Research Projects

Breast cancer is a major global health concern. Noteworthy, it is predicted that breast cancer will cause more deaths than any other melodies in developing countries including India. Therefore, there is an urgent need for more advanced breast cancer healthcare that addresses current health concerns and prepares for future challenges, ensuring sustainable growth and development for Swasth Viksit Bharat. Of note, in India, the triple-negative breast cancer (TNBC) subtype is mainly causing heightened morbidity and mortality rates compared to those in Western European countries. Thus, under the PM-ECRG proposal, my goal is to develop a rapid, patient-specific pre-clinical assessment of cancer drugs and a stratification platform for the coastal population of Dakshina Karnataka admitted to Justice KS Hegde Charitable Hospital. Further, this will be coupled with the invention of novel therapeutic strategies for TNBC patients, which will be validated using human clinical samples and in vitro cell-line models. The origin of the current proposal stems from the preliminary data recently generated in the lab, which reveals a significant overexpression of NSMCE2 E3 SUMO ligase molecule in tumor biopsies. However, the biological and clinical significance of its amplification in breast cancer pathogenesis and chemoresistance remains largely unknown. Therefore, by investigating the critical knowledge gap, we aim to bridge the basic science and translational use of NSMCE2 molecule as both a biomarker and a novel therapeutic target. Building on my expertise in the field of breast cancer research, we will aim for three specific objectives during the three years of the project: 1) To develop a rapid protocol for the assessment of cancer drugs in cultured cells derived from patients' biopsies for clinical decisions and study the effect of NSMCE2 targeting. 2) To dissect molecular mechanisms of NSMCE2-associated SUMOylation signaling pathway using in-vitro cell line model systems, thereby delineating the roles of NSMCE2 in tumor cell survival and chemoresistance. 3) To bridge the basic science of NSMCE2 molecule with clinical samples to discover novel therapeutic strategies for breast cancer. Results obtained during the project will have an immediate impact on multiple dimensions of breast cancer research and diagnostics. For instance, demonstrating NSMCE2’s critical roles in DNA damage repair and replication fork dynamics under pharmacological drug treatments conferring chemoresistance will result in high-quality research publications and patents. More importantly, establishing NSMCE2 as a novel diagnostic marker will improve clinical decisions for Indian patients by enabling early breast cancer detection, patient stratification, and the development of precision medicines. Together, the knowledge produced during the project would lay a strong foundation for future grant proposals for the lab accelerating efforts to bridge basic research and translational research.