Research

Overview

We study the structural and molecular mechanisms of viral infection and other diseases of global health concern, and develops therapeutic strategies.

Our primary research focuses on the invasion mechanisms of viruses with pandemic potential. We investigate viral surface proteins that mediate receptor recognition and cell entry, using structural and biochemical approaches, without growing or handling the viruses themselves.

Another area of our research explores the structural and molecular mechanisms of cancer and other human diseases. Specifically, we examine the structures and functions of human cell surface proteins that are critical for disease mechanisms.

Building on these structural and functional studies, we develop novel preventive and therapeutic strategies against viral infections and other human diseases.

Our research tools include X-ray crystallography, cryo-electron microscopy, protein biochemistry, vaccine design, and drug discovery.

Discoveries

Professor Li is a leading researcher in the coronavirus entry field. He has conducted pioneering work on the cell entry mechanisms of SARS-CoV-2 (COVID-19), SARS-CoV-1, MERS-CoV, and other coronaviruses. His group has solved many structures of coronavirus entry proteins (spikes), including the first seven structures ever reported in the spike-receptor field (2005-2012), and uncovered key molecular mechanisms by which these viruses invade host cells and transmit across species. His work has laid the foundation for the structural biology of coronavirus entry and has largely defined our current understanding of receptor recognition, cell entry, and cross-species transmission of coronaviruses.

Professor Li's research on COVID-19 has identified critical molecular strategies by which SARS-CoV-2 infects human cells and evades immune detection, while also shedding light on the virus’s evolutionary origins. These contributions have positioned his work as a leading scientific force in the global response to the pandemic.

In recent studies, Professor Li's research has uncovered novel mechanisms by which the highly lethal Ebola, Sudan, and Marburg filoviruses recognize their receptors, evade immune surveillance, and infect host cells.

Building on their discoveries in viral entry, Professor Li's group has developed novel nanobody- and small-molecule-based inhibitors targeting high-priority viruses, including SARS-CoV-2, Ebola, Sudan, and Marburg. His group also pioneered a structure-guided in vitro evolution platform to rapidly adapt nanobodies to newly emerging viral variants.

Beyond structural virology, Professor Li investigates the structural biology of cancer and other human diseases. His group has determined the structures of key enzymes that drive tumor growth and metastasis and is using these insights to develop new anti-cancer therapies. Overall, Professor Li’s goal is to translate fundamental structural discoveries into targeted therapies for human diseases.