and angiogenic processes
- characterization of transgenic mouse lines
- identification and characterization of molecular markers, inflammatory cells and the vasculature in inflammatory microenvironments
- characterization and manipulation of inflammatory interfaces
- in vitro angiogenesis assays
- expression, purification and characterization of adhesion molecules
- histological and immunological procedures to identify vascular or inflammatory cell surface molecules
- angiogenesis and inflammation modulated at the adhesion molecule CEACAM1
- Tumor-cell related glycans and inflammation
Current models
- hyperoxic - hypoxic retinopathy
- temporal or chronic occlusion of arteries
- tumors
- implants
Teaching
| Since 2004 |
Clinical Chemistry, Molecular Oncology, Tumor Biology, Molecular Medicine |
| 2011-2012 |
"The sugar code": Lebenswissenschaftliches Kolleg with the German National Academic Foundation, co-instructor with Prof. Dr. T.K. Lindhorst (CAU Kiel) |
| Further Expertise |
project management and personnel development |
Curriculum Vitae
Born in Hamburg, Germany
| 1994 |
B.Sc. Biochemistry/Molecular Biology (Hamburg) |
| 1997 |
M.Sc. Biochemistry/Molecular Biology (Hamburg) |
| 1997-2000 |
Ph.D. thesis, Institute for Clinical Chemistry, UKE and Dept. of Organic Chemistry, University of Hamburg (Profs. C. Wagener and J. Thiem) |
| 2000-2002 |
Postdoctoral training, McGill University, Montréal, Canada
(Prof. N. Beauchemin, Goodman Cancer Center) |
| 2003-current |
Assistant Professor, Institute for Clinical Chemistry, UKE |
| 2008 |
Winner of the Starting grant competition of the German Ministry for Education and Research (BMBF), section "Glycobiotechnology" |
Awards and Fellowships
- Breuer Award of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL)
- Postdoctoral fellowship of the Canadian Cancer Research Society
Memberships
Since 2000: German Society of Clinical Chemistry and Laboratory Medicine (DGKL)
Since 2010: CFG - Consortium for Functional Glycomics
Our research
| Wound healing: resoluation and repair |
vs. |
Tumors: "Wounds that do not heal"* |
 |
|
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Translational models for inflammation and angiogenesis: retinal hypoxia and arterial occlusion (left panel), and mammary tumors and melanomas (right panel). *Dvorak, HF N Engl J Med. 1986 Dec 25;315(26):1650-9
Our translational models include transgenic and knockout mouse lines that are characterized in hypoxic retinopathy, arterial occlusion (figure above, left panel), or chronic cutaneous infection with L. major (Leishmaniasis). In these diseases, the accompanying inflammatory reactions are required to aid healing of insulted tissues and resolution of the pathological status. We are also using these mouse lines in different tumor models. On the contrary, tumor-associated inflammation is a critical process that determines disease malignancy and outcome (figure above, right panel). In mammary carcinomas and melanomas, we characterize tumor-associated inflammation and the inflammatory niches and angiogenic properties of the tumor microenvironment. In the past years, we established in vitro and in vivo models to study angiogenic functions of the cellular adhesion molecule CEACAM1 (CEA-related cell-cell adhesion molecule 1). CEACAM1 is expressed endothelial and inflammatory cells, so it is a molecule present at inflammatory interfaces, since both the endothelium and leukocytes are the major compartments in inflammation. We moved from basic characterization of endothelial CEACAM1 function towards understanding its relevance in inflammatory mircroenvironments: In our key publications, CEACAM1 was identified as a novel angiogenic regulator in vitro and in vivo (Ergün et al. (2000); Horst, Ito et al. (2006), the relevance of its expression on myeloid cells in inflammatory angiogenesis was shown (Horst, Bickert et al. (2009) and comments by Randi and Bussolati (2009) Blood 113:6508-6510)), and CEACAM1-mediated formation of a pro-angiogenic tumor microenvironment was demonstrated (Gerstel et al. (2011) Oncogene). In our group, we provided the first link that CEACAM1 is not only expressed on endothelia and myeloid cells, but that CEACAM1 is actually instrumental in inflammatory niches to promote tissue remodeling.
