Study of altered metabolism in cancer by high content SRS microscopy

Altered metabolism represents an Achilles' heel of cancer, offering opportunities for advanced diagnosis and treatment. However, studying cancer metabolism at the single-cell level remains challenging. Current methods are either destructive and provide only bulk analysis, like mass spectrometry, or require fluorescent labeling that can perturb metabolic processes. Recently developed high-content, high-resolution SRS microscopy enables single-cell metabolic analysis and I successfully applied this approach to identify and target metabolic pathways in cancer therapy contexts.In the first project, I applied high-content SRS imaging to study metabolic changes in ovarian cancer cells surviving the CAR-T challenge. CAR-T therapy shows promise in liquid tumors but faces significant challenges in solid tumors like ovarian cancer. I used drug interventions to improve CAR-T cytotoxicity based on the identified metabolic alterations. In the second project, I used isotope-probed SRS imaging to visualize fatty acid distribution differences between wild-type ovarian cancer cells and those resistant to platinum treatment. I examined subcellular localization at lipid droplets and ER membrane levels to identify the affected cellular components. I then followed up with tissue-level analysis of triglyceride changes in cellular regions of xenograft models treated with fatty acid inhibitors combined with platinum therapy. The third project demonstrates the development of high-content SRS histology that provides both morphological information like conventional histology and detailed chemical information at the cellular level in breast cancer tissues, with potential applications to other cancer types. Together, the work in my dissertation shows that advanced SRS imaging can reveal metabolic reprogramming during cancer therapy and identifies specific metabolic vulnerabilities that can be targeted to improve treatment efficacy. The methodological advances developed here enable studying metabolism-based therapeutic strategies across multiple cancer types and treatment approaches.

Author dc:creator

• Prabhu Dessai, Chinmayee Vallabh

Advisor dc:contributor.advisor

• Cheng, Ji-Xin

• Biomedical engineering
• Cellular biology
• Histology
• Breast cancer
• CAR-T therapy
• Chemical imaging
• Ovarian cancer
• Stimulated Raman histology
• Tissue imaging

Statement dc:rights

• Attribution 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/2144/51142

OAI identifier oai:identifier

oai:open.bu.edu:2144/51142