
Overview
Background
The Cancer Metabolism Group is keenly interested in how the physiological state of a person affects cancers.
Over a person’s lifetime, somatic cells will accumulate spontaneously occurring gene mutations, the majority of which do not cause disease. The global incidence of cancer has more than doubled over the past 30 years – primarily due to increasing living standards, modern lifestyles, and an aging population.
The common denominator for these is alterations to the physiological homeostasis of the individual at risk rather than a change in mutational burden. This strongly implies that the interaction of physiological conditions with cells harboring oncogenic mutations governs cancer risk.
The Cancer Metabolism lab utilizes systems biology technologies to both clinical biobank and mouse models to dissect the molecular drivers of the intersect between physiology and tumorigenesis.
Availability
- Dr Nils Henrik Halberg is:
- Available for supervision
- Media expert
Qualifications
- Doctor of Philosophy of Cell Metabolism, University of Copenhagen
Research interests
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Cancer cell plasticity
Cancer cells are adaptive. My key interest is how and why they adapt when exposed to physiological stressors as obesity, exercise and fasting.
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Cellular interaction networks
Wihtin the tumor ecosystems cells interact in niches. This might be closeness to blood vessels to support cellular functions or interacting with specific cells to enable adaption. Spatial technologies allow us to understand these at cellular resultion.
Research impacts
Key Publications
- C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer. Liu XZ, Rulina A, Choi MH, Pedersen L, Lepland J, Takle ST, Madeleine N, Peters SD, Wogsland CE, Grøndal SM, Lorens JB, Goodarzi H, Lønning PE, Knappskog S, Molven A, Halberg N. Nat Commun. 2022 Jan 10;13(1):69. doi: 10.1038/s41467-021-27734-2. PMID: 35013251
- High-dimensional immunotyping of tumors grown in obese and non-obese mice. Wogsland CE, Lien HE, Pedersen L, Hanjra P, Grondal SM, Brekken RA, Lorens JB, Halberg N. Dis Model Mech. 2021 Apr 1;14(4):dmm048977. doi: 10.1242/dmm.048977. Epub 2021 Mar 30. PMID: 33653826
- PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion. Halberg N, Sengelaub CA, Navrazhina K, Molina H, Uryu K, Tavazoie SF. Cancer Cell. 2016 Mar 14;29(3):339-353. doi: 10.1016/j.ccell.2016.02.013. PMID: 26977884
- Cellular mechanisms linking cancers to obesity. Liu XZ, Pedersen L, Halberg N. Cell Stress. 2021 Apr 12;5(5):55-72. doi: 10.15698/cst2021.05.248. PMID: 33987528
- A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Png KJ, Halberg N, Yoshida M, Tavazoie SF. Nature. 2011 Dec 14;481(7380):190-4. doi: 10.1038/nature10661. PMID: 22170610
- Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD, Sherwani S, Wang ZV, Landskroner-Eiger S, Dineen S, Magalang UJ, Brekken RA, Scherer PE. Mol Cell Biol. 2009 Aug;29(16):4467-83. doi: 10.1128/MCB.00192-09. Epub 2009 Jun 22. PMID: 19546236
In the news:
https://cancerworld.net/study-unveils-how-obesity-raises-cancer-risk/
https://www.tv2.no/nyheter/utenriks/forskere-kan-ha-funnet-nokkelen-til-et-lengre-liv/15812692/
Works
Search Professor Nils Henrik Halberg’s works on UQ eSpace
2024
Conference Publication
Interplay of the proteotoxic CEL-MODY protein and oncogenic Kras in pancreatic cancer development
Fjeld, Karianne, Alam, Jahedul, López, Diego Iglesias, Kuznetsova, Ksenia, Seierstad, Renate V., Verbeke, Caroline, Vaudel, Marc, Regel, Ivonne, Halberg, Nils and Molven, Anders (2024). Interplay of the proteotoxic CEL-MODY protein and oncogenic Kras in pancreatic cancer development. 56th European Pancreatic Club Meeting 2024, Santiago de Compostela, Spain, 26 - 29 June 2024. Amsterdam, Netherlands: Elsevier. doi: 10.1016/j.pan.2024.05.010
2024
Conference Publication
Detection of epigenetic priming in acinar cells after recovering from pancreatitis or metabolic stress
