Andersen Group

The goal of the laboratory is to unravel the biological mechanisms leading to primary liver and biliary tract cancers and thus, understand the molecular pathogenesis. Our ambition is to translate solutions to the clinic for improved patient outcome.

The Andersen group is an interdisciplinary research laboratory focused on malignancies related to the liver and biliary system
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 1).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1. NAFLD-HCC.

Lewinska M et al. EBioMedicine, 2021. The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) is a group of metabolic disorders that can progress to hepatocellular carcinoma (HCC) often without a background of cirrhosis. NAFLD is known to affect 24% of the global population. Liver cancers, developing in the background of NAFLD is on the rise. In this study, we show:

  • The first comprehensive serum lipidomics investigating a broad-range of lipid classes in NAFLD and NAFLD-HCC
  • Evidence of lipidomics in detection of NAFLD-HCC. We have developed a NAFLD-HCC Diagnostic Score (NHDS) as a putative screening tool for HCC development in a metabolic liver background
  • How fatty acid (FA) uptake is increased in NAFLD-HCC tumors, which result in FA depletion in the blood circulation of NAFLD-HCC patients

2. Integrative molecular characterization of gallbladder cancer (GBC) reveals microenvironment-associated subtypes

Nepal, Zhu & O’Rourke et al. Journal of Hepatology, 2020. Integrative molecular characterization of gallbladder cancer (GBC) reveals microenvironment-associated subtypes

Gallbladder cancer is highly fatal, and its causes are poorly understood. 

  • We found evidence of aflatoxin exposure in GBC based on an aflatoxin-related genetic signature. Aflatoxins are a family of toxins produced by certain fungi that grow on agricultural crops such as corn and peanuts. Out of 92 patients with GBC, 39 (42%) had the aflatoxin-related signature, and these mutations tended to be clonal present in more than 50% of the cancer cells, suggesting that aflatoxin exposure resulted in early molecular changes.
  • Immune cells surrounding the tumors (tumor microenvironment) were associated with survival

3. BTC: Serum IL-6 as a prognostic biomarker and therapeutic target.

Hogdall et al. Clinical Cancer Research, 2020. Serum IL-6 as a prognostic biomarker and IL-6R as a therapeutic target in biliary tract cancers

Biliary tract cancer (BTC) patients typically survive less than one year on standard-of-care chemotherapy. Adapting prognostic biomarkers to guide BTC patient management remains challenging. In this study, we measured serum IL-6, YKL-40, and CA19-9 before and during chemotherapy in 452 advanced BTC patients.

  • While all markers provided variable prognostic information prior to treatment, longitudinal analysis of IL-6 was superior in predicting death during treatment.
  • Blocking IL-6 (IL-6 receptor) signalling with tocilizumab significantly increased response to gemcitabine in a mouse model of human BTC.
  • Thus, the IL-6 axis may be prognostically informative and therapeutically attractive in this rare patient demographic.

5. Theranostic response signature defining NOTCH-driven cholangiocarcinoma.

O’Rourke et al. Hepatology, 2019. Identification of a pan-gamma-secretase inhibitor response signature for notch-driven cholangiocarcinoma.
Patent pending.

6. Novel integrative genomic strategy to stratify intrahepatic cholangiocarcinoma patients.

Nepal et al. Hepatology, 2017. Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma.

 

 

 

 

 

 

 

 

 

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.

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

Inflammatory niche controlled by IL6 promotes liver cancers. As cancer therapies advance, the duration and diversity of treatments are increasing per patient, extending the impact of systemic inflammation and requiring inflammation-directed therapies to impede treatment resistance and mitigate toxicities. In 410 Danish biliary tract cancer (BTC) patients, we have recently shown that serum levels of the cytokine, interleukin-6 (IL6), prior to and particularly during chemotherapy are associated with poor prognosis (read more about serum IL6 as a prognostic biomarker). Therefore, chronic IL6 signaling may result in de novo tumor behavior and therapeutic sensitivities, characterization of which can be exploited to develop new predictive biomarkers and drug combinations to target cancer-promoting inflammation and increase survival of cancer patients.

