Cecilia Williams

Name of group:Experimental Oncology at SciLifelab

Additional position: Dept. of Medicine Huddinge, Karolinska Institutet (20%)

Short description of research:
The hormone estrogen can increase the risk of breast cancer while simultaneously protecting 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 ligand-activated estrogen receptors ERalpha, ERbeta, and GPER1 which are excellent therapeutic targets. Our research focuses on understanding key molecular mechanisms in cancer, including the impact of sex differences, a high-fat diet, immune cells, and the microbiome, using a combination of large-scale omic approaches, focused mechanistic experiments, and in 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. Our research also focuses on the estrogen-regulated molecular mechanisms impacting ovarian cancer and fertility.

Research projects:
How estrogen receptors of the colon create a microenvironment that suppresses carcinogenesis - for cancer prevention and treatment (funded by VR Swedish Research Council, Medicine and Health, PI: Williams)

How estrogens modify the colon tumor microenvironment – implications for prevention and therapy (funded by Cancerfonden, PI: Williams)

Exploring markers of the tumor microenvironment to predict response to immune checkpoint inhibitors in colorectal cancer (funded by Region Stockholm HMT, PI: Williams, co-PI Martling)

Selected publications:

Spatial profiling of the mouse colonic immune landscape associated with colitis and sex. Holm M, Stepanauskaitė L, Bäckström A, Birgersson M, Socciarelli F, Archer A, Stadler C, Williams C.Commun Biol. (2024) 7(1):1595. doi: 10.1038/s42003-024-07276-1

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.Commun Biol. (2023)

Ovarian ERβ cistrome and transcriptome reveal chromatin interaction with LRH-1. Birgersson M, Indukuri R, Lindquist L, Stepanauskaite L, Luo Q, Deng Q, Archer A, Williams C. BMC Biol. (2023) 21(1):277. doi: 10.1186/s12915-023-01773-1.

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