Cancer Biology

Can decoding the molecular mechanisms of PKM2 pave the way for more effective cancer therapies?

At ABC Lab, we seek to answer this question by elucidating the atomic-level mechanisms that govern PKM2 structure, conformational dynamics, and catalytic efficiency, with the ultimate goal of enabling the rational design of next-generation therapeutics targeting cancer metabolism. PKM2 serves as a central regulator of cellular metabolism, orchestrating the balance between energy production and biosynthetic pathways essential for cell survival and proliferation. In cancer cells, aberrant regulation of PKM2 rewires metabolic networks, promotes the Warburg effect, and supports tumor growth, making it one of the most promising therapeutic targets in cancer metabolism.

Our research aims to decipher how allosteric regulation, post-translational modifications and mutations reshape PKM2 structure and function. By uncovering the molecular basis of these regulatory events, we seek to understand how subtle structural perturbations propagate across the protein to alter catalytic activity and cellular metabolism. To achieve this, we integrate molecular dynamics simulations, QM/MM calculations, and structure-based drug discovery to investigate PKM2. These complementary approaches enable us to bridge the gap between fundamental enzymology and translational drug discovery, accelerating the development of novel therapeutics for cancer.

MicroRNA regulation in Cancer

MicroRNAs (miRNAs) are small non-coding RNAs that regulate cancer by acting as either tumor suppressors or oncogenes. Downregulation of tumor-suppressor miRNAs leads to oncogene activation, while overexpression of oncogenic miRNAs inhibits tumor-suppressor genes, collectively driving tumor initiation, progression, angiogenesis, metastasis, and therapeutic resistance.

 Impact of DEmiRNAs on Hallmarks of Cancer

MicroRNAs act as key post-transcriptional regulators of gene expression, controlling diverse cellular processes such as proliferation, apoptosis, differentiation, angiogenesis, metabolism, and immune responses. Their dysregulation contributes to the initiation and progression of numerous diseases, particularly cancer, where they influence tumor development, progression, metastasis, and therapeutic response. These characteristics make miRNAs promising biomarkers and potential therapeutic targets for precision medicine.