Andersen Group

The main goal of our research is to gain an understanding of the molecular pathogenesis leading to primary liver cancers. We aim to unravel the underlying biological mechanisms that are required for the tumor to grow, to evade diagnosis (silent) until late stage where the tumor is either locally advanced or metastatic, and to utilize genome-wide approaches in patient characterization and stratification to facilitate precision therapy.

Disease focus


Image 1: The Andersen group is an interdisciplinary research laboratory focused on malignancies related to the liver and biliary system (Click here to view larger image).

With the realization that these malignancies are a highly heterogenous and a molecularly complex group of diseases, we focus on the patient in an interdisciplinary team jointly aiming at improving the clinical outcome. To achieve our goal, we leverage genome-wide data and systems approaches to model disease causality, which will be used in stratifying patients for advancing diagnostic and prognostic markers as well as to aid novel therapeutics and clinical efficacy.

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 joint aim to improve therapeutics and advance patient outcome.

Approach

Image 2: Translational medicine and systems biology approaches applied in the group (Click here to view larger image).

Technology in our laboratory spans broadly genomic and epigenomic characterization, functional high-throughput screens to elucidate disease-relevant genes and drug resistant mechanisms as well as disease-modelling in primary cultures and mice over diagnostic or metabolic rearrangement in the early onset of liver disease.

What we do

Image 3: Research approaches used in the group to understand molecular pathogenesis of hepatobiliary malignancies (Click here to view larger image).

Project themes

  1. Understanding the molecular pathogenesis of hepatobiliary cancers. Despite tantalizing clues as to the importance of genetics in hepatobiliary carcinogenesis, little is known about the genetic underpinnings of these malignancies. In this program, our primary goal is to characterize the molecular alterations important in intrahepatic and extrahepatic bile duct cancers, leveraging a multi-omics approach to emphasize patient subset for precision therapy.
  1. Characterizing the deregulated epigenomic control in metastasis and guiding treatment. Epigenetic alterations ‘epimutations’ comprise alternative genomic perturbation mechanisms, the dynamic nature of which may present rapid tumor diversification during disease progression. We know primary liver cancers are highly polarized at the epigenomic level both in the primary and metastatic stages of the disease. This suggests a fundamental difference in their molecular pathogenesis, which may be exploited therapeutically (epi-therapy).
  1. Understanding the early metabolic rearrangements in the liver. The endemic increase in obesity promotes Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH), which affect up to 40% of the European population. The liver is a key organ in controlling metabolic homeostasis, and rearrangements in these processes are known to cause HCC. However, the exact alterations causing metabolic disease to progress to HCC remain elusive. Manipulation of central genes controlling the metabolic imbalance will allow us to understand the biology and consequence in HCC progression. This knowledge is crucial to improve diagnosis, patient stratification and design novel treatment options.
  1. Utilizing non-coding RNAs in biomarker discovery and drug resistance. To elucidate the role of microRNAs in diagnosis, prognosis and in controlling treatment resistant mechanisms (compensatory mechanisms).

Keywords:

Translational medicine
Tumor heterogeneity
Drug resistance
Integromics
Functional genomics
Epigenomics-drive therapy
Metabolic disease

Selected Publications:

Identification of a pan-gamma-secretase inhibitor response signature for notch-driven cholangiocarcinoma. O'Rourke CJ, Matter MS, Nepal C, Caetano-Oliveira R, Ton PT, Factor VM, Andersen JB. Hepatology. 2019 Jun 18. PMID:31211856

Epigenome Remodeling in Cholangiocarcinoma. O'Rourke CJ, Lafuente-Barquero J, Andersen JB. Trends in Cancer. 2019 Jun;5(6):335-350. Review. PMID:31208696

Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma. Nepal C, O'Rourke CJ, Oliveira DVNP, Taranta A, Shema S, Gautam P, Calderaro J, Barbour A, Raggi C, Wennerberg K, Wang XW, Lautem A, Roberts LR, Andersen JB. Hepatology. 2018 Sep;68(3):949-963. PMID:29278425

Desmoplastic Tumor Microenvironment and Immunotherapy in Cholangiocarcinoma. Høgdall D, Lewinska M, Andersen JB. Trends in Cancer. 2018 Mar;4(3):239-255. Review. PMID:29506673

MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma. Lampis A, Carotenuto P, Vlachogiannis G, Cascione L, Hedayat S, Burke R, Clarke P, Bosma E, Simbolo M, Scarpa A, Yu S, Cole R, Smyth E, Mateos JF, Begum R, Hezelova B, Eltahir Z, Wotherspoon A, Fotiadis N, Bali MA, Nepal C, Khan K, Stubbs M, Hahne JC, Gasparini P, Guzzardo V, Croce CM, Eccles S, Fassan M, Cunningham D, Andersen JB, Workman P, Valeri N, Braconi C. Gastroenterology. 2018 Mar;154(4):1066-1079. PMID:29113809

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. 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. PMID:28428144 

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. Nature Communications. 2017 Feb 21;8:14294. PMID:28220783