Yuexi Gu's dissertation unveils new features of the breast cancer type 1 susceptibility protein

Breast cancer is the most common type of cancer among women worldwide, and accounts for the second highest cause of cancer related deaths. Ten percentage of breast cancer cases are caused by mutations in known breast cancer susceptibility genes such as BRCA1. Women having a mutation within this gene have up to 80% chance of developing breast cancer in their lifetime.

The main aim of M.Sc. Yuexi Gu’s thesis, to be publically examined tomorrow, 16 June, was to better understand the biological nature of BRCA1-mutant breast cancers in order to develop potential therapeutics for their treatment.

Yuexi Gu has done his thesis work at FIMM in the group led by FIMM-EMBL Group Leader Sergey Kuznetsov who was also his supervisor. Yuexi will defend his doctoral dissertation entitled "Implications of BRCA1 mutations in basal-like breast cancer development and treatment" in the Faculty of Biological and Environmental Sciences.

Yuexi Gu graduated from the National Center of Biomedical Analysis (NCBA) in Beijing in 2009 having cell biology as his major subject. He noticed the FIMM-EMBL PhD student call announcement in Naturejobs.com and got interested both about the program and the possibility to explore a completely different country and culture. He was selected to the program later in 2009.

Yuexi’s thesis consists of two publications and one manuscript. In the first part of the study, the group collected and characterized four breast cancer cell lines bearing different BRCA1 mutations.  They also carried out a high-throughput-screen on BRCA1-mutant and wild-type cell lines. The cell lines studied were shown to have different properties and also vary in terms of drug sensitivity.

Next, to minimize genetic heterogeneity between the cell lines, the group utilized siRNA-mediated gene silencing of the BRCA1 gene. After performing another high-throughput chemical compound screen they were able to show that two proteasome inhibitors selectively killed the BRCA1-depleted cells.

“This result is especially interesting, since one of the proteasome inhibitors that we found as a hit from our screening, Bortezomib, has already been approved for the treatment of multiple myeloma, which demonstrates its safety in clinical use. Our findings raise the possibility that this drug could be used for the treatment of BRCA1-associated cancers,” Yuexi explains.

“Our findings that extended the functions of BRCA1 from DNA damage response and repair to unfolded protein response and cell cycle regulation were also quite exciting. Our data suggest that BRCA1 has DNA repair-independent functions that may potentially be used to target BRCA1-deficient cancer cells.”

Yuexi has enjoyed working at FIMM, and has especially appreciated the collaborative and generally relaxed atmosphere of the institute. In the future, Yuexi will continue his scientific career but will return back to the East to be closer to his family.

“I would like to thank my supervisor and my thesis committee members, Professor Marikki Laiho and Dr. Juha Klefström, for the scientific knowledge that I learned from them. Furthermore, I would like to thank my colleagues, and everyone from FIMM, for their kind help to me, as well as a lot of fun that we’ve had together in the past five years," Yuexi continues.

The public examination of Yuexi Gu’s thesis will take place on 16 June 2015 at 12:00 in the lecture hall 2 of Biomedicum Helsinki 1, Haartmaninkatu 8. Associate professor Claus Storgaard Sørensen, University of Copenhagen will serve as the opponent, and Professor Minna Nyström as the custos.

The dissertation is also available in electronic form and can be downloaded here.