Research interests

The overall goal is the development of novel therapeutic strategies in type 2 diabetes (T2D) and breast cancer.

There is substantial evidence for the involvement of estrogen signaling and estrogen receptors (ERs) in T2D combined with a great unmet medical need for this disease. ERα knock-out (KO) mice are obese and display insulin resistance; however, the target tissues responsible for these effects remain elusive. Tissue-selective KO animals are well posed to address this issue and we have generated mice with ERα KO in hepatocytes, adipocytes and pancreatic β-cells and are correlating observed phenotypes with molecular details such as changes in gene expression profiles.

Estrogen signaling promotes breast cancer growth and ER antagonists represent first line therapy for ER positive breast cancer. However, all tumors do not respond to this therapy and additionally many tumors eventually acquire ER antagonist resistance supporting a need to develop novel therapeutic strategies. We are exploring several avenues to modulate estrogen signaling in breast cancer cells. The extensive cross talk between estrogen signaling and AP-1 signaling that we have described indicates a potential of modulators of AP-1 family in the management of ER positive breast cancer.

Triple negative breast cancer (TNBC), that do not express ERs, represent some of the most aggressive forms of breast cancer. We have shown that the AP-1 transcription factor component Fra-1 is overexpressed in basal-like breast tumors, and that its expression level has high prognostic significance. Depletion of Fra-1 or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro and reduces cellular invasion in vivo. Exploring the AP-1 cistrome and the AP-1-regulated transcriptome, we provide insights into the transcriptional regulatory networks of AP-1 in TNBC cells, identifying direct targets of the Fra-1/c-Jun heterodimer involved in cell proliferation, cell adhesion, and cell-cell contact.

Group members

Hui Gao, Research assistant
Lucia Bialešová, Post doc
Lars-Arne Haldosén, Lecturer
Min Jia, Post doc
Amirhossein Kharman Biz, PhD-student
Yichun Qiao, PhD-student
Indranil Sinha, Post doc
Chunyan Zhao, Researcher
Jian Zhu, PhD-student

Contact

karin.dahlman-wright@scilifelab.se