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.

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).

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.

Utilizing non-coding RNAs in biomarker discovery and drug resistance. To elucidate the role of ncRNAs in diagnosis, prognosis and in controlling treatment resistant mechanisms.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Selected publications

The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma. Lewinska M, Santos-Laso A, Arretxe E, Alonso C, Zhuravleva E, Jimenez-Agüero R, Eizaguirre E, Pareja MJ, Romero-Gómez M, Jimenez MA, Suppli MP, Knop FK, Oversoe SK, Villadsen GE, Decaens T, Carrilho FJ, de Oliveira CP, Sangro B, Macias RIR, Banales JM, Andersen JB. EBioMedicine. 2021 Oct 28;73:103661. doi: 10.1016/j.ebiom.2021.103661. Online ahead of print. PMID: 34740106 Fr

Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes. Nepal C, Zhu B, O'Rourke CJ, Bhatt DK, Lee D, Song L, Wang D, Van Dyke AL, Choo-Wosoba H, Liu Z, Hildesheim A, Goldstein AM, Dean M, LaFuente-Barquero J, Lawrence S, Mutreja K, Olanich ME, Lorenzo Bermejo J; CGR Exome Studies Group, Ferreccio C, Roa JC, Rashid A, Hsing AW, Gao YT, Chanock SJ, Araya JC, Andersen JB, Koshiol J. J Hepatol. 2021 May;74(5):1132-1144. doi: 10.1016/j.jhep.2020.11.033. Epub 2020 Dec 1. PMID: 33276026

Serum IL6 as a Prognostic Biomarker and IL6R as a Therapeutic Target in Biliary Tract Cancers. Høgdall D, O'Rourke CJ, Dehlendorff C, Larsen OF, Jensen LH, Johansen AZ, Dang H, Factor VM, Grunnet M, Mau-Sørensen M, Oliveira DVNP, Linnemann D, Boisen MK, Wang XW, Johansen JS, Andersen JB. Clin Cancer Res. 2020 Nov 1;26(21):5655-5667. doi: 10.1158/1078-0432.CCR-19-2700. Epub 2020 Sep 15. PMID: 32933994

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

View all publications

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

News from Andersen group

June 2021

iMED PhD student Lea Duwe to give an oral presentation titled “MicroRNA-27a-3p modulates FoxO1 to induce tumor-like phenotypes in the bile ducts” in the session “Liver Tumors Experimental and Pathophysiology” at The International Liver Congress 2021 (EASL).

Jesper B Andersen to give an educational seminar on oncogenomics in cholangiocarcinoma at the Copenhagen University Hospital, Department of Oncology.

Jesper B Andersen to present at the National Cancer Institute (NCI), Center for Cancer Research Liver cancer Program (LCP), NIH.

May 2021

Jesper B Andersen to co-organize and speak at the ILCA School on Liver Cancer 2021 hosted at Aarhus University Hospital

Yuewan Luo receives 3-year postdoc fellowship from the Lundbeck Foundation.

Jesper B Andersen to host the joint working group 2 (histopathology) and 3 (genomics) meeting under the Euro-CholangioNET COST Action.

April 2021

Colm J O’Rourke to present “Whole-transcriptome profiling of biopsies from unresectable intrahepatic cholangiocarcinoma (iCCA) reveals a prognostic signature with treatment implications” at the Cholangiocarcinoma Foundation Annual meeting.
This UK-Danish study is a collaboration between the Andersen group and Prof. Chiara Braconi, Glasgow University, UK.

Jesper B Andersen to chair session at the Cholangiocarcinoma Foundation Annual meeting in Salt Lake City.

