A systems biology approach to investigate chemoresistance in urothelial carcinoma of the bladder.

To perform a complete molecular analysis of muscle invasive bladder cancer (MIBC) before and after pre-operative chemotherapy to find changes responsible for resistance to treatment. Analysis will include a combination of DNA sequencing, RNA expression analysis and quantification of protein. Together this information will reveal the molecular landscape for these tumors. We will use these complex datasets to address two specific comparisons: 1) chemotherapy responders versus chemotherapy non-responders (defined by extent of tumor remaining in bladder after chemotherapy); and, 2) tissue before and after pre-operative chemotherapy in non-responders, in order to assess for enriched molecular pathways that are indicative of resistance. Specific computer tools will be used to test the biologic functional of the changes described. The proposed methods include protein-protein interactions, gene-regulatory network and pathway-enrichment analysis. Novel analytic algorithms will also be developed to benefit the partner organization for day-to-day processing of clinical data.

Faculty Supervisor:

Peter Black

Student:

Akshay Bhat

Partner:

Genome Diagnostics

Discipline:

Medicine

Sector:

Life sciences

University:

University of British Columbia