William Wan, Ph.D.

Research

The Wan lab will explore how the Ebola virus gains entry into host cells. For any virus, the first step of infection involves entering into the cells of the host. To accomplish this task, a virus must attach to receptors on the surface of host cells, trigger internalization, and then break free of the compartment in which it was encased when the host cell took it in. For Ebola, one key part of this process is a viral glycoprotein called GP. Despite this, precisely how GP interacts with host proteins to engineer its entry into host cells is poorly understood. This is partly due to the challenge of working with such a deadly and contagious virus as well as the difficulty in visualizing the extremely small scales at which proteins interact. Furthermore, it is becoming apparent that another process, called apoptotic mimicry, plays a significant role in viral entry. Apoptosis is a form of controlled cell death, which results in clearance of damaged cells by neighboring healthy cells. In apoptotic mimicry, viruses disguise themselves as damaged cells to gain entry by exploiting normal apoptotic clearance mechanisms. To study how GP and apoptotic mimicry work in concert, my lab will use powerful new techniques in molecular, cell, and structural biology to study the interaction between Ebola virus and host cells. My lab will generate virus-like particles that possess the key molecular components of Ebola, including its all-important GP, but lack active viral genes, making them safer to study in the lab. Then, using advanced molecular imaging techniques on these particles, we will characterize how they interact with host cell receptors, how they initiate internalization, and how they are processed once inside. These findings will uncover novel targets for combating Ebola and other viruses that deploy similar mechanisms for infecting hosts.