Medical University of South Carolina
About Us
We are a research laboratory at the Medical University of South Carolina, Charleston, focused on studying DNA repair proteins and the alterations of their variants. Our lab is a part of the Biochemistry and Molecular Biology Department and it is located in the Hollings Cancer Center building.
Our Latest Research
We recently conducted research on the impact of BRCA2 missense variants within the BRC repeats domain on RAD51 binding, sensitivity to platinum drugs and PARP inhibitors and genome instability. Our findings suggest that certain variants are associated with an increased risk of developing specific types of cancer.
Impact of BRCA2 missense mutations on protein localization
We conducted a study to investigate the impact of BRCA2 missense mutations in the DNA binding domain on cellular localization. Our results show that pathogenic missense mutations in the DNA binding domain of BRCA2 lead to cytosolic mislocalization and sensitivity to platinum drugs and PARP inhbibitors.
Distinct Binding of BRCA2 BRC repeats to RAD51
We disssected the biochemical and cellular properties of the BRC repeats tethered to the DNA binding domain of BRCA2. Our results suggest BRC5–8 region potentiates RAD51-mediated DNA strand pairing and provides complementation functions exceeding those of BRC repeats 1–4. Furthermore, BRC5–8 can efficiently repair nuclease-induced DNA double-strand breaks and accelerate the assembly of RAD51 repair complexes upon DNA damage. These findings highlight the importance of the BRC5–8 domain in stabilizing the RAD51 filament and promoting homology-directed repair under conditions of cellular DNA damage.
BRCA2 Variants of Uncertain Significance, the Challenges and Benefits to Integrate a Functional Assay Workflow with Clinical Decision Rules
In this review, we provide a brief overview of BRCA2 functions in HDR, describe how BRCA2 VUS are currently assessed in the clinic, and how genetic and biochemical functional assays could be integrated into the clinical decision process. We suggest a multi-step workflow composed of robust and accurate functional assays to correctly evaluate the potential pathogenic or benign nature of BRCA2 VUS. Success in this precision medicine endeavor will offer actionable information to patients and their physicians.