Wolff, Julia, Zhou, Quan, Schreiner, Nicole, Fahr, Lisa, Straub, Tobias, Mahajan, Ujjwal M., Holt, Eric, Bozdag, Beyza, Imhof, Axel, Mayerle, Julia, Halberg, Nils and Regel, Ivonne (2024). Detection of epigenetic priming in acinar cells after recovering from pancreatitis or metabolic stress. 56th European Pancreatic Club Meeting 2024, Santiago de Compostela, Spain, 26 - 29 June 2024. Amsterdam, Netherlands: Elsevier. doi: 10.1016/j.pan.2024.05.309
2024
Journal Article
PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels
Zhu, Qingzhang, Chen, Shiuhwei, Funcke, Jan-Bernd, Straub, Leon G., Lin, Qian, Zhao, Shangang, Joung, Chanmin, Zhang, Zhuzhen, Kim, Dae-Seok, Li, Na, Gliniak, Christy M., Lee, Charlotte, Cebrian-Serrano, Alberto, Pedersen, Line, Halberg, Nils, Gordillo, Ruth, Kusminski, Christine M. and Scherer, Philipp E. (2024). PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels. Nature Metabolism, 6 (7), 1347-1366. doi: 10.1038/s42255-024-01078-9
2023
Journal Article
Correction: The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer (Molecular Cancer, (2023), 22, 1, (86), 10.1186/s12943-023-01788-w)
Entrialgo‑Cadierno, Rodrigo, Cueto‑Ureña, Cristina, Welch, Connor, Feliu, Iker, Macaya, Irati, Vera, Laura, Morales, Xabier, Michelina, Sandra Vietti, Scaparone, Pietro, Lopez, Ines, Darbo, Elodie, Erice, Oihane, Vallejo, Adrian, Moreno, Haritz, Goñi‑Salaverri, Ainhoa, Lara‑Astiaso, David, Halberg, Nils, Cortes‑Dominguez, Ivan, Guruceaga, Elizabeth, Ambrogio, Chiara, Lecanda, Fernando and Vicent, Silve (2023). Correction: The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer (Molecular Cancer, (2023), 22, 1, (86), 10.1186/s12943-023-01788-w). Molecular Cancer, 22 (1) 97. doi: 10.1186/s12943-023-01795-x
2023
Journal Article
Limiting mitochondrial plasticity by targeting DRP1 induces metabolic reprogramming and reduces breast cancer brain metastases
Parida, Pravat Kumar, Marquez-Palencia, Mauricio, Ghosh, Suvranil, Khandelwal, Nitin, Kim, Kangsan, Nair, Vidhya, Liu, Xiao-Zheng, Vu, Hieu S., Zacharias, Lauren G., Gonzalez-Ericsson, Paula I., Sanders, Melinda E., Mobley, Bret C., McDonald, Jeffrey G., Lemoff, Andrew, Peng, Yan, Lewis, Cheryl, Vale, Gonçalo, Halberg, Nils, Arteaga, Carlos L., Hanker, Ariella B., DeBerardinis, Ralph J. and Malladi, Srinivas (2023). Limiting mitochondrial plasticity by targeting DRP1 induces metabolic reprogramming and reduces breast cancer brain metastases. Nature Cancer, 4 (6), 893-907. doi: 10.1038/s43018-023-00563-6
2022
Journal Article
C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer
Liu, Xiao-Zheng, Rulina, Anastasiia, Choi, Man Hung, Pedersen, Line, Lepland, Johanna, Takle, Sina T., Madeleine, Noelly, Peters, Stacey D’mello, Wogsland, Cara Ellen, Grøndal, Sturla Magnus, Lorens, James B., Goodarzi, Hani, Lønning, Per E., Knappskog, Stian, Molven, Anders and Halberg, Nils (2022). C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer. Nature Communications, 13 (1) 69, 69. doi: 10.1038/s41467-021-27734-2
2022
Journal Article
Carbon dot therapeutic platforms: administration, distribution, metabolism, excretion, toxicity, and therapeutic potential
Truskewycz, Adam, Yin, Hong, Halberg, Nils, Lai, Daniel T. H., Ball, Andrew S., Truong, Vi Khanh, Rybicka, Agata Marta and Cole, Ivan (2022). Carbon dot therapeutic platforms: administration, distribution, metabolism, excretion, toxicity, and therapeutic potential. Small, 18 (16) 2106342, 16. doi: 10.1002/smll.202106342
2021
Journal Article
High-dimensional immunotyping of tumors grown in obese and non-obese mice
Wogsland, Cara E., Lien, Hilde E., Pedersen, Line, Hanjra, Pahul, Grondal, Sturla M., Brekken, Rolf A., Lorens, James B. and Halberg, Nils (2021). High-dimensional immunotyping of tumors grown in obese and non-obese mice. DMM Disease Models and Mechanisms, 14 (4) dmm.048977, 1-18. doi: 10.1242/dmm.048977
2021
Journal Article
Cellular mechanisms linking cancers to obesity
Liu, Xiao-Zheng, Pedersen, Line and Halberg, Nils (2021). Cellular mechanisms linking cancers to obesity. Cell Stress, 5 (5), 55-72. doi: 10.15698/CST2021.05.248
2020
Journal Article
AXL Is a driver of stemness in normal mammary gland and breast cancer
Engelsen, Agnete S. T., Wnuk-Lipinska, Katarzyna, Bougnaud, Sebastien, Pelissier Vatter, Fanny A., Tiron, Crina, Villadsen, René, Miyano, Masaru, Lotsberg, Maria L., Madeleine, Noëlly, Panahandeh, Pouda, Dhakal, Sushil, Tan, Tuan Zea, Peters, Stacey D'mello, Grøndal, Sturla, Aziz, Sura M., Nord, Silje, Herfindal, Lars, Stampfer, Martha R., Sørlie, Therese, Brekken, Rolf A., Straume, Oddbjørn, Halberg, Nils, Gausdal, Gro, Thiery, Jean Paul, Akslen, Lars A., Petersen, Ole W., LaBarge, Mark A. and Lorens, James B. (2020). AXL Is a driver of stemness in normal mammary gland and breast cancer. iScience, 23 (11) 101649, 1-19. doi: 10.1016/j.isci.2020.101649
2020
Journal Article
Golgi-localized PAQR4 mediates antiapoptotic ceramidase activity in breast cancer
Pedersen, Line, Panahandeh, Pouda, Siraji, Muntequa I., Knappskog, Stian, Lønning, Per Eystein, Gordillo, Ruth, Scherer, Philipp E., Molven, Anders, Teigen, Knut and Halberg, Nils (2020). Golgi-localized PAQR4 mediates antiapoptotic ceramidase activity in breast cancer. Cancer Research, 80 (11), 2163-2174. doi: 10.1158/0008-5472.CAN-19-3177
2019
Journal Article
Upregulated PDK4 expression is a sensitive marker of increased fatty acid oxidation
Pettersen, Ina Katrine Nitschke, Tusubira, Deusdedit, Ashrafi, Hanan, Dyrstad, Sissel Elisabeth, Hansen, Lena, Liu, Xiao-Zheng, Nilsson, Linn Iren Hodneland, Løvsletten, Nils Gunnar, Berge, Kjetil, Wergedahl, Hege, Bjørndal, Bodil, Fluge, Øystein, Bruland, Ove, Rustan, Arild Christian, Halberg, Nils, Røsland, Gro Vatne, Berge, Rolf Kristian and Tronstad, Karl Johan (2019). Upregulated PDK4 expression is a sensitive marker of increased fatty acid oxidation. Mitochondrion, 49, 97-110. doi: 10.1016/j.mito.2019.07.009
2019
Journal Article
Human endotrophin as a driver of malignant tumor growth
Bu, Dawei, Crewe, Clair, Kusminski, Christine M., Gordillo, Ruth, Ghaben, Alexandra L., Kim, Min, Park, Jiyoung, Deng, Hui, Xiong, Wei, Liu, Xiao-Zheng, Lønning, Per Eystein, Halberg, Nils, Rios, Adan, Chang, Yujun, Gonzalez, Anneliese, Zhang, Ningyan, An, Zhiqiang and Scherer, Philipp E. (2019). Human endotrophin as a driver of malignant tumor growth. JCI Insight, 4 (9) e125094, 9. doi: 10.1172/jci.insight.125094
2017
Journal Article
Adipose HIF-1α causes obesity by suppressing brown adipose tissue thermogenesis
Jun, Jonathan C., Devera, Ronald, Unnikrishnan, Dileep, Shin, Mi-Kyung, Bevans-Fonti, Shannon, Yao, Qiaoling, Rathore, Aman, Younas, Haris, Halberg, Nils, Scherer, Philipp E. and Polotsky, Vsevolod Y. (2017). Adipose HIF-1α causes obesity by suppressing brown adipose tissue thermogenesis. Journal of Molecular Medicine, 95 (3), 287-297. doi: 10.1007/s00109-016-1480-6
2016
Journal Article
PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion
Halberg, Nils, Sengelaub, Caitlin A., Navrazhina, Kristina, Molina, Henrik, Uryu, Kunihiro and Tavazoie, Sohail F. (2016). PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion. Cancer Cell, 29 (3), 339-353. doi: 10.1016/j.ccell.2016.02.013
2016
Journal Article
PTPRN2 and PLCβ1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling
Sengelaub, Caitlin A., Navrazhina, Kristina, Ross, Jason B., Halberg, Nils and Tavazoie, Sohail F. (2016). PTPRN2 and PLCβ1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling. EMBO Journal, 35 (1), 62-76. doi: 10.15252/embj.201591973
2013
Journal Article
Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4
Drager, Luciano F., Yao, Qiaoling, Hernandez, Karen L., Shin, Mi-Kyung, Bevans-Fonti, Shannon, Gay, Jason, Sussan, Thomas E., Jun, Jonathan C., Myers, Allen C., Olivecrona, Gunilla, Schwartz, Alan R., Halberg, Nils, Scherer, Philipp E., Semenza, Gregg L., Powell, David R. and Polotsky, Vsevolod Y. (2013). Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4. American Journal of Respiratory and Critical Care Medicine, 188 (2), 240-248. doi: 10.1164/rccm.201209-1688OC
2013
Journal Article
Selective inhibition of Hypoxia-inducible factor 1α ameliorates adipose tissue dysfunction
Sun, Kai, Halberg, Nils, Khan, Mahmood, Magalang, Ulysses J. and Scherer, Philipp E. (2013). Selective inhibition of Hypoxia-inducible factor 1α ameliorates adipose tissue dysfunction. Molecular and Cellular Biology, 33 (5), 904-917. doi: 10.1128/MCB.00951-12
2012
Journal Article
MicroRNA regulation of cancer-endothelial interactions: Vesicular microRNAs on the move
Halberg, Nils, Alarcón, Claudio and Tavazoie, Sohail F. (2012). MicroRNA regulation of cancer-endothelial interactions: Vesicular microRNAs on the move. EMBO Journal, 31 (17), 3509-3510. doi: 10.1038/emboj.2012.198
2009
Journal Article
Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue
Halberg, Nils, Khan, Tayeba, Trujillo, Maria E., Wernstedt-Asterholm, Ingrid, Attie, Alan D., Sherwani, Shariq, Wang, Zhao V., Landskroner-Eiger, Shira, Dineen, Sean, Magalang, Ulysses J., Brekken, Rolf A. and Scherer, Philipp E. (2009). Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Molecular and Cellular Biology, 29 (16), 4467-4483. doi: 10.1128/MCB.00192-09
Supervision
Availability
- Dr Nils Henrik Halberg is:
- Available for supervision
Before you email them, read our advice on how to contact a supervisor.
Available projects
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What are the properties of cancer cells adapted to aberrant physiological environments?
Background
Obesity increases the risk of developing thirteen types of cancer that normal weight individuals may not develop despite of harbouring the same cancer risk loci. Globally, overweight/obesity may account for 544 300 cancer cases every year and is currently implicated in 15-20% of cancer-related mortalities. This places obesity second only to smoking as the most prevalent preventable cause of cancer. We have previously demonstrated that obesity is not associated with additional oncogenic genetic alterations that could explain the increased cancer risk. Instead, we demonstrate that cancer cells undergo adaptive epigenetic remodelling and gain tumour initiating properties when exposed to prolonged periods of obese conditions. This interaction between metabolic, epigenetic, and tumorigenic events currently represents significant knowledge gaps.
The aims are to:
• Uncover the relationship between systemic metabolic challenge as induced by physiological stressors and intracellular metabolite dynamics in cancer cells.
• Identification of the metabolites that are sufficient to drive tumour initiation – and how this is achieved.
• Determine how metabolite-driven epigenetic changes can display loci specificity.
• Discover the epigenetic, transcriptional and translational machinery required to that link physiological stressor to tumour initiation.
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How is the tumor ecosystem affected by obesity and how does that affect tumor outcomes?
Background:
Obesity increases the risk of developing thirteen types of cancer that normal weight individuals may not develop despite of harbouring the same cancer risk loci. Globally, overweight/obesity may account for 544 300 cancer cases every year and is currently implicated in 15-20% of cancer-related mortalities. This places obesity second only to smoking as the most prevalent preventable cause of cancer. We have previously demonstrated that obesity is not associated with additional oncogenic genetic alterations that could explain the increased cancer risk. Instead, we demonstrate that cancer cells undergo adaptive epigenetic remodelling and gain tumour initiating properties when exposed to prolonged periods of obese conditions. This interaction between metabolic, epigenetic, and tumorigenic events currently represents significant knowledge gaps.
The aims are to:
- Use spatial technologies to specify obesity dependent changes to the cancer ecosystem
- Develop appropriate mouse models of the cancer ecosystem in obese and non-obese condidtions.
Media
Enquiries
Contact Dr Nils Henrik Halberg directly for media enquiries about:
- Cancer
- Epigenetics
- Metabolism
- Metabolites
- obesity
- systems biology
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