Publications:
- Gerstel D, Wegwitz F, Jannasch K, Ludewig P, Scheike K, Alves F, Beauchemin, N, Deppert, W, Wagener, C, Horst, AK. CEACAM1 creates a pro-angiogenic tumor microenvironment that supports tumor vessel maturation. Oncogene. 2011 May 2; doi: 10.1038/onc.2011.146; http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2011146a.html
- Schulze J, Bickert T, Beil FT, Zaiss MM, Albers J, Wintges K, Streichert, T., Klätschke, K., Keller, J., Hissnauer, TN, Spiro, AS, Gessner, A, Schett, G, Amling, M, McKenzie, AN, Horst, AK, Schinke, T. Interleukin-33 is expressed in differentiated osteoblasts and blocks osteoclast formation from bone marrow precursor cells. J Bone Miner Res. 2011 Apr;26(4):704-17. http://www.ncbi.nlm.nih.gov/pubmed/20939024
- Schultze A, Decker S, Otten J, Horst AK, Vohwinkel G, Schuch G, Bokemeyer, C, Loges, S, Fiedler, W. TAE226-mediated inhibition of focal adhesion kinase interferes with tumor angiogenesis and vasculogenesis. Invest New Drugs. 2010 Dec;28(6):825-33. http://www.springerlink.com/content/vg27235730786n21/
- Samsen A, Bogoevska V, Klampe B, Bamberger AM, Lucka L, Horst AK, Nollau, P, Wagener, C. DC-SIGN and SRCL bind glycans of carcinoembryonic antigen (CEA) and CEA-related cell adhesion molecule 1 (CEACAM1): recombinant human glycan-binding receptors as analytical tools. Eur J Cell Biol. 2010 Jan;89(1):87-94. http://www.sciencedirect.com/science/article/pii/S0171933509003471
- Hartmann M, Horst AK, Klemm P, Lindhorst TK. A kit for the investigation of live Escherichia coli cell adhesion to glycosylated surfaces. Chem Commun (Camb). 2010 Jan 14;46(2):330-2. http://pubs.rsc.org/en/Content/ArticleLanding/2010/CC/b922525k
- Horst AK*, Bickert T*, Brewig N, Ludewig P, van Rooijen N, Schumacher U, Beauchemin, N, Ito, WD, Fleischer, B, Wagener, C, Ritter, U. CEACAM1+ myeloid cells control angiogenesis in inflammation. Blood. 2009 Jun 25;113(26):6726-36; http://www.ncbi.nlm.nih.gov/pubmed/19273835
** comment by Randi and Bussolati (2009) Blood 113:6508-6510
- Horst AK*, Ito WD*, Dabelstein J, Schumacher U, Sander H, Turbide C, Brümmer, J, Meinertz, T, Beachemin, N, Wagener, C. Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo. J Clin Invest. 2006 Jun;116(6):1596-605. http://www.jci.org/articles/view/24340
- Bogoevska V, Horst A, Klampe B, Lucka L, Wagener C, Nollau P. CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis x residues. Glycobiology. 2006 Mar;16(3):197-209. http://glycob.oxfordjournals.org/content/16/3/197.long
- Ebrahimnejad A, Streichert T, Nollau P, Horst AK, Wagener C, Bamberger AM, Brümmer, J. CEACAM1 enhances invasion and migration of melanocytic and melanoma cells. Am J Pathol. 2004 Nov;165(5):1781-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1618678/?tool=pubmed
- Horst AK, Kötter S, Lindhorst TK, Ludwig A, Brandt E, Wagener C. Binding inhibition of type 1 fimbriae to human granulocytes: a flow cytometric inhibition assay using trivalent cluster mannosides. Med Microbiol Immunol. 2001 Dec;190(3):145-9. http://www.ncbi.nlm.nih.gov/pubmed/11827204
- Ergün S, Kilic N, Ziegeler G, Hansen A, Nollau P, Gotze J, Nollau, P, Wurmbach, JH,
Horst, A, Weil, J, Fernando, M, Wagener, C. CEA-related cell adhesion molecule 1: a potent angiogenic factor and a major effector of vascular endothelial growth factor. Mol Cell. 2000 Feb;5(2):311-20. http://www.sciencedirect.com/science/article/pii/S1097276500804268
* co-first authors
Reviews
Book chapters
- Horst AK, Wagener, C. CEACAM1 Adhesion molecule. In: Schwab M ed. Encyclopedia of Cancer (2nd edition). Heidelberg, Berlin, New York Springer; 2009:562-566.
Funding:
- DFG (German Research Foundation), Individual Grants Programme
- BMBF (German Federal Ministry of Education and Research)
- DFG Priority Programme SPP1190: "The tumor-vessel-interface" (http://www.tumorvessel.de)
Current team members:
Thomas Bickert, Ph.D., M.Sc. Biology
Peter Ludewig, M.D.
Mike Jahn, M.Sc. Biology
Kaja Breckwoldt, cand. M.Sc. Molecular Life Sciences
Sarah Heerdmann, cand. M.Sc. Molecular Life Sciences
Christa Reinhold, technical research assistant
Krimhild Scheike, technical research assistant
Inke Stange, technical research assistant
Julia Kemmling, technical research assistant
No open positions available (current as of July 2011)
Links:
CEACAM1 and CEA-familiy members:
http://www.signaling-gateway.org/molecule/query?afcsid=A003597&type=abstract
http://www.carcinoembryonic-antigen.de/
