CRISPR/Cas9-mediated PARP1 disruption to sensitize BRCA1 mutated breast cancer cells in response to chemotherapy

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The purpose of this project is to exploit the relationship between BRCA1/2 mutations and the PARP1 gene to sensitize breast cancer cells to chemotherapy. CRISPR/Cas9 will be utilized to disrupt the PARP1 gene in wild-type and mutated breast cancer cell lines. The conditions for transfection will be optimized in terms of cell seeding density, time-scale, and delivery agent to achieve the greatest gene disruption efficiency. The consequential change in the IC50 of different chemotherapeutic agents will be tested in these two cell lines post gene disruption to assess the degree of synergy between the two treatment methods. Once the optimal chemotherapeutic is determined, the concept will be compared to conventional PARP inhibitor drugs in terms of cell viability. The treatment paradigm will be validated in a 3D microfluidic breast cancer model to gain further insight into its physiological and clinical relevance.

Lab: Nanotherapeutics and Stem Cell Engineering Laboratory

Direct Supervisor: Sima Lao

Position Dates: 5/14/2018 - 8/20/2018

Hours per Week: 40

Paid Position: No

Credit: Yes

Positions Available: 1

Qualifications: Cell culture, transfection, gel electrophoresis, genetic engineering

Eligibility: Sophomore, Junior, Senior, Master's; SEAS only

Professor Kam Leong: kamleong1@gmail.com