The major aim of the work in our research group is to understand tumor heterogeneity and its role in drug resistance as well as stratification of patients.
Tumors evolve by acquiring different clonal populations with unique genomic and epigenomic characteristics. The resulting biological and molecular complexity is manifested in tumor biology such as metastasis and recurrence. This tumor heterogeneity is a major cause why patients fail to respond to therapy, and particularly is an issue in the mamagement of hepatobiliary cancers, where patient stratification is still to enter clinical practise.
Disease focus: Primary human hepatobiliary and pancreatic cancers
To achieve our aim, we focus on genomics- and epigenomics-driven translational medicine with an emphasis on patient stratification and characterization, and prognostic or predictive biomarker discovery, to aid novel therapeutics and clinical efficacy.
1. Characterization of the genetic variants in hepatobiliary cancers as well as determine the consequence of structural variance on treatment.
Tumor heterogeneity is not merely a concern of variability between individual tumors but more so within a tumor itself. The presence of dormant and drug resistant clones within a tumor may lead to tumor recurrence, spread and challenge therapy. Therefore, it is important to understand the pathobiology and genomic characteristics at a cellular level.
2. Identify the changes in the epigenome, which affect hepatobiliary cancer development and how these aberrations integrate with e.g., the transcriptome to determine the disease phenotype and response to therapy.
We unite research directly on patient samples and clinicopathological data with basic molecular in vitro and in vivo models. We encourage a very interdisciplinary collaborative environment with a joined aim to improve therapeutics and advance patient outcome.
Single cell genomics
Integrative (cross-species) - omics
Liver Cancer Oncogenomics: Opportunities and Dilemma for Clinical Applications. Marquardt JU & Andersen JB (2015). Future Medicine (Hepatic oncology) Jan 201Vol2(1) in press
Impact of microenvironment and stem-like plasticity in Cholangiocarcinoma: Molecular network and biological concepts. Raggi C, Invernizzi P and Andersen JB (2014). Journal of Hepatology Sep 11.
Molecular Pathology of Intrahepatic Cholangiocarcinoma. Andersen JB (2014). Journal Hepatobiliary and Pancreatic Science (Special Issue) Sep 1.
P53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer. Tschaharganeh DF, Xue W, Calvisi DF, Evert M, Michurina T, Dow L, Banito A, Katz S, Kastenhuber E, Weismueller S, Lechel A, Andersen JB, Capper D, Zender L, Longerich T, Enikolopov G and Lowe SW (2014). Cell Jul 31;158(3):579-92.
Sequential analysis of hepatocarcinogenesis indicates late stage acquisition of malignant traits. Marquardt JU$, Seo D$, Andersen JB$, Gillen MC, Kim MS, Conner EA, Factor VM, Park YN and Thorgeirsson SS (2014). Journal of Hepatology Feb 60(2):346-53. $Authors contributed equally.
Modelling Pathogenesis of Primary Liver Cancer in Lineage-Specific Mouse Cell Types. Holczbauer A, Factor VM, Andersen JB, Marquardt JU, Kleiner D, Raggi C, Kitade M, Seo D, Hirofumi A, Durkin M and Thorgeirsson SS (2013). Gastroenterology Jul 145(1):221-31
Genomic and Genetic Characterization of Cholangiocarcinoma Identify Therapeutic Options for Tyrosine Kinase Inhibitors. Andersen JB, Spee B, Blechacz BR, Avital I, Komuta M, Barbour A, Conner EA, Gillen MC, Roskams T, Roberts LR, Factor VM and Thorgeirsson SS (2012). Gastroenterology Apr;142(4):1021-1031
mTOR inhibitors synergize on regression, reversal of gene expression and autophagy in hepatocellular carcinoma. Hala ET, Mercer MA, Carnevalli LS, Park J, Andersen JB, Conner EA, Tanaka K, Matsutani T, Iwanami A, Aronow BJ, Manway L, Thorgeirsson SS, Mischel PS, Thomas G and Kozma SC (2012). Science Translational Medicine Jun 20;4(139).