Experimental and Molecular Pathology – Focus HPB and GI Pathology

Experimental and Molecular Pathology – Focus: Molecular Hepatobiliary and Gastrointestinal Pathology, Group Achim Weber.

The University Hospital Zurich (USZ) has a major focus on diseases of the hepato-pancreato-biliary system and gastro-intestinal tract. The Swiss Hepato-Pancreato-Biliary (HPB) center and the ENTES (European neuroendocrine tumor society) center both are centers of excellence in Zurich for diseases of the liver, biliary tract and pancreas, and gastro-entero-pancreatic neuroendocrine (GEP-NET), respectively. A professorship was implemented in 2010 to cover the need of the University of Zurich (UZH) and the USZ in research and diagnostics in the field of liver, biliary tract, pancreas, and gastrointestinal pathology.

Clinical pathology, diagnostic team and diagnostic profile

Diagnostic Profile

The team covers the whole spectrum of diagnostic pathology in the field of liver, biliary tract, pancreas, and gastrointestinal pathology. A major focus is on diagnostic molecular pathology. Besides routine diagnostic cases, these fields comprise highly specialized works and activities, such as:

  • Surgical pathology and molecular testing of cases within the Swiss Hepato-Pancreato-Biliary (HPB) center
  • Surgical pathology of neuroendocrine tumors (NET Board)
  • Molecular diagnostic of hereditary cancer syndromes including genetic testing (MEN1, MEN2, SDH, VHL)
  • Second opinion and outside consultant cases in these fields

Surgical pathology service is performed in close interaction with clinical partners within the USZ and outside. The following clinical conferences are held on a regular basis:

  1. Surgical-oncological (HPB) board (weekly)
  2. Surgical-oncological (GIT) board (weekly)
  3. Hepato-pathological conference (weekly)
  4. NET board (biweekly)
  5. Gastro-intestinal conferences (gastrointestinal clinics: USZ, Stadtspital Waid, Zürich, Spital Männedorf, GCZ – Gastro Club Zurich)

 

Research, team and research profile

Former Group Members

  • Bawohl Marion, Technician
  • Böhm Friederike, PhD, Postdoc
  • Böge Yannick, PhD, Student, PhD, Postdoc
  • Büehler Simone, Master student
  • Brack Ursula, Master Student
  • Comtesse Sarah, MD, Molecular Pathology resident
  • Frick Lukas, Master and Doctoral student
  • Heikenwälder Mathias, PhD, Professor, Academic Guest
  • Junyent Sallares Eva, MsC, intern
  • Maire Renaud, Technician
  • Maleh Mir Mohsen, PhD Student
  • Schmitt Johannes, PhD, Postdoc
  • Susanne Kreutzer, PhD Student
  • Wolf Monika, PhD, Postdoc

Research profile

The group has a focus on liver and intestinal carcinogenesis. These projects involve mouse models of diseases as well as analysis of human tissues. In addition to basic research projects, the group works on projects arising from routine diagnostic clinical and molecular pathology.

Research collaborations

The group has several intramural and external collaborations including:

  • Visceral Surgery (Pierre Alain Clavien, Rolf Graf), USZ, Zurich
  • Clinic for Gastroenterology and Hepatology (Beat Müllhaupt, Joachim Mertens, Gerhard Rogler, Michael Scharl), USZ, Zurich
  • Institute for Anesthesiology (Beatrice Beck-Schimmer), USZ, Zurich
  • Institute of Molecular Health Sciences (Sabine Werner), ETH Zurich
  • Institute of Virology (Matthias Heikenwälder, Ulrike Protzer), TU Munich, Germany
  • Institute of Pathology (Peter Schirmacher, Kai Breuhan, Thomas Longerich), University Heidelberg, Germany
  • Institute of Pathology (Erik Springer), University Mainz, Germany

Funding

Since 2010, external funding has been provided by the following organizations

  • Krebsliga Schweiz (KLS, Oncosuisse)
  • Swiss National Research Foundation (SNF)
  • Promedica Stiftung, Chur
  • Krebsliga Zürich (KLZH)
  • Julius Müller Stiftung zur Unterstützung der Krebsforschung, Zurich
  • Stiftung zur Krebsbekämpfung, Zürich
  • Theiler-Haag Stiftung, Zürich

Master and Doctoral Thesis

The group offers Master and Doctoral thesis in the field of liver and gastrointestinal pathology with both, a basic research focus or a clinically oriented. Candidates interested may contact us.

Open Positions

Candidates interested may contact us.

