UNDERGRADS 2025 – Porter Lab

Christopher Jaworski

Glioblastoma (GBM) stands as one of the most lethal and aggressive brain cancers, often defying current treatment strategies. The outlook for patients remains grim, with average survival hovering around just 14 months after diagnosis. A major reason for this is the tumor’s ability to resist therapy and recur, often driven by a complex network of cellular interactions within the tumor microenvironment. My research focuses on understanding the relationship between glioblastoma and a group of cells known as cancer-associated fibroblasts (CAFs). CAFs play a critical role in shaping the tumor environment by promoting tumor growth, supporting resistance to therapies, and enhancing invasive behavior. A protein of particular interest in our studies is YKL-40—a glycoprotein that is highly expressed in the mesenchymal subtype of GBM. This subtype is known for its aggressive nature and poor response to conventional treatments. By investigating how CAFs and tumor-initiating cells communicate through YKL-40, we aim to identify vulnerabilities that could lead to more effective treatment strategies. We’re also working with brain tumor organoids to model these interactions more realistically, and using techniques like shRNA knockdowns to probe the role of YKL-40 more precisely.

My journey in research began in my second year of university when I joined the Porter Lab. I entered as a volunteer, initially gaining exposure to the fundamentals of cancer biology. Through the Peer Mentor Network, I was mentored by upper-year students who helped me develop a foundational understanding of lab techniques and experimental design. As I grew more confident and capable, I began contributing more directly to ongoing experiments and even helped identify gaps in existing research that informed new directions for study. By the time I reached my upper years, I had the privilege of having my own project, from hypothesis formation to troubleshooting complex protocols. This experience has sharpened my analytical thinking and strengthened my collaborative skills, especially through interdisciplinary discussions with researchers across different fields. Being part of such a dynamic lab has deepened my appreciation for the intricacies of cancer research and sparked a commitment to lifelong learning and scientific inquiry. I’m incredibly thankful to Dr. Porter and the entire lab team for their mentorship, support, and trust in my development. This journey has not only shaped my academic path but also inspired me to continue contributing to the broader fight against cancer.

Glioblastoma (GBM) is the most aggressive type of brain tumour, characterized by its highly infiltrative and heterogeneous nature, which poses significant challenges to standard therapies. The presence of therapy-resistant Glioma Stem Cells (GSCs) contributes to GBM heterogeneity. Cancer cells (including GBM) are characterized by uncontrolled cell proliferation, which is linked to cell cycle dysregulation. SPY1 (SPDYA/RingoA) is an atypical cell cycle regulator that overrides cell cycle checkpoints, aiding in uncontrolled cell proliferation and survival through unique activation of CDKs. In GBM, elevated levels of SPY1 regulate CDK2 activity and drive clonal expansion of CD133+ GSCs. SPY1-CDK2 can also activate RNA-binding protein, Musashi-1 (MSI1), which plays a critical role in GSC maintenance through post-transcriptional regulation of NUMB and Notch pathway. MSI1 supports GSC populations to drive tumor

initiation and resistance to differentiation. This study aims to understand the role of MSI1 in maintaining GSC properties and its potential correlation with specific subgroups, and how MSI1 influences GSC self-renewal, proliferation, and response to therapies, with the goal of identifying novel therapeutic strategies to overcome treatment resistance in GBM. To demonstrate this, established GBM cell lines were infected with short hairpin (sh) MSI1 lentivirus, which resulted in reduced proliferation and self-renewal. The Zebrafish PDX platform was used to further validate the effects, confirming the impact of the MSI1 knockdown

Being part of the Porter Lab family was one of the most amazing and rewarding experiences of my undergraduate studies. It offered far more than experimental training – it provided a supportive, intellectually stimulating environment where I learned to think critically, troubleshoot experiments, and develop my intrapersonal skills, which will help me in the real world. From the beginning, I was welcomed into a community that values both scientific excellence and personal growth. Whether it was executing the experiment, analyzing data, or collaborating with your lab peers, every task contributed to my development as a researcher. The most important thing I’ve learned during the whole experience is the value of perseverance. You are bound to experimental errors that may alter your results, but you have to see these setbacks as opportunities to rethink and improve, not as failures.

