Interaction between host cell and pathogens. We use biochemical and cell biological approaches to understand the nature of interaction between different toxins and viruses with their host cell. Specifically, we are studying how cholera toxin and polyoma/SV40 virus hijack cellular machineries to cause disease. Both the toxin and viruses bind to receptors at the plasma membrane to initiate infection. The receptor-toxin or receptor-virus complex is endocytosed and traffic backwards along the secretory pathway to reach the lumen of the endoplasmic reticulum (ER). From this compartment, these toxic agents are transported across the ER membrane into the cytosol. Once in the cytosol, cholera toxin induces a signaling cascade which leads to massive water secretion resulting in diarrhea. Polyoma and SV40 virus, upon reaching the cytosol, are transported into the nucleus where transcription and replication of the viral DNA genome ensue, leading to infection of the host cell. How the toxin and the viruses are transported from the cell surface to the ER and subsequently transported out of the ER into the cytosol are processes that remain largely mysterious. Our overall goal is to clarify the cellular entry mechanism of both cholera toxin and polyoma/SV40 virus. Insights into these mechanisms will not only lead to a better understanding of how certain toxins and viruses infect their host cell, but will also clarify important aspects of basic cellular processes.