March 2021

Jesper B Andersen to speak at the virtual keystone meeting: Hepatobiliary cancers: Pathobiology and Translational Advances

Jesper B Andersen to present at the COST Action EURO-CHOLANGIO-NET Training School in novel experimental models for cholangiocarcinoma: from ex-vivo patients derived organoids to in vivo animal models

Colm J O’Rourke to present a virtual tour of the project “Whole-transcriptome profiling of biopsies from unresectable intrahepatic cholangiocarcinoma (iCCA) reveals a prognostic signature with treatment implications”.
At the Liver Cancer Summit 2021. This UK-Danish study is a collaboration between the Andersen group and Prof. Chiara Braconi, Glasgow University. 09.02.2021

Jesper B Andersen to chair the session “Role of the microenvironment in cholangiocarcinoma” at the Liver Cancer Summit 2021. 09.02.2021

New paper by Nepal, Zhu & O’Rourke et al. in Journal of Hepatology. 04.12.2020

New paper by Dr. Dan Høgdall in Clinical Cancer Research. 17.09.2020

In the media

Mikromiljø omkring tumor afgørende for udvikling af galdeblærekræft

 16.12.2020 by Diagnostisk Tidsskrift

IL6-markør kan optimere beslutningsproces ved galdevejskræft

20.10.2020 by Diagnostisk Tidsskrift

Biomarker reveals how aggressive biliary tract cancer is in patients

15.09.2020 by BRIC

Early detection can help to defeat a deadly type of cancer

09.05.2020 by Science News

Biological plumbing: how the body makes ducts

10.12.2019 by Science News

Epigenetics: the Achilles heel of bile duct cancer?

07.06.2019 by CORDIS

Ny viden om kræft i galdevejene

11.01.2018 by Danish Cancer Society

Prizes, Honors and Awards

Monika Lewinska: International Liver cancer Association (ILCA) Junior Investigator Award for Basic and Translational Research, 2020

Colm J O’Rourke: International Liver Cancer Association (ILCA) Junior Investigator Award for basic and translational research, 2019, for Colm J O’Rourke.

Patricia Munoz-Garrido: European Association for the Study of the Liver (EASL) Sheila Sherlock Postdoc Fellowship, 2016, for Patricia Munoz-Garrido.

Chirag Nepal: International Liver Cancer Association (ILCA) Junior Investigator Award for basic and translational research, 2015, for Chirag Nepal.

Jesper B Andersen: Danish Cancer Society Merit Award for Achievements in Cancer Research, 2015, for Jesper Andersen .

Jesper B Andersen: Novo Nordisk Foundation Hallas Møller Investigator Award, 2015, for Jesper Andersen.

View Andersen Group on Twitter

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Jesper Andersen has helped develop the following info videos for CCA patients and their relatives. The videos are made in collaboration with Global Cholangiocarcinoma Alliance

  1. Disease overview
  2. Causes
  3. Signs and symptoms

 Further information

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CURRENT

NEYE logo

NEYE-FOUNDATION

Novonordisk fonden logo

NOVO NORDISK Foundation Hallas Møller award

Sapere Aude logo

FSS Sapere Aude 2

Lundbeck foundation logo

Lundbeck Foundation Individual postdoc fellowship

Danish Cancer Society logo

Danish Cancer Society Merit award for Cancer Research, Knæk Cancer, Project funding

EASL logo

European Association for the
Study of the Liver (EASL): Sheila Sherlock Postdoc fellowship

Horizon 2020 logo Marie Curie: Individual postdoc fellowships
Dansk kræftforenings fond logoDANSK KRÆFTFORSKNINGS FOND Dansk Kræftforskningsfond: Project

PAST FUNDING

AP Møller fonden

AP Møller Fonden: Technology grant

COLLABORATIVE FUNDING

No logo available Arvid Nilssons Fond: project
Lundbeck foundation logo

The Lundbeck Foundation: Individual PhD fellowship

Roche logo Roche Denmark A/S: Project
Beckett fonden logo

Beckett Fonden: Project

Herlev hospital logo

Herlev Hospitals forskningsfond & Capital Region: MD, PhD salary

Aase og Ejnar Danielsens fond logo

Aase og Ejnar Danielsens fond: project

No logo available

Fabrikant Ejner Willumsens mindelegat: Project