  • Berger E, Rath E, Detian Y, Waldschmitt N, Khaloian S, Allgäuer M, Staszewski O, Lobner EM, Schöttl T, Giesbertz P, Coleman OI, Prinz M, Weber A, Gerhard M, Klingenspor M, Janssen KP, Heikenwalder M, Haller D
    Mitochondrial function controls intestinal epithelial stemness and proliferation
    Nature Communications 2016 7:13171
    Impact factor (journal citation report 2015):   11.329
  • Finan, B., Clemmensen, C., Zhu, Z., Stemmer, K., Gauthier, K., Müler, L., de Angelis, M., Moreth, K., Neff, F., Perez-Tilve, D., Fischer, K., Lutter, D., Sanches-Garrido, M.A., Liu, P., Healy, M. E., Malehmir, M., Weber, A., Heikenwälder, M., Jastroch, M., Kleinert, M., Brandt, S., Flamant, F., Schramm, K., Biebermann, H., Döring, Y., Weber, C., Habegger, K.M., Keuper, M., Gelfanov, V., Liu, F., Köhrle, J., Rozman, J., Fuchs, H., Gailus-Durner V, Hrabe de Angelis, M., Hofmann, S.M., Yang, B., Tschöp, MH., Di Marchi, R., Müller, T.D.
    Selective targeting of T3 via glucagon transport offers precision metabolic therapy without thyrotoxicity
    Cell 2016 167(3):843-857
    Impact factor (journal citation report 2015): 28.71
  • Sacré A, Lanthier N, Dano H, Aydin S, Leggenhager D, Weber A, Dekairelle AF, De Cuyper A, Gala JL, Humblet Y, Sempoux C, van den Eyde M
    Regorafenib induced severe toxic hepatitis: characterization and discussion
    Liver International 2016 doi: 10.1111/liv.13217. [Epub ahead of print]
    Impact factor (journal citation report 2015): 4.71
  • Koppe C, Verheugd P, Gautheron J, Reisinger F, Kreggenwinkel K, Roderburg C, Quagliata L, Terracciano L, Gassler N, Tolba RH, Boege Y, Weber A, Karin M, Luedde M, Neumann UP, Weiskirchen R, Tacke F, Vucur M, Trautwein C, Lüscher B, Preisinger C, Heikenwalder M, Luedde T
    IKKα/β control biliary homeostasis and hepatocarcinogenesis in mice by phosphorylating the cell-death mediator RIPK1
    Hepatology 2016 64(4):1217-31
    Impact factor (journal citation report 2014):   11.055
  • Scherr AL, Gdynia G, Salou M, Radhakrishnan P, Duglova K, Heller A, Keim S, Kautz N, Jassowicz A, Elssner C, HE YW, Jaeger D, Heikenwalder M, Schneider M, Weber A, Roth W, Schulze-Bergkamen H, Köhler B
    Bcl-xL is an oncogenic driver in colorectal cancer
    Cell Death Dis 2016 7(8):e2342
    Impact factor (journal citation report 2014):   5.014
  • Ma C, Kesarwala AH, Eggert T, Medina-Echeverz J, Kleiner DE, Jin P, Stroncek DF, Terabe M, Kapoor V, ElGindi M, Han M, Thornton AM, Zhang H, Egger M, Luo J, Felsher DW, McVicar DW, Weber A, Heikenwalder M, Greten TF
    NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis
    Nature 2016 531(7593):253-7
    Impact factor (journal citation report 2014):   41.456
  • Matter MS, Marquardt JU, Andersen JB, Quintavalle C, Korokhov N, Stauffer JK, Kaji K, Decaens T, Quagliata L, Elloumi F, Hoang T, Molinolo A, Conner EA, Weber A, Heikenwalder M, Factor VM, Thorgeirsson SS
    Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype
    Hepatology 2016 Epub ahead of print
    Impact factor (journal citation report 2014):   11.055
  • Tschuor C, Kachaylo E, Perparim L, Raptis DA, Linecker M, Tian Y, Herrmann U, Grabliauskaite K, Weber A, Columbano A, Graf R, Humar B*, Clavien PA*
    Car-driven regeneration protects liver from failure following tissue loss and bears therapeutic potential
    Journal of Hepatology 2016 [Epub ahead of print]
    Impact factor (journal citation report 2014):   11.336
  • Meier R, Lutz C, Cosín-Roger J, Fagagnini S, Bollmann G, Hünerwadel A, Mamie C, Lang S, Tchouboukov A, Weber FE, Weber A, Rogler G, Hausmann M
    Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis
    Inflamm Bowel Dis 2016 22(3):569-82
    Impact factor (journal citation report 2014):   4.464
