Research Group Signalling - HCC

1) It has been known for more than one hundred years that there is a link between chronic inflammation and cancer development. Inflammatory bowel disease, especially ulcerative colitis is a risk factor for development of colorectal cancer. Chronic liver damage and liver cirrhosis caused by viral hepatitis B and C or alcoholic or non-alcoholic steatoheptitis lead to development of hepatocelluar carcinoma (HCC). More than 50 percent of all hepatocellular carcinomas develop as a result of chronic tissue damage caused by chronic inflammation.

In our research group we use transgenic, knock-out and chemical induced cancer mouse models

  • to develop new strategies for the treatment of liver cancer by inhibition of critical pathways by small molecule inhibitors, peptides, innovative viral vectors expressing shRNAs, combined targeting of cancer cells and tumor microenvironment, and improving tumor delivery of systemically administered drugs;
  • to develop new magnetic resonance imaging imaging techniques (e. g. nanoparticle contrast agents) to detect and follow the growth of murine HCC;
  • to elucidate critical regulators of inflammatory pathways for cancer development in the liver and the gut;
  • to discover new biomarkers for HCC.

2) As the diagnosis of hepatocelluar carcinoma (HCC) in the cirrhotic liver is still a challenge and only early detection of cancer can result in effective treatment like resection or liver transplantation we aim to investigate and validate new biomarkers for early HCC detection. Moreover, we examine diagnostic and prognostic markers in patients with liver cirrhosis and HCC in patient material.

3) Gs protein-coupled receptors are known to signal via the second messenger 3'-5'-cyclic adenosine monophosphate (cAMP) regulates diverse cell functions, e. g. cell proliferation, differentiation, apoptosis, cell-cell and cell-matrix interaction and migration and immune function. Classical effectors of cAMP are protein kinase A (PKA) and Epac1 and Epac2 (Exchange factor directly activated by cAMP). We are currently investigating novel signaling mechanisms of cAMP, in particular the interaction of cAMP and purinergic signaling.

 

Contact:

Prof. Dr. Dr. Albrecht Piiper

+49 69 6301 87667

Prof. Dr. Oliver Waidmann

+49 69 6301 87664

 

Group members

Dr. Tivdar Feczko (Humboldt Stipendium)Feczko@mukki.richem.hu

Dr.med. Fabian Finkelmeier Fabian.Finkelmeier@kgu.de

Bianca Kakoschky, MSc (PhD student) Kakoschky@med.uni-frankfurt.de

Prof. Dr. phil. nat. Dr. med. Albrecht Piiper (Group leader) Piiper@med.uni-frankfurt.de

Dr. rer. nat. Thomas Pleli (PostDoc) Pleli@med.uni-frankfurt.de

Dr. phil. nat. Christian Schmithals (PostDoc) Christian.schmithals@kgu.de

Prof. Dr. med. Oliver Waidmann (Group leader) Waidmann@biochem2.uni-frankfurt.de

 

 

Selected publications

Selected publications of the last 6 years

Bihrer V, Friedrich-Rust M, Kronenberger B, Haupenthal J, Forestier N, Shi Y, Peveling-Oberhag J, Radeke HH, Sarrazin C, Herrmann E, Zeuzem S, Waidmann O, Piiper A. Serum miR-122 as a biomarker of necroinflammatory activity in patients with chronic hepatitis C virus infection. AmJ Gastroenterol 2011;106, 1663-9

Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B, Korac J, Waidmann O, Choudhary C, Dötsch V, Bumann D, Dikic I. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 2011;333:228-33

Waidmann O, Bihrer V, Pleli T, Farnik H, Berger A, Zeuzem S, Kronenberger B, Piiper A. Serum microRNA-122 levels in different groups of patients with chronic hepatitis B virus infection. J Vir Hepat 2012;19, e58-65

Haupenthal J, Bihrer V, Korkusuz H, Kollmar O, Schmithals C., Kriener S, Engels K, Pleli T, Benz A, Canamero M, Longerich T, Kronenberger B, Waidmann O, Richter S, Vogl TJ, Zeuzem S, Piiper A. Reduced efficacy of the Plk1 inhibitor BI 2536 on the progression of hepatocellular carcinoma due to low intratumoral drug levels. Neoplasia 2012;14, 410-9

Kronenberger B, Rudloff I, Bachmann M, Brunner F, Kapper L, Fielmann N, Waidmann O, Herrmann E, Pfeilschifter J, Zeuzem S, Piiper A, Mühl H. Interleukin-22 predicts severity and death in advanced liver cirrhosis: A prospective cohort study. BMC Med 2012;10, 102

Korkusuz H, Ulbrich K, Welzel K, Koeberle V, Watcharin W, Chernikov V, Petersen S, Huebner F, Ackermann H, Gelperina S, Korkusuz Y, Kromen W, Hammerstingl R, Haupenthal J, Fiehler J, Vogl TJ, Kreuter J, Piiper A. Transferrin-coated gadolinium nanoparticles as MRI contrast agent. Mol Imaging Biol 2013;15, 148-54

Waidmann O, Brunner F, Herrmann E, Zeuzem S, Piiper A, Kronenberger B. Macrophage activation is a prognostic parameter for gastrointestinal bleeding and overall survival in patients with liver cirrhosis. J Hepatol 2013;58, 956–61

Waidmann O, Köberle V, Bettinger D, Trojan J, Zeuzem S, Schultheiß M, Kronenberger B, Piiper A.Diagnostic and prognostic significance of cell death and macrophage activation markers in patients with hepatocellular carcinoma. JHepatol 2013;59, 769-79

Köberle V, Kronenberger B, Pleli T, Trojan J, Peveling-Oberhag J, Welker MW, Elhendawy M, Imelmann E, Zeuzem S, Piiper A, Waidmann O. Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer 2013;49, 3442-9

Köberle V, Pleli T, Schmithals C, Augusto EA, Haupenthal J, BönigH, Peveling-Oberhag J, Biondi RM, Zeuzem S, Kronenberger B, Waidmann O, Piiper A. Differential stability of cell-free circulating microRNAs: Implications for their utilization as biomarkers. PLoS ONE 2013;8, e75184

Watcharin W, Schmithals C, Pleli T, Köberle V, Korkusuz H, Hübner F, Zeuzem S, Korf HW, Vogl T, Rittmeyer C, Terfort A, Piiper A, Gelperina S, Kreuter J. Biodegradable human serum albumin nanoparticles as contrast agents for the detection of hepatocellular carcinoma by magnetic resonance imaging. Eur J Pharm Biopharm 2014;87, 132–41

Finkelmeier F, Kronenberger B, Köberle V, Bojunga J, Zeuzem S, Trojan J, Piiper A, Waidmann O. Severe 25-hydroxyvitamin D deficiency identifies HCC patients with a poor prognosis. Aliment Pharmacol Ther 2014;39, 1204-12

Rosenberger I, Schmithals C, Vandooren J, Bianchessi S, Milani P, Locatelli E, Israel LL, Hübner F, Matteoli M, Lellouche JP, Franchini MC, Passoni L, Scanziani E, Opdenakker G, Piiper A, Kreuter J. Iron-containing albumin nanoparticles: a promising tool for medical imaging.