Yuxing Li

Professor

Yuxing Li Group

Contact

Email: yuxingli@umd.edu

Call: (240) 314-6332

Education

  • Postdoctoral Research, Viral Immunology, Vaccine Research Center, NIAID/NIH, 2008
  • Ph.D., Genetics, Iowa State University, 1996
  • M.S., Microbiology, Sichuan Industrial Institute of Antibiotics, The State Food and Drug Administration (SFDA), 1992
  • B.S., Genetics, Sichuan University, China, 1989

Profile

Dr. Yuxing Li’s lab studies how B cells, a critical part of the immune system, respond to viral infection, and applies these findings toward antibody discovery and the development of vaccines and therapeutics to treat viral infections.

Dr. Li’s work has focused on defining broadly neutralizing antibody responses elicited by HIV-1 envelope glycoproteins during natural infections and in animal models. These findings contributed substantially to the in-depth understanding of HIV broadly neutralizing antibody response and the subsequent discovery of broadly neutralizing monoclonal antibodies targeting the HIV envelope glycoprotein receptor binding site, and have important implications for vaccine and immunotherapeutics development.

Schematic Representation of the HIV-1 Envelope Glycoprotein (Env) Trimeric Spike. Shown is the molecular surface of the crystal structure of the core gp120 exterior Env (light blue) modeled inside the cryo-EM density (external blue sheen) defined by the Subramaniam group at the NIH. On the surface of the left most are the residue contacts for the human broadly neutralizing monoclonal antibody (mAb) VRC01 within the primary receptor CD4 binding site (yellow and orange). The Y-shaped VRC01 mAb (yellow) is able to access its epitope to the HIV-1 primary isolate spike and neutralize diverse viruses. The aim is to elicit VRC01-like antibody response in a vaccine setting (Sci Transl Med. (2012). 4, 142ra96). [FIGURE CREDIT: CHRISTIAN POULSEN AND CHRISTINA CORBACI, SCRIPPS RESEARCH INSTITUTE]

CURRENT RESEARCH

Development of B cell response targeting HIV-1 envelope glycoproteins (Env)

Dr Li’s work is focused on finding novel immunization regimens to better elicit broadly neutralizing antibodies. Dr. Li’s laboratory aims to better understand the mechanism underlying protective immunity and contribute to the development of a broadly effective HIV-1 vaccine.

Antigen-specific multi-color single B cell sorting and monoclonal antibody cloning

The Li lab is using rational design of HIV-1 (Env) immunogens and immunization regimens to analyze B cell and antibody responses with cutting-edge techniques. The Li lab is working to better define the B cell response to experimental HIV-1 vaccines toward discovering novel antibodies and gain insight into viral infection and vaccination.

Development of novel anti-viral immunotherapeutics by structure-based antibody engineering

Recently, Dr. Li’s laboratory successfully created a bi-specific antibody that combined functional epitope-binding moieties from two broadly neutralizing antibodies, VRC01 and PGT 121, which simultaneously binds two epitopes within one Env trimer and neutralizes >96% of circulating
HIV-1 isolates. Multi-specific antibodies developed based on this design demonstrated improved antiviral breadth and potency.

In close collaboration with Integrated Biotherapeutics, Inc., the Li lab successfully isolated a broadly neutralizing antibody, CA45, from an Ebola virus vaccine candidate, immunized, non-human primate animal and developed a pan-Ebolavirus therapeutic antibody cocktail for a