Kondapalli Lab

Our research is dedicated to unraveling the intricate dynamics of endosomal trafficking and its critical role in the functionality of multicellular organisms. Endosomes, acting as essential shuttles, play a pivotal role in orchestrating crucial cellular processes such as cell signaling, immune response, and nutrient uptake. At the core of our investigations is a fundamental question: what guides endosomes in the precise transport of cargo to specific locations within a cell? The significance of this inquiry lies in the potential consequences of misdirected cargo, which can contribute to various diseases, including cancer, Alzheimer's, and type 2 diabetes. Moreover, many viruses, such as SARS-CoV-2, influenza, and HIV, exploit the endocytic pathway for host cell entry and propagation. Understanding endosomal trafficking is not only vital for maintaining normal physiology but also crucial for developing effective strategies to combat diseases stemming from endosomal dysfunction. Building on our prior work, we have uncovered a novel role for endosomal pH as a guiding factor, resembling a GPS, steering endosomes towards specific destinations. A central focus of our research is the identification of molecular targets within the endocytic pathway that can selectively adjust luminal pH in endosomes. NHE9, a sodium-proton transporter, emerges as a promising target, subtly modulating luminal pH without drastic effects observed with other regulators. Our studies on receptor-mediated endocytosis provide a broader framework, offering insights into phagocytosis with notable parallels between these processes. These findings not only contribute to fundamental knowledge in cell biology but also hold therapeutic potential for addressing a spectrum of diseases associated with endosomal dysfunction.