Andersen Group – University of Copenhagen

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Andersen Group

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

Image 1: Disease

 

Image 2. Translational genomics

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.

Image 3. Functional validation and patient stratification. Click to view larger image

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.

Image 4. Single cell genomics. Click to view larger image

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.

Keywords

Translational genomics
Tumor heterogeneity
Single cell genomics
Genomic-driven therapy
Epigenomic-driven therapy
Integrative (cross-species) - omics

Selected Publications

Epigenome dysregulation in cholangiocarcinoma.
O'Rourke CJ, Munoz-Garrido P, Aguayo EL, Andersen JB.
Biochim Biophys Acta. 2017 Jun 20. pii: S0925-4439(17)30209-0. doi: 10.1016/j.bbadis.2017.06.014. [Epub ahead of print] Review.
PMID:28645654 

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma.
Chaisaingmongkol J, Budhu A, Dang H, Rabibhadana S, Pupacdi B, Kwon SM, Forgues M, Pomyen Y, Bhudhisawasdi V, Lertprasertsuke N, Chotirosniramit A, Pairojkul C, Auewarakul CU, Sricharunrat T, Phornphutkul K, Sangrajrang S, Cam M, He P, Hewitt SM, Ylaya K, Wu X, Andersen JB, Thorgeirsson SS, Waterfall JJ, Zhu YJ, Walling J, Stevenson HS, Edelman D, Meltzer PS, Loffredo CA, Hama N, Shibata T, Wiltrout RH, Harris CC, Mahidol C, Ruchirawat M, Wang XW; TIGER-LC Consortium.
Cancer Cell. 2017 Jul 10;32(1):57-70.e3. doi: 10.1016/j.ccell.2017.05.009. Epub 2017 Jun 22.
PMID:28648284

Association of Aflatoxin and Gallbladder Cancer.
Koshiol J, Gao YT, Dean M, Egner P, Nepal C, Jones K, Wang B, Rashid A, Luo W, Van Dyke AL, Ferreccio C, Malasky M, Shen MC, Zhu B, Andersen JB, Hildesheim A, Hsing AW, Groopman J.
Gastroenterology. 2017 Aug;153(2):488-494.e1. doi: 10.1053/j.gastro.2017.04.005. Epub 2017 Apr 17.
PMID:28428144 

Genetic Optimization of Liver Cancer Therapy: A Patient-Derived Primary Cancer Cell-Based Model.
Munoz-Garrido P, Andersen JB.
Gastroenterology. 2017 Jan;152(1):19-21. doi: 10.1053/j.gastro.2016.11.030. Epub 2016 Nov 23. No abstract available.
PMID:27888667

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.
Farshidfar F, Zheng S, Gingras MC, Newton Y, Shih J, Robertson AG, Hinoue T, Hoadley KA, Gibb EA, Roszik J, Covington KR, Wu CC, Shinbrot E, Stransky N, Hegde A, Yang JD, Reznik E, Sadeghi S, Pedamallu CS, Ojesina AI, Hess JM, Auman JT, Rhie SK, Bowlby R, Borad MJ; Cancer Genome Atlas Network, Zhu AX, Stuart JM, Sander C, Akbani R, Cherniack AD, Deshpande V, Mounajjed T, Foo WC, Torbenson MS, Kleiner DE, Laird PW, Wheeler DA, McRee AJ, Bathe OF, Andersen JB, Bardeesy N, Roberts LR, Kwong LN.Cell Rep. 2017 Mar 14;18(11):2780-2794. doi: 10.1016/j.celrep.2017.02.033. Erratum in: Cell Rep. 2017 Jun 27;19(13):2878-2880.
PMID:28297679

An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer.
Vallejo A, Perurena N, Guruceaga E, Mazur PK, Martinez-Canarias S, Zandueta C, Valencia K, Arricibita A, Gwinn D, Sayles LC, Chuang CH, Guembe L, Bailey P, Chang DK, Biankin A, Ponz-Sarvise M, Andersen JB, Khatri P, Bozec A, Sweet-Cordero EA, Sage J, Lecanda F, Vicent S.
Nat Commun. 2017 Feb 21;8:14294. doi: 10.1038/ncomms14294.
PMID:28220783