Manuela Tumiati's dissertation generated a novel breast cancer mouse model with potential to explore therapeutic approaches

Breast cancer is the most common cancer among women. Many of the known breast cancer susceptibility genes, such as BRCA1, are involved in repair of DNA double-strand breaks. The main aim of M.Sc. Manuela Tumiati’s thesis, to be publicly examined today, 8 September, was to characterize and understand the mechanisms by which defects in another DNA repair gene, RAD51C, predispose women to breast and ovarian cancer. Manuela will defend her doctoral dissertation entitled "Rad51c is a tumor suppressor in mammary and sebaceous glands" in the Faculty of Biological and Environmental Sciences.

Manuela Tumiati graduated from the University of Milan, Italy, in 2007 having Medical Biotechnology as her major subject. She was interested in finding a PhD position abroad, applied for a FIMM-EMBL PhD student position and was selected to the program among the first students in 2009. She has done her thesis work in the group led by FIMM-EMBL Group Leader Sergey Kuznetsov who was also her supervisor.

An essential part of her thesis project was to generate a conditional knock-out mouse model that would enable studying the Rad51c gene. Based on earlier work the group already knew that mice lacking this gene die during early embryogenesis and that mice having mutations in both Rad51c  and a well-known tumour suppressor gene Trp53 develop multiple tumors.

Manuela’s thesis consists of two publications and one manuscript currently being under review. In the first part of her study she concluded that loss of Rad51c alone is not sufficient to trigger tumorigenesis but inactivation of Trp53 is also needed. Next, she was able to show a remarkably close resemblance between mouse and human mammary carcinomas. In the last part of her thesis work Manuela concentrated on the mechanisms by which Rad51c causes malignant transformation. She described signs of genomic instability in several mouse and human cell lines and thus proved that Rad51c is indeed a tumor suppressor.

Picture: The Elephant (Mouse Meibomian Gland) by Manuela Tumiati

“The fact that the mouse tumors possess the same features as human tumors opens the door for experimenting with targeted therapies that could prove beneficial in the treatment of human breast cancers”, Manuela explains.  “In addition, the mouse tumors are detectable very early, creating an opportunity to develop early diagnostic and treatment tools.”

“My thesis project has largely been a one-woman show. When working with living organisms such as mice you have to patient and overcome the inevitable adversity. Generating the mouse model took many years but luckily it turned out to be exactly what we needed and thus well worth the time spent.”

Outside the work Manuela relaxes with her favorite hobbies, kick-boxing and crafting. She has already started her post-doctoral research project in the group of Liisa Kauppi, which belongs to the Genome-Scale Biology research program of the Faculty of Medicine.

Manuela has enjoyed working at FIMM and she especially values the interactive and international atmosphere of the institute.

“Being one of the first PhD students at FIMM meant that we didn’t have many people to ask for advice or proper laboratory infrastructure available when we started. The thesis work has been a constructive journey for me, but I would definitely do it again!”

The public examination of Manueala Tumiati’s thesis will take place on 8 September 2015 at 12:00 in the lecture hall 3 of Biomedicum Helsinki 1, Haartmaninkatu 8. Associate professor Madalena Tarsounas, University of Oxford 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.