Glioblastoma (GBM) is the most lethal and aggressive primary brain tumour affecting the central nervous system. Despite standard treatments, prognosis remains poor due to several barriers that limit successful treatment such as the presence of the blood-brain barrier, tumour heterogeneity, and glioma stem cells (GSCs). GSCs are known to increase aggressiveness and hinder therapy response. A notable GSC marker is the CD44 receptor, which is activated by its primary ligand, hyaluronic acid (HA), to promote cancer progression. High CD44 expression in GBM is correlated to increased aggressiveness, stemness, proliferation and, ultimately, poorer prognosis. Nanoparticle therapies are an emerging field of cancer research that allow for selective targeting of GSC populations. Our lab has shown that HA-Conjugated Nanoparticles (HA-CPNs) can selectively target CD44+ cells, eliciting anti-tumour effects both in vitro and in vivo. Within my project, I utilize HA-CPNs to target GSC populations within a biologically relevant model known as glioblastoma organoids. Organoids mimic real 3D tumour tissues making them a suitable model to study the effects of HA-CPNs on GSC regulation.

My journey within Porter Lab, starting in my second year of undergraduate studies, has provided me with some of the most rewarding experiences of my entire undergraduate career. I have been extremely fortunate to work alongside a team of talented students and RAs that I view as incredible role models and mentors. My time in lab has expanded my ability to problem solve, think critically, and above all has made me a more resilient person, appreciative of the intricacies of scientific discovery. I am extremely grateful for all of the opportunities, support, and guidance I have received from Dr. Porter, Dr. Lubanska, and the whole Porter Lab team this past year!

My project focuses on determining the potential of the CDK1/2 inhibitor Dinaciclib as a therapeutic direction for prostate cancer (PC). Adenocarcinoma prostate cancer (AdPC) represents 95% of all PC cases and has several treatment options available, such as surgery, chemotherapy, and hormone therapy, like androgen deprivation therapy (ADT). ADT works by blocking the production of androgens in the body, such as testosterone, to reduce the proliferation of prostate cancer cells. However, some patients do become resistant to ADT, leading to treatment-resistant populations of PC to emerge, called castration-resistant prostate cancer (CRPC). CRPC has a median-survival rate of 1-2 years and is much more aggressive than AdPC. A common treatment method used for CRPC is AR inhibitors, which block the activity of the androgen receptor (AR) outright to slow the proliferation of the prostate cancer cells. However, patients can also become resistant to this form of therapy, and differentiate into a treatment-resistant form called neuroendocrine prostate cancer (NEPC). NEPC is the most aggressive and deadly subtype of prostate cancer, and has a 7-month median survival rate. Furthermore, the downregulation of prostate-specific membrane antigen (PSMA), an important detection target, and AR in the transdifferentiation to NEPC further contribute to the poor prognosis of this type of cancer. Our lab proposes targeting the cell cycle to slow the proliferation of prostate cancer, using a CDK1/2 inhibitor named Dinaciclib. My project uses three prostate cancer cell lines to test the efficacy of Dinaciclib in vitro in stopping the proliferation of prostate cancer cells: LNCaP-FBS, an AdPC cell line, LNCaP-CSS, a CRPC cell line, and NCI-H660, an NEPC cell line. My project also uses zebrafish as an in vivo model to test Dinaciclib’s effect on tumour burden, where zebrafish have been injected with prostate cancer cell lines and treated with Dinaciclib. Zebrafish are a viable model for prostate cancer because they develop rapidly, have transparent embryos, which makes them easy to see under a microscope, and also lack an immune system within their first 10 days of life, decreasing the chance of rejection if they were to be given human cells.

My time in Porter Lab has been one of the most important and fulfilling experiences of my life because it has allowed me to grow not only as a scientist but also as a learner. I would like to express my sincere gratitude to my supervisors Dr. Lisa Porter and Dr. Elizabeth Fidalgo da Silva, as well as PhD and master’s students for their mentorship, encouragement, and guidance in developing my research ability. I wish the best of luck to the next group of thesis undergraduates!

Christopher Jaworski

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