  • Mertz KD*, Mager LF*, Wasmer MH, Thiesler T, Koelzer VH, Ruzzante G, Joller S, Murdoch JR, Brümmendorf T, Gentisch V, Lugli A, Cathomas G, Moch H, Weber A, Zlobec I, Junt T, Krebs P
    The 1 IL-33/ST2 pathway contributes to intestinal tumorigenesis in humans and mice
    Oncoimmunology 2016 26;5(1):e1062966. eCollection
    Impact factor (journal citation report 2014):   6.266
  • Weber A, Heikenwalder M
    P(URI)fying novel drivers of NASH and HCC: A feed-forward loop of IL17A via white adipose tissue
    Cancer Cell 2016 30(1):15-7
    Impact factor (journal citation report 2014): 23.523
  • Koelzer VH, Glatz K, Weber A, Flatz L, Cathomas G, Zippelius A, Mertz KD
    Wirkungen und Nebenwirkungen der Tumor-Immuntherapie
    SWISS MEDICAL FORUM – SCHWEIZERISCHES MEDIZIN-FORUM 2016;16(51–52):1113–1115
    Impact factor (journal citation report 2015):   2.086
  • Köhler UA, Böhm F, Rolfs F, Egger M, Hornemann T, Pasparakis M,  Weber A*#, Werner S*#
    NF-κB/RelA and Nrf2 cooperate to maintain hepatocyte integrity and to prevent development of hepatocellular adenoma
    Journal of Hepatology 2015 [Epub ahead of print]
    Impact factor (journal citation report 2014): 11.336
    *co-last authors, #co-corresponding authors
  • Tschuor C, Kachaylo E, Perparim L, Raptis DA, Linecker M, Tian Y, Herrmann U, Grabliauskaite K, Weber A, Columbano A, Graf R, Humar B, Clavien PA
    Car-driven regeneration protects liver from failure following tissue loss and bears therapeutic potential
    Journal of Hepatology 2015 (accepted)
    Impact factor (journal citation report 2014): 11.336
  • Garnelo M, Tan A, Her Z, Yeong J, Lim CJ, Chen J, Lim KH, Weber A, Chow P, Chung A, Ooi LLPJ, Toh HC, Heikenwalder M, Ng IOL, Nardin A, Chen Q, Abastado JP, Chew V
    Interaction between tumor-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma
    Gut 2015 accepted
    Impact factor (journal citation report 2014): 14.66
  • Weber A, O’Connor, Heikenwalder M
    Next generation of pre-clinical liver cancer models
    Clinical Cancer Research 2015
    Impact factor (journal citation report 2014): 8.722
  • Mu X, Espanol-Suner R, Mederacke I, Manco R, Sempoux C, Affo S, Lemaigre FP, Adili A, Yuan D,  Weber A, Unger K, Heikenwalder M, Leclercq IA, Schwabe R
    Hepatocellular carcinoma originates from hepatocytes and not from progenitor cells
    Journal of Clinical Investigation 2015 125(10):3891-903
    Impact factor (journal citation report 2014): 13.215
  • Friemel J, Frick L, Weber A
    Intratumor heterogeneity in hepatocellular carcinoma
    Aging 2015 7(6):350-1
    Impact factor (journal citation report 2014): 6.432
  • Finkin S, Yuan D, Stein I, Taniguchi K, Weber A, Unger K, Browning JL,Goossens N, Nakagawa S, Gunasekaran G, Schwartz ME, Kobayashi M, Kumada H, Berger M, Pappo O, Rajewski K, Hoshida Y, Karin M, Heikenwalder M,  Ben-Neriah Y, Pikarsky E
    Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma
    Nature Immunology 2015 [Epub ahead of print]
    Impact factor (journal citation report 2014): 20.004
  • Chijioke O, Bawohl M, Springer E, Weber A
    Hepatitis E Virus Detection in Liver Tissue from Patients with Suspected Drug-Induced Liver Injury
    Frontiers in Medicine, Section Pathology 2015 2:20. doi: 10.3389
    Impact factor (journal citation report 2013): not yet defined
  • Protzer U, Böhm B, Longerich T, Seebach J, Navid MH, Friemel J, Marques-Maggio E, Bawohl M, Heikenwalder M, Schirmacher P, Dutkowski P, Clavien PA, Schemmer P, Schnitzler P, Gotthardt D, Müllhaupt B, Weber A
    Molecular detection of hepatitis E-virus (HEV) in liver biopsies after liver transplantation
    Modern Pathology 2015 28(4):523-32
    Impact factor (journal citation report 2013): 6.364
