ESR – estrogen signaling research group - Chunyan Zhao

The overall goal is the development of novel therapeutic strategies targeting estrogen signaling in metabolic disease, particularly 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. 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.

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. These studies revealed that hepatocyte-selective ERα ablation does not recapitulate the T2D phenotype. We are exploring several avenues to modulate estrogen signaling in breast cancer cells.

We have demonstrated that members of a family of E3 ubiquitin ligases can modulate ERα levels and cell proliferation and suggest that these proteins could constitute novel drug targets. 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 management of breast cancer.

Molecular mechanisms of estrogen signaling
The group is approaching the molecular mechanism of estrogen signaling in metabolic disease and breast cancer combining phenotypic and functional genomics data with the ultimate goal to identify novel diagnostic criteria and drug targets.

 

Group members

Deputy group leader for Karin Dahlman-Wright:

Senior researcher

Chunyan Zhao

Phone: +46-(0)8-524 811 26
Organizational unit: Dahlman-Wright
E-mail: Chunyan.Zhao@ki.se

Postdoc

Lucia Bialesová

Organizational unit: Department of Biosciences and Nutrition (BioNut), H2
E-mail: lucia.bialesova@ki.se

Pro-Vice-Chancellor

Karin Dahlman-Wright

E-mail: Karin.Dahlman-Wright@ki.se

Senior researcher

Hui Gao

Organizational unit: Dahlman-Wright
E-mail: Hui.Gao@ki.se

Lecturer senior

Lars-Arne Haldosen

Phone: +46-(0)8-524 811 60
Organizational unit: Dahlman-Wright
E-mail: Lars-arne.Haldosen@ki.se

Graduate Student

Huan He

Organizational unit: Dahlman-Wright
E-mail: huan.he@ki.se

Bioinformatician

Indranil Sinha

Phone: +46-(0)8-524 810 68
Organizational unit: Dahlman-Wright
E-mail: Indranil.Sinha.2@ki.se

HormonesMolecular endocrinology