Meng Yuan, PhD

My research mainly focuses on molecular understanding of antibody–antigen interactions by investigating the structural basis of antibody recognition of microbial pathogens. We have structurally characterized many viral targets including coronavirus spike proteins, mpox surface proteins, HIV-1 envelope glycoprotein, as well as their complexes with host receptors and many antibodies. We have discovered public clonotypes of neutralizing antibodies against the viruses, and provided structural understanding of such antibodies being naturally favored against the viral targets. 

Structural basis of antibody recognition of viruses
Recognition of viral antigens by the immune system is essential for protection against infectious diseases. Our research aims to elucidate how antibodies recognize and neutralize these antigens through high-resolution structural studies. We have determined over 70 structures of neutralizing antibodies targeting various regions of SARS-CoV-2 spike (S) protein and constructed an epitope map that delineates the relationship between viral vulnerability and variability. We are also actively investigating novel protective epitopes on the SARS-CoV-2 S protein. Additionally, structural studies of the HIV-1 envelope protein in complex with broadly neutralizing antibodies aim to inform rational vaccine design strategies. We are also interested in identification and characterization of neutralizing/protective antibodies and epitopes against mpox virus, and antibody combinations, to provide critical insights to improve therapeutic options against present and future mpox and other poxvirus outbreaks.

Public antibodies and antibody allelic polymorphisms

Identifying public antibodies is critical for germline-targeting vaccine design. Our research focuses on analyzing public antibody classes elicited by diverse antigens, and understanding their structural convergence. In addition, the capacity of the human immune system to generate antibodies against specific antigens can be strongly influenced by immunoglobulin allelic polymorphisms. We are investigating the diversity of human immunoglobulin alleles and assessing how allelic variation affects antibody recognition and immune response.

Functional and structural studies of phospholipase D3 and D4

Phospholipase D3 and D4 (PLD3 and PLD4) play critical roles in regulating sensors of innate immunity. We demonstrated that these enzymes function as exonucleases that cleave single-stranded nucleic acids, and we determined structures of mammalian PLD3 and PLD4, revealing a two-step catalytic mechanism. We are further investigating how 5'-phosphated nucleotides found in certain RNA virus constrain the catalytic efficiency of PLD3 and PLD4. 

Complete List of Published Work in My Bibliography