Bhakat Lab

Tumor recurrence and metastasis remain the major clinical challenges for cancer treatment. Ionizing radiation (IR) and chemotherapies have been the first line of care for treatment of many types of cancers including brain and pancreatic cancer. These conventional cytotoxic therapies cause DNA damage and induce cell death. Although this standard of care has significantly improved the overall survival rates, high doses of chemo and IR are associated with long-term toxicities in surviving patients. Moreover, postsurgical residual tumor in some groups of patients rapidly develop therapy-resistant which often leads to tumor recurrence and distal metastasis. The major goals of our lab are to understand the molecular mechanisms that alter the damage repair pathways and gene expression in tumor cells to promote therapy resistance and tumor recurrence and develop second line of interventions to prevent tumor recurrence and metastasis and improve the quality of life of patients.

We have recently discovered a novel mechanistic connection between elevated levels of a DNA repair protein APE1, a histone chaperone FACT complex and G-quadruplex (G4), a non-canonical (non-B form) four-stranded DNA secondary structure in promoting therapy-induced damage repair and gene expression. Our research goals are to elucidate how these factors work together to promote resistance to radiation and chemo and develop targeted multifunctional nanoparticles (NP) loaded with chemo or radiosensitizers to target therapy resistance tumor cells and prevent tumor recurrence and metastasis in a preclinical model.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) among all the BC subtypes due to its exceptionally high metastasis rate. TNBC patients with metastasis have a short overall survival as the endocrine therapy and chemotherapy are inefficient in TNBC treatment. Studies have revealed that G4 DNA is highly enriched in TNBC signature genes’ promoters, and our lab was the first one to uncover that DNA repair protein APE1 binds to G4 and regulates its stability in cells. We are interested in elucidating the interaction between APE1 and G4 in TNBC and their roles in regulating TNBC metastasis and targeting APE1-G4 interaction as a potential therapeutic approach to inhibit TNBC metastasis.

Full list of publications.