Shows researchers at Biodesign Europe Event

BioDesign Europe supports trans-atlantic collaboration through project targeting breast cancer gene

Triple negative breast cancer (TNBC) accounts for approximately 10% of all breast cancers and is associated with a more aggressive disease. The gene TP53 is a master regulator of the cell, and the protein form of TP53, p53 plays a critical role in repairing damage to our DNA which can prevent cancer.

When cancer occurs, changes in that cancer's DNA (mutations) can make it harder to treat. TP53 is the most mutated gene in cancer, and interestingly 80% of TNBCs have TP53 mutations. Understanding the role of TP53 mutations can inform both scientists and patients as to the aggressiveness of their cancer. The goal of research into TP53 mutations is to develop more effective treatments for these cancers.

The outcome of the transatlantic collaboration between researchers at Dublin City University and Arizona State University is to uncover how different p53 mutations result in resistance to chemotherapy. 

In Jin Park and Josh LaBaer’s lab in ASU, they have been working on TP53 mutations in breast cancer, and have demonstrated that some TP53 mutations can cause treatment resistance, while others make the disease spread faster. 

Dr Alex Eustace’s lab has extensive experience in the preclinical assessment of novel treatment strategies for hard-to-treat cancers.  Research from the Eustace lab has led to the initiation of several early phase clinical trials in women with breast cancer.  

Dr Mehdi Nikkhah from ASU has developed a laboratory based 3D-microfluidic device which aims to model the environment in which a tumour exists in the body.  This lab on chip technology has been around since 2015, but the study of p53 mutations in cell invasion, and drug treatment are novel uses.  The benefits of these 3D-microfluidic devices are that they reflect cancer growth and response to treatment more effectively than testing cells on a petri dish.

Lydia’s research at DCU aims to integrate the goals of the 3 labs by identifying the optimal chemotherapy drug concentrations for treating TP53 mutant cells in the 3D-microfluidic devices.  Whilst measurement of drug response is easily achieved in petri-dishes, it is far more complicated in the 3D-microfluidic devices.  Lydia’s role in DCU is to optimise these drug treatments, to enable her to further study the TP53 mutations when she returns to ASU.

This project has brought ASU PhD student Lydia Sakala to Dublin to collaborate with Dr Alex Eustace.  This follows a reciprocal arrangement where DCU PhD student Grace Colley worked in Dr Jin Park’s lab in ASU. Grace was the first PhD student to participate in the exciting BioDesign Europe student exchange program.

Lydia and Grace spent time working in the same lab in ASU, and now Lydia is spending the semester in DCU working on the next phase of this ambitious research project. Lydia and Grace worked with the same TP53 mutations in Jin Park’s lab during Grace’s visit. Lydia will continue her work with these TP53 mutations whilst at DCU.

Lydia Sakala said

“I was excited to work with Dr. Alex Eustace, given his expertise in designing cancer drug treatment experiments. While I've worked with p53 mutations in our microfluidic device for a few years, I hadn't tested anticancer drugs in it before. Dr. Eustace has been incredibly helpful in guiding me on designing experiments to determine the optimal drug concentrations and testing their effects on p53 mutations within the device.”

Dr Alex Eustace said

“We were intrigued by the work generated by the LaBaer, Park and Nikkhah labs.  Lydia’s research strongly aligns with the goals of my research team.  We believe this burgeoning  collaboration, and the work on this project will lead to more opportunities for scientific exploration.”

Biodesign Europe, led by Executive Director, Prof Nicholas Dunne, combines the expertise and infrastructure of ASU’s renowned Biodesign Institute with DCU’s cutting-edge research capabilities, fostering a transdisciplinary approach to solving complex global problems. Biodesign Europe develops initiatives such as the ASU-DCU Collaborative PhD programme which funds PhD students to work on collaborative projects that address urgent global challenges such as healthcare technology and sustainability and also provides a transdisciplinary and international research experience for PhD students.