Peter Black

Professor

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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.

Genome-wide CRISPR screen to determine molecular mechanisms of cisplatin resistance in muscle-invasive bladder cancer (2020)

Bladder cancer is the 5th most common cancer in Canada and an estimated 9,000 Canadians are diagnosed with bladder cancer each year. Cisplatin-based Neoadjuvant chemotherapy (NAC) followed by radical cystectomy in patients with muscle-invasive bladder cancer (MIBC) has been shown to improve five-year survival, and is therefore currently the first-line standard of care in patients. However, 60% of patients are inherently resistant to NAC at the time of cystectomy. Several mechanisms of cellular resistance to cisplatin have been proposed, however, the mechanisms presented thus far still do not offer and effective patient response prediction in the context of MIBC. As such, in order to elucidate mechanisms of resistant to cisplatin, the study presented in this thesis takes advantage of a pooled genome‐wide CRISPR knock‐out library targeting 19,114 protein coding genes with 76,441 synthetic guide RNAs (sgRNAs) which allows for an unbiased screen.We first established the capacity to carry out a pooled genome-wide CRISPR screen by optimizing screening conditions. A full-scale screen revealed that several genes involved in the pro-apoptotic pathway (such as CASP8, BAX, and TNFSFR10A) and cell cycle regulation have the potential to confer resistance to cisplatin when knocked out. For this study, we validated the top hit from our screen, SLFN11, and established that the loss of SLFN11 confers a cisplatin resistant phenotype in MIBC. Overall, the study presented here offers SLFN11 as a potential biomarker to aid in clinical decision making and to anticipate resistance to cisplatin-based NAC in MIBC. Further, targeting SLFN11 associated pathways could allow for the development of combination therapies to be used in conjunction with cisplatin in the future.

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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.

Percutaneous nephrostomy versus retrograde ureteral stent in adult patients with malignant ureteral obstruction : comparing changes in the renal function and clinical outcomes (2023)

Background: Urinary diversion (UD) in malignant ureteral obstruction (MUO) is required to relieve symptoms, initiate systemic therapies, and save lives, especially in bilateral ureteral obstruction. Percutaneous nephrostomy (PCN) and retrograde ureteral stent (RUS) are the most common interventional methods. However, these interventional methods' success, efficacy, and complication rates vary. Methods: Clinical outcomes and changes in renal function following UD in patients with MUO treated at Vancouver General Hospital (VGH) from January 2015 to October 2021 were analyzed retrospectively. A total of 159 patients were identified, of whom 81 underwent PCN (38 males (46%) and 43 females (53%), mean age ± SD 65.7± 12.9 years, range 35 to 95 years) and 78 underwent RUS insertion (27 males (35%) and 51 females (65%), mean age 66.4 ± 13.1 years, range 24 to 90 years). Renal function changes were compared between the two groups using serum creatinine and estimated glomerular filtration rate (eGFR) data at baseline, at intervention, and at different time points after intervention (1 week and 1,3,6, and 12 months). Clinical endpoints assessed included the success rate of UD, procedural complications, and the need for another UD method. Results: The renal function was comparable between the two study arms except at the time of the intervention, in which the PCN median creatinine was 290 vs 127 in the RUS (p
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Induction of epithelial-to-mesenchymal transition (emt) causes resistance to trail-mediated cell death in bladder cancer (2020)

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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