Sepideh Soukhtehzari
Doctor of Philosophy in Pharmaceutical Sciences (PhD)
Research Topic
Identification of polysialylated proteins in breast cancer and correlation with patient prognosis
Karla Williams
Associate Professor
Relevant Thesis-Based Degree Programs
Great Supervisor Week Mentions
Each year graduate students are encouraged to give kudos to their supervisors through social media and our website as part of #GreatSupervisorWeek. Below are students who mentioned this supervisor since the initiative was started in 2017.
Dr. Karla Williams, a great supervisor and a super great human being, is one of the most inspiring personalities I ever came across. When I started my PhD. in September 2017, the first few months were very challenging for me. Dr. Williams worked on me and helped me regain my momentum. Working under her supervision is a true blessing I cherish every day.
Graduate Student Supervision
Doctoral Student Supervision
Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
Nanoscale flow cytometry for extracellular vesicle analysis and isolation (2023)
Extracellular vesicles (EVs) are nanosized (~30-1000 nm) lipid-enclosed particles released by all cell types. The cargo contained within the EV is representative of the cell of origin containing lipids, proteins, glycans, and nucleic acids. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. Direct enumeration of tumor-derived EVs and/or profiling of their molecular cargo in patient body fluids have been shown to provide valuable information about the biology of the tumor. Given their nanosized properties, EVs are difficult to isolate and study. In complex biological samples, this difficulty is amplified by other small particles and contaminating proteins making the discovery and validation of EV-based biomarkers challenging. Developing new strategies to analyze and isolate EVs from complex biological samples is of significant interest. This thesis focuses on developing nanoscale flow cytometry for EV analysis and isolation in the context of prostate cancer. Prostate cancer screening strategies have not advanced since the introduction of the Prostate Specific Antigen (PSA) blood test, despite prostate cancer being the most commonly diagnosed cancer in Canadian males. Relying on imprecise detection methods, such as the PSA blood test, has deeply hampered our ability to detect and treat clinically relevant prostate cancer early, which is the most important factor for decreasing mortality rates. Therefore, alternative, non-invasive biomarkers capable of identifying high-risk prostate cancer are urgently needed to improve the detection and prognostication of prostate cancer patients. iv The work described in this thesis utilizes nanoscale flow cytometry to enumerate circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of prostate cancer patients and healthy males and demonstrates a diagnostic capability far superior to the PSA blood test. To improve the prognostication capabilities of our test and detect high-risk prostate cancer, we then developed a method to isolate subpopulations of EVs directly from human plasma using nanoscale flow cytometry without additional EV isolation strategies. The isolation and enrichment of unique EV populations have significant implications in the discovery and validation of biomarkers with clinical utility.
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Developing models to study breast cancer progression and investigating the role of invadopodia in tumor cell metastasis (2022)
The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
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Master's Student Supervision
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
CCR7 localizes at invadopodia and promotes tumor cell dissemination through a lymphatic endothelium (2023)
Breast cancer is the most commonly diagnosed cancer globally, where around 34% of patients will develop metastatic breast cancer with only 22% survival rate over five years. Individuals who develop metastatic breast cancer patients have limited effective treatment options. To improve treatment options, a better understanding of metastatic disease is needed. Studies focused on understanding the process of tumor cell metastasis will result in improvements to our understanding of tumor metastasis and may identify novel disease drivers that can be drug targets. Here, this thesis aims to investigate tumor cell dissemination as regulated by small sub-cellular structures called invadopodia. Invadopodia are specialized actin-rich membrane protrusions that aid in tumor cell dissemination and invasion. Invadopodia have been shown to degrade the extracellular matrix to invade surrounding tissues and facilitate the entry and exit through blood vessels. We investigated the role of invadopodia in driving tumor cell invasion through a model of the lymphatic endothelium. Invadopodia were found to mediate this process and further investigation into invadopodia-based drivers of this process identified CCR7 as a mediator. CCR7 is a chemokine receptor that is known to home the dendritic cells to the lymph nodes, and has two endogenous ligands CCL19 and CCL21. In our model, tumor cells were responsive to CCL19 and this promoted invadopodia formation and increased invasion through a lymphatic endothelium model. Overall, this study has advanced our understanding of invadopodia-associated tumor cell dissemination via lymphatics, and provides insight into a mechanism of CCR7-mediated invadopodia invasion.
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The role of GABA-mediated actin cytoskeletal dynamics in driving invadopodia formation and tumour cell invasion (2022)
The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.
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Current Students & Alumni
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