CRISPRi screens to identify combination therapies for the improved treatment of ovarian cancer

Ovarian cancer is the fifth leading cause of cancer death for women in the United States, with only modest improvements in patient survival in the past few decades. Standard-of-care consists of surgical debulking followed by a combination of platinum and taxane agents, but relapse and resistance frequently occur. To identify genes that confer sensitivity or resistance in tumor cells treated with platinum chemotherapeutics, I performed genome-wide screens combining cisplatin or oxaliplatin with CRISPRi pooled gene knockdowns. Screens were analyzed at 9-days to mimic patient care, and at 48-hours to isolate the short-term DNA damage response. Genes whose knockdown caused sensitivity to the platinum chemotherapeutics were identified through a multi-objective optimization approach to account for knockdown efficiencies and variances in sequencing depth.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biological Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2021

Author dc:creator

• Handly, Erika Daphne.

Advisor dc:contributor.advisor

• Michael Yaffe.

• Biological Engineering.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/130803

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/130803