  • Friemel J, Rechsteiner M, Frick L, Böhm F, Struckmann K, Sigg  M, Moch H, Heikenwalder M, Weber A
    Intratumor heterogeneity in hepatocellular carcinoma
    Clinical Cancer Research 2015 21(8):1951-61
    Impact factor (journal citation report 2013): 8.193
    highlights of this issue: Implications for Tumor Classifications and Targeted Therapies Clinical Cancer Research 2015 21(8):1777
    editorial: Nault & Villanueva Intratumor Molecular and Phenotypic Diversity in Hepatocellular Carcinoma Clinical Cancer Research 2015 21(8):1786-88
  • Wolf MJ, Adili A, Piotrowitz K, Abdullah Z, Boege Y, Stemmer K, Ringelhan M, Simonavicius N, Egger M, Wohlleber D, Lorentzen A, Einer C, Schulz S, Clavel T, Protzer U, Thiele C, Zischka H, Moch H, Tschöp M, Tumanov AV, Haller D, Unger U, Karin M, Kopf M, Knolle P*, Weber A*#, Heikenwalder M*#
    *co-last authors, #co-corresponding authors
    Metabolic activation of intrahepatic CD8+ and NKT-cells causes nonalcoholic steatohepatitis and hepatocellular carcinoma via cross-talk with hepatocytes
    Cancer Cell 2014 26(4):549-64
    Impact factor (journal citation report 2013): 23.893
    cover page of Cancer Cell, Volume 26, Issue 4 October 13, 2014: Feedfoward loop for NKT and CD8+ cells in NASH and HCC
  • Malz M, Bovet M, Samarin J, Rabenhorst U, Sticht C, Bissinger M, Roessler S, Lorenzo Bermejo J, Renner M, Calvisi DF, Singer S, Ganzinger M, Weber A, Gretz N, Zörnig M, Schirmacher P, Breuhahn K
    Overexpression of far upstream element (FUSE) binding protein (FBP)-interacting repressor (FIR) supports growth of hepatocellular carcinoma
    Hepatology 2014 60(4):1241-50
    Impact factor (journal citation report 2013): 11.19
  • Soldini D, Gaspert A, Montani M, Reineke T, Rogler G, Odze R, Weber A
    Apoptotic enteropathy caused by antimetabolites and TNF-α antagonists
    Journal of Clinical Pathology 2014 67(7):582-6
    Impact factor (journal citation report 2013): 2.551
  • Rickenbacher A, Jang JH, Limani P, Ungethüm U, Lehmann K, Oberkofler CE, Weber A, Graf R, Bostjan H*, Clavien PA*
    Fasting protects liver from ischemic injury through Sirt1-mediated downregulation of circulating Hmgb1 in mice
    Journal of Hepatology 2014 61(2):301-8
    Impact factor (journal citation report 2013): 10.401
  • Weber A, Marques-Maggio E
    Apoptotic Colonopathy under Immunosuppression: Mycophenolate-Related Effects and Beyond
    Pathobiology 2013 80(6):282-8
    Impact factor (journal citation report 2013): 2.319
  • Vucur M, Reisinger F, Gautheron J, Janssen J, Roderburg C, Cardenas DV, Kreggenwinkel K, Koppe C, Hammerich L, Hakem R, Unger K, Weber A, Gassler N, Luedde M, Frey N, Neumann UP, Tacke F, Trautwein C, Heikenwalder M, Luedde T
    RIP3 inhibits inflammatory hepatocarcinogenesis but promotes cholestasis by controlling Caspase-8- and JNK-dependent compensatory cell proliferation
    Cell Reports 2013 4(4):776-90
    Impact factor (journal citation report 2013): 7.207
  • Spalinger MR, Lang S, Weber A, Frei P, Fried M, Rogler G, Scharl M
    Loss of Protein Tyrosine Phosphatase Non-Receptor Type 22 Regulates Interferon-γ-Induced Signaling in Human Monocytes
    Gastroenterology 2013 144(5):978-988
    Impact factor (journal citation report 2013): 13.926
  • Lehmann K, Tschuor C, Rickenbacher A, Jang JH, Oberkofler CE, Tschopp O, Schulze S, Raptis DA, Weber A, Graf R, Humar B, Clavien PA
    Liver Failure after Extended Hepatectomy in Mice is Mediated by a p21-Dependent Barrier to Liver Regeneration
    Gastroenterology 2012 143(6):1609-1619
    Impact factor (journal citation report 2012): 12.821
  • Wolf MJ, Hoos A, Bauer J, Boettcher S, Knust M, Weber A, Simonavicius N, Schneider C, Lang M, Stürzl M, Croner RS, Konrad A, Manz MG, Moch H, Aguzzi A, van Loo G, Pasparakis M, Prinz M, Borsig L, Heikenwalder M
