KTH Royal Institute of Technology (Professor), Karolinska Institutet (Visiting Professor), University of Houston (adjunct faculty)
The Williams group focuses on understanding key molecular mechanisms in cancer, using a combination of omic approaches, focused mechanistic experiments, and in vivo studies. The goal is to understand pathways critical in cancer progression so that we can define biomarkers of their activity and suggest better cancer treatments and approaches.
Estrogen signaling and cancer
One main focus is to understand the impact of the estrogenic pathway in cancer development. The hormone estrogen drives breast cancer, while it simultaneously protects against colon cancer. If we can achieve a detailed knowledge of this mechanism, we would be able to design approaches that can protect against colon cancer while not promoting breast cancer. Estrogenic signaling is mediated by the nuclear estrogen receptors ERalpha and ERbeta, and by the transmembrane G-coupled estrogen receptor GPER1. Inactivation of ERalpha is currently one of the most successful breast cancer treatments. However, resistance frequently develops and in order to overcome this, we need to understand the detailed mechanisms. Our research also helps understand the impact that environmental or dietary estrogenic exposure may have.
Non-coding RNAs in cancer
Related to this, is the identification of molecular mechanisms involving microRNAs and long non-coding RNAs. The roles of these molecules are not fully understood, but there are indications that they have great potential as novel biomarkers and therapeutic targets. Non-coding RNA molecules are, to various extents, regulated by the estrogen receptors and are likely to contribute to the estrogenic effects. They appear to have key roles in the metastatic capacity of cancer cells, and possible influence so called cancer stem cells. The roles of non-coding RNA in this respect are central to reveal, as the cancer’s capacity to set metastasis is the ominous ability that can determine the prognosis for the patient.
- Utilizing large-scale omic techniques to decipher nuclear receptor and non-coding RNA mechanisms in cancer (VINNOVA and EU, PI: Williams)
- Elucidating the mechanism of estrogen receptor beta in colon carcinogenesis (US National Institutes of Health NIH via NCI, PI: Williams)
- Integrating organotypic models and omics approaches for translation of emerging colorectal cancer therapies and biomarkers (Stockholm County Council, HMT, PI:Williams)
- Understanding estrogen’s protective role against colorectal cancer development (Cancerfonden, PI:Williams)
Cecilia Williams, Group leader
Amena Archer, Lab manager
Ahmed Ibrahim, Post doc
Fahmi Mesmar, PhD student
Linnea Pettersson, PhD student
Rajitha Indukuri, PhD student
(Comprehensive list at goo.gl/d45SKx)
Insufficient antibody validation challenges estrogen receptor beta research
Andersson S, Sundberg M, Pristovsek N, Ibrahim A, Jonsson P, Katona B, Clausson C-M, Zieba A, Ramström M, Söderberg O, Williams C#, Asplund A.
Nature Communications (2017) 8:15840 PMID: 28643774
Estrogen receptor beta reduces colon cancer metastasis through a novel miR-205 – PROX1 mechanism
Nguyen-Vu T, Wang J, Mesmar F, Mukhopadhyay S, Saxena A, McCollum CW, Gustafsson JÅ, Bondesson M, Williams C#.
Oncotarget (2016) 5;7:42159-42171 PMID: 27283988
Single-molecule sequencing reveals estrogen-regulated clinically relevant lncRNAs in breast cancer
Jonsson P, Coarfa C, Mesmar F, Raz T, Rajapakshe K, Thompson JF, Gunaratne PH, Williams C#.
Molecular Endocrinology (2015) 29:1634-45 PMID: 26426411
miR-200a inhibits migration of triple-negative breast cancer cells through direct repression of the EPHA2 oncogene
Tsouko E, Wang J, Frigo DE, Aydoğdu E, Williams C#.
Carcinogenesis (2015) 36:1051-60 PMID: 26088362
Insights into the invasiveness of triple-negative breast cancer from genome-wide profiling of transcription factor AP-1
Zhao C#, Qiao Y, Jonsson P, Wang J, Xu L, Rouhi P, Sinha I, Kharman-Biz A, Cao A, Williams C, Dahlman-Wright K.
Cancer Research (2014) 74:3983-94 PMID: 24830720.
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