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AG Nierhoff
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AG Nierhoff

Address

Dept. of Gastroenterology and Hepatology
University Hospital of Cologne, Cologne, Germany Building 37, Room 1-005
Telephone: +49 221 478-7280
E-Mail: [Email protection active, please enable JavaScript.]

Team

  • Priv.-Doz. Dr. Dirk Nierhoff, MD
  • Dr. Susanne Zweerinck, Postdoktorandin
  • Dr. Vera Mück
  • Andrea Bowe
  • Elisabeth Konze, Technician
  • Gudrun Suckau, Technician
  • Gitta Jakob, Technician
  • Gisela Holz, Technician


Projects actively being pursued

  1. Liver stem/progenitor cells
    The existence of hepatic stem cells in the adult liver was suggested almost 60 years ago, yet the isolation of these cells has not been achieved. However, hepatoblasts from the fetal liver exhibit many properties expected for hepatic stem/progenitor cells and numerous studies have reported the successful isolation of hepatoblasts.
    Our research group focuses on the identification, characterization and isolation of liver stem/progenitor cells. More recent studies have shown that Liv2, delta-like 1 homolog (Dlk1) (Drosophila) and E-cadherin are specific cell surface markers of hepatoblasts within the developing liver. In previous studies, we showed that these surface markers specifically detect α-fetoprotein (Afp)+ cells in the murine fetal liver at embryonic day (ED) 12.5 and we also identified Sca-1 (a general stem cell marker) as another surface marker expressed on murine hepatoblasts (Nierhoff er al. 2005). To identify additional surface markers expressed by murine hepatoblasts, we performed a cDNA microarray analysis comparing purified hepatoblasts isolated from ED13.5 mouse fetal liver with adult liver (Nierhoff et al. 2007).
    These markers will be utilized to detect and isolate stem/progenitor cell populations within the adult or regenerating liver (financially supported by the Koeln Fortune Program). In the future, these cell populations will be used for cell transplantation studies to show their in vivo liver repopulation capacity.

  2. Neighbor of Punc E11 (Nope)
    In our microarray analysis, the surface protein Nope (Neighbor of Punc E11) showed a significantly higher expression level in hepatoblasts than in adult liver. Nope is a protein thought to be essential for axon guidance by similarity with its family members neogenin and deleted in colorectal cancer (Dcc). Neogenin is thought to act in netrin receptor-adhesive clustering and it may be involved in maintenance of multipotent progenitor cells. It is also reported to be expressed during transition of undifferentiated into differentiated cell types. In the liver, the function of Nope may be in homotypic cell-cell contact, perhaps guiding the formation of hepatic cords. Currently, we are working on the expression of Nope during murine liver development and its potential functional relevance.

  3. New biomarkers for hepatocellular carcinoma (HCC)
    HCC is the 5th common malignancy worldwide and the incidence has almost doubled within the last 40 years. As established markers fail to detect up to one third of HCC, the identification of new markers is particularly relevant. We have recently identified new cell surface markers of murine fetal liver stem cells by cDNA microarray (Nierhoff et al. 2007). In analogy to established HCC markers like α-Fetoprotein (Afp) and Glypican-3 (Gpc-3), we currently investigate the relevance of these markers as potential onco-fetal markers of HCC and their expression during hepatocarcinogenesis.

References

Major Research Articles

1) Gabriel E, Schievenbusch S, Kolossov E, Hengstler JG, Rotshteyn T, Bohlen H, Nierhoff D, Hescheler J, Drobinskaya I.

Differentiation and selection of hepatocyte precursors in suspension spheroid culture of transgenic murine embryonic stem cells.

PLoS One, 2012; 7(9):e44912. Epub 2012 Sep 24.

2) Schievenbusch S, Sauer E, Curth H-M, Schulte S, Demir M, Toex U, Goeser T and Nierhoff D.

Neighbor of Punc E11 (Nope): Expression pattern of the new hepatic stem/progenitor cell marker during murine liver development.

Stem Cells and Development, 2012, Sep 20; 21(14):2656-66.

3) Marquardt JU, Quasdorff M, Varnholt H, Curth HM, Mesghenna S, Protzer U, Goeser T, Nierhoff D.

Neighbor of Punc E11, a novel onco-fetal marker for hepatocellular carcinoma.

Int J Cancer, 2011, May 15; 128(10):2353-63.

4)  Nierhoff D, LeVoci L, Schulte S, Goeser T, Rogler LE and Shafritz DA. 

New cell surface markers for murine fetal hepatic stem cells identified through high density complementary DNA microarrays. 

Hepatology, 2007, Aug; 46(2):535-47.

5) Gouon-Evans V, Boussemart L, Gadue P, Nierhoff D, Koehler CI, Kubo A, Shafritz DA, and Keller G. 

BMP-4 is required for hepatic specification of mouse embryonic stem cell-derived definitive endoderm. 

Nature Biotechnology, 2006, Nov; 24(11):1402-11.

6) Shafritz DA, Oertel M, Menthena A, Nierhoff D and Dabeva MA. 

Liver stem cells and prospects for liver reconstitution by transplanted cells.

Hepatology, 2006, Feb; 43(2 Suppl 1):S89 – 98.

7) Ju W, Ogawa A, Heyer J, Nierhoff D, Liping Y, Kucherlapati R, Shafritz DA, and Boettinger EP.

Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. 

Molecular and Cellular Biology January, 2006, 26(2):654-667.

8)  Nierhoff D, Ogawa A, Oertel M, Chen YC, Shafritz DA.

Characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity.

Hepatology, 2005, Jul; 42(1):130-9.

9) Sachinidis A, Gissel C, Nierhoff D, Hippler-Altenburg R, Sauer H, Wartenberg M and Hescheler J.

Identification of plateled-derived growth factor-BB as cardiogenesis-inducing factor in mouse embryonic stem cells under serum-free conditions.

Cellular Physiology and Biochemistry, 2003, 13:423-429.

10)  Nierhoff D, Horvath HC, Mytilineos J, Golling M, Bud O, Klar E, Opelz G, Voso MT, Ho AD, Haas R and Hohaus S.

Microchimerism in bone marrow-derived CD34+ cells of patients after liver transplantation.

Blood, 2000, July 15; 96(2): 763-767