    Endothelial CCR2 signaling induced by colon carcinoma cells enables extravasation via the JAK2-Stat5 and p38MAPK pathway
    Cancer Cell 2012 22(1):91-105
    Impact factor (journal citation report 2012): 24.755
  • Chew V, Chen J, Lee D, Loh E, Lee J, Lim KH, Weber A, Slankamenac K, Poon RT, Yang H, Ooi LL, Toh HC, Heikenwalder M, Ng IO, Nardin A, Abastado JP
    Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma
    J Nat Cancer I 2012 104(23):1796-807
    Impact factor (journal citation report 2012): 14.336
  • Jang JH, Rickenbacher A, Humar B, Weber A, Raptis DA, Lehmann K, Stieger B, Moritz W, Soll C, Georgiev P, Fischer D, Laczko E, Graf R, Clavien PA
    Serotonin protects mouse liver from cholestatic injury by decreasing bile salt pool after bile duct ligation
    Hepatology 2012 56(1):209-18
    Impact factor (journal citation report 2012): 12.003
  • Raptis DA, Fischer MA, Graf R, Nanz D, Weber A, Moritz W, Tian Y, Oberkofler CE, Clavien PA
    Resonance Imaging: The new reference standard in quantifying hepatic steatosis?
    Gut 2012 61(1):117-27
    Impact factor (journal citation report 2012): 10.732
  • Chew V, Chen J, Lee D, Loh E, Lee J, Lim KH, Weber A, Slankamenac K, Poon RT, Yang H, Ooi LL, Toh HC, Heikenwalder M, Ng IO, Nardin A, Abastado JP
    Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma
    Gut 2012 61(3):427-38
    Impact factor (journal citation report 2012): 10.732
  • Brauckhoff A*, Malz M*, Tschaharganeh D, Malek N, Weber A, Riener MO, Soll S, Bissinger M,  Schmidt J, Longerich T, Ehemann V, Schirmacher P, Breuhahn K
    Nuclear expression of the ubiquitin ligase seven in absentia homologue (SIAH)-1 induces proliferation and migration of liver cancer cells
    J Hepatology 2011 55(5):1049-57
    Impact factor (journal citation report 2012): 9.858
  • Scharl M, McCole DF, Weber A, Vavricka SR, Frei P, Kellermeier S, Pesch T, Fried M, Rogler G
    Protein tyrosine phosphatase N2 regulates TNF{alpha}-induced signalling and cytokine secretion in human intestinal epithelial cells
    Gut 2011 60(2):189-97
    Impact factor (journal citation report 2012): 10.732
  • Ikenberg K, Springer E, Bräuninger W, Kerl K, Mihic D, Schmid S, Schmitt A, Yeginsoy S, Bode B, Weber A
    Oropharyngeal lesions and cervical lymphadenopathy: syphilis is a differential diagnosis that is still relevant
    J Clin Pathol 2010 63(8):731-6.
    Impact factor (journal citation report 2012): 2.439
  • Bettermann K, Vucur M, Koppe C, Heymann F, Haybaeck J, Weber A, Weiskirchen R, Liedtke C, Gassler N, Müller M, Akira S, Tacke F, Heikenwalder M, Trautwein C, Luedde T
    TAK1 suppresses a NEMO-dependent, but NF-B independent pathway to liver cancer
    Cancer Cell 2010 17:481-496
    Impact factor (journal citation report 2012): 24.755
  • Weber A*, Boger R*, Vick B, Urbanik T, Haybaeck J, Zoller S, Teufel A, Krammer PH, Opferman JT, Galle PR, Schuchmann M, Heikenwalder M, Schulze-Bergkamen H
    Hepatocyte-specific deletion of the anti-apoptotic protein Mcl-1 triggers proliferation and hepatocarcinogenesis in mice
    Hepatology 2010 51(4):1226-36
    Impact factor (journal citation report 2012): 12.003
    editorial: Jost  & Kaufmann  Cancer caused by too much apoptosis–an intriguing contradiction?
    Hepatology 2010 51(4):1110-12
  • Weber A, Chung JH, Springer E, Heitzmann D, Warth R
    The TFIIH subunit p89 (XPB) localizes to the centrosome during mitosis
    Cellular Oncology 2010 32:121-130
    Impact factor (journal citation report 2010): 3.175

Contact

Achim Weber, Prof. Dr. med.

Leitender Arzt, Stv. Institutsdirektor, Institut für Pathologie und Molekularpathologie

Tel. +41 44 255 27 81
Spezialgebiete: Molekularpathologie, Gastrointestinale Pathologie, Leberpathologie