Santo Spencer Briguglio is a Biochemistry and Biotechnology student at the University of Windsor. With his 2013-2014 research studentship, he worked with Dr. Lisa Porter at the Windsor Cancer Research Group on a project focused on medulloblastoma research.

Santo’s project was funded in memory of Erin Michelle Leis.

About the Research

Project: “The Efficacy of Cdk Inhibitors as a Novel Therapeutic Approach for Medulloblastoma”

Project Description

Medulloblastoma is the most prevalent of all childhood brain cancers, with average five-year survival rates of approximately 62%. Recent work has determined that there are at least four very distinct types of this disease that have different prognoses and require independent treatment strategies.

Among these groups, those denoted as “Group C” have the worst probability of survival, seeing little benefit from the current aggressive chemotherapy/radiotherapy approach. It is of high priority to find novel therapeutic strategies for this subset of patients.

We, and others, have generated data to support that targeting a specific group of proteins known as Cdks represents an important therapeutic avenue that may offer exceptional benefits to “Group C” medulloblastoma patients. This project will optimize how these proteins will be best targeted in medulloblastoma and will begin to test these ideas using clinically available Cdk inhibitors. This project holds promise for improving survival and quality of life for a subset of medulloblastoma patients that currently rely on suboptimal treatment options.

Over the course of two summer terms, Spencer will be trained to conduct experiments and analysis using the Windsor Cancer Research Group’s unique zebrafish model. This model closely resembles the way brain tumour samples respond in the human body. Spencer will monitor specific aspects of human brain tumour growth, the ability to move to new sites and the response to many combinations of drugs. He will use this model to determine the expression and regulation of a unique class of proteins referred to as ‘cyclin-like proteins’ that our lab has found to drive drug resistance and relapse in a number of human brain cancers.

This information will then used to predict and test whether specific cases of medulloblastoma will respond more favourably to Cdk inhibitors. He will also manipulate the levels of the ‘cyclin-like proteins’ toward the goal of making resistant medulloblastoma cases sensitive to the Cdk inhibitor treatment.

About Santo, in his own words…

Being awarded a Brain Tumour Research Studentship means that I can pursue not only my career in research, but my dreams and ideas as well. The donations supporting this scholarship will be invaluable in my continued training in cancer cell biology.

Ultimately I aim to make significant advances in our understanding of how brain tumours form and progress. This studentship has opened a door for me; I am grateful that I am able to pursue a career that I love and am passionate about. Sincere thanks to Brain Tumour Foundation of Canada and all the donors that have supported these important awards. I am motivated to make the most of this opportunity and to truly make an impact on our society.

My interest in brain tumour research ultimately stems from my passion for science. Whether is it molecular biology, nanotechnology, quantum mechanics or astrophysics; science never ceases to amaze me. Working in a lab is always something I’ve wanted to do since watching Bill Nye The Science Guy as a child. I also want to make a difference in the world and what better way to do so than to research cancer?

I am so excited to be working in the lab for two summers, this is something I would pay to do. Just the fact that I can help advance an area in science or help to understand how cancer works is mind-boggling for me; Science rules!

Final Report

When we first began the project not much was known about how certain drugs, specifically CDK-inhibitors, affect the many processes involved in cell cycle regulation and tumour suppression. Our aim is to study the effects of CDK-inhibitors on brain tumour cells in vitro and in vivo. Part of doing this is to develop an animal model to study the effect of these drugs on a large scale with various cell lines and drugs. The summer of 2014 was largely spent observing cells in vitro and the changes caused specifically when a gene called SPDYA, which encodes the Spy1 protein, was overexpressed. Spy1 has been shown to be overly abundant in many malignant tumours and is currently being investigated by our lab to further elucidate exactly what it is doing in the cells. Since beginning my research studentship with Dr. Porter (under the supervision of her graduate student Janice Tubman) we have nearly completely optimized and developed an in vivo zebrafish model for the large scale testing of drugs on tumour metastasis. The benefits of this model is that it is cheap, relatively easy to perform, time-efficient and provides the accuracy commonly associated with in vivo models. The simplicity of the model also leaves it open to making a partially automated system to more easily control environmental conditions, dosage, data acquisition, etc.

This research can improve the treatment that brain tumour patients receive by allowing novel therapeutic approaches to be investigated on a patient tumour cells in the animal model. This will allow for more accurate assessment of the efficacy of the treatment received by the patient. In the future, more data collection from various cell lines and drug trials will help to further optimize and refine the model. CDK-inhibitory drugs show much promise in the area of chemotherapeutics specifically for cancers but can also be investigated for other non-cancerous tumour causing illnesses. Further investigation into how CDK-inhibitory drugs affect the Spy1 protein in multiple cell lines is therefore the next upcoming goal in research. Of course, these goals and others (with some adjustment to the protocol) can be realized much more easily with the use of our zebrafish model.

Read more from Spencer’s final report

About my experience

It is with great appreciation that I am sending this final report to conclude my 2013-15 research studentship generously provided to me by your organization and its donors. Of course, the end to a good experience is never easily met but the invaluable knowledge and experience I have gained from this has positively influenced my own life and I hope will one day help others. I would like to thank the Brain Tumour Foundation of Canada, its donors and its supporting members, for the opportunity granted to me.

After these two years of research, I have greatly expanded my knowledge and understanding of various scientific and personal matters. From this studentship, I have renewed aspirations of continuing on in a scientific setting and many doors are now open to me that were not open before. I plan on continuing my research in the future with a different approach. I realized that my strengths and interest lie greatly in physical chemistry as well as biochemistry and I am hoping to use these to my full ability to continue researching cancer. In conclusion, receiving this award showed me the best way for me to change more lives and help people as well as put me on a path to achieve my goals; something a lot of people my age don’t get to experience.