PROFESSOR, HEAD OF DEPT
Name of group:Experimental Oncology
Additional position: PI, Dept. of Biosciences and Nutrition, Karolinska Institutet
Short description of research:
The research focuses on understanding key molecular mechanisms in cancer, using a combination of large-scale omic approaches, focused mechanistic experiments, andin vivo studies. The goal is to understand critical cancer pathways so that we can suggest better cancer treatments and preventive approaches and biomarkers to be tested and developed for clinical use.
The hormone estrogen can increase the risk of breast cancer, while simultaneously protect against colon cancer. It is not understood exactly how, but if we can achieve a detailed knowledge of this mechanism, we will be able to design approaches that can protect both men and women against colon cancer, without promoting breast cancer. Estrogenic signaling is mediated by the estrogen receptors, ERalpha and ERbeta. They are ligand-activated nuclear receptors and as such excellent therapeutic targets. Our research focuses on the estrogen-induced pathways in breast and colon cancer, sex differences, and the impact that exposure to environmental or dietary estrogenic compounds can have.
Related to this, is the identification of molecular mechanisms involving microRNAs and long non-coding RNAs. These molecules have great potential as novel biomarkers and therapeutic targets. They appear to have key roles in the metastatic capacity of cancer cells and are, to various extents, regulated by the estrogen receptors. The roles of non-coding RNA in this respect are central to reveal, as a cancer cell’s capacity to set metastasis is the ominous ability that can determine the prognosis of this disease.
During the COVID-19 pandemic we were also involved in surveilling the outbreak through qPCR analysis of wastewater.
How estrogen receptors of the colon create a microenvironment that suppress carcinogenesis - for cancer prevention and treatment (funded by VR Swedish Research Council, Medicine and Health, PI: Williams)
Prevention of colorectal cancer through estrogen receptor beta activation (funded by Cancerfonden, PI: Williams)
Precision pathology - prediction of patient specific drug response (funded by Region Stockholm HMT, PI: Hartman)
QuantumSense - Tunnelströmsdetektion av biomolekyler för snabb avkodning av DNA och RNA (funded by VR Swedish Research Council, forskningsmiljö, PI: Stemme)
High-fat diet and estrogen modulate the gut microbiota in a sex-dependent manner in mice. Hases L, Stepanauskaite L, Birgersson M, Brusselaers N, Schuppe-Koistinen I, Archer A, Engstrand L, Williams C. Communications Biology (2023)
Long-term SARS-CoV-2 surveillance in the wastewater of Stockholm: What lessons can be learned from the Swedish perspective? Perez-Zabaleta M, Archer A, Khatami K, Jafferali MH, Nandy P, Atasoy M, Birgersson M, Williams C, Cetecioglu Z. Sci Total Environ (2023) PMID: 36356735
Colitis Induces Sex-Specific Intestinal Transcriptomic Responses in Mice. Hases L, Birgersson M, Indukuri R, Archer A, Williams C. Int J Mol Sci. (2022) PMID: 36142324
Nuclear receptors: from molecular mechanisms to therapeutics.Frigo DE, Bondesson M, Williams C. Essays Biochem (2021) PMID: 34825698 (review)
Genome-wide estrogen receptor β chromatin binding in human colon cancer cells reveals its tumor suppressor activity.Indukuri R, Jafferali MH, Song D, Damdimopoulos A, Hases L, Zhao C, Archer A, Williams C. Int J Cancer (2021) PMID: 33754337.
Blocking Fra-1 sensitizes triple-negative breast cancer to PARP inhibitor. Song D, He H, Sinha I, Hases L, Yan F, Archer A, Haldosen LA, Zhao C, Williams C. Cancer Lett (2021) PMID: 33652085.
Menopausal hormone therapies and risk of colorectal cancer: a Swedish matched-cohort study. Liu Q, Simin J, Debelius J, Fall K, Sadr-Azodi O, Engstrand L, Williams C, Brusselaers N. Aliment Pharmacol Ther. 2021 PMID: 33857339.
Intestinal estrogen receptor beta suppresses colon inflammation and tumorigenesis in both sexes. Hases L, Indukuri R, Birgersson M, Nguyen-Vu T, Lozano R, Saxena A, Hartman J, Frasor J, Gustafsson JÅ, Katajisto P, Archer A, Williams C. Cancer Lett(2020) PMID: 32711097.
A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. Berger AC, Korkut A, Kanchi RS, Hegde AM, Lenoir W, Liu W, Liu Y, Fan H, Shen H, Ravikumar V, Rao A, Schultz A, Li X, Sumazin P, Williams C, Mestdagh P, Gunaratne PH, Yau C, Bowlby R, Robertson AG, Tiezzi DG, Wang C, Cherniack AD, Godwin AK, Kuderer NM, Rader JS, Zuna RE, Sood AK, Lazar AJ, Ojesina AI, Adebamowo C, Adebamowo SN, Baggerly KA, Chen TW, Chiu HS, Lefever S, Liu L, MacKenzie K, Orsulic S, Roszik J, Shelley CS, Song Q, Vellano CP, Wentzensen N; Cancer Genome Atlas Research Network, Weinstein JN, Mills GB, Levine DA, Akbani R. Cancer Cell (2018) PMID: 29622464
Insufficient antibody validation challenges oestrogen receptor beta research.Andersson S, Sundberg M, Pristovsek N, Ibrahim A, Jonsson P, Katona B, Clausson CM, Zieba A, Ramström M, Söderberg O, Williams C, Asplund A. Nature Communications (2017) PMID: 28643774
miR-206 inhibits cell migration through direct targeting of the actin-binding protein coronin 1C in triple-negative breast cancer. Wang J, Tsouko E, Jonsson P, Bergh J, Hartman J, Aydogdu E, Williams C. Molecular Oncology (2014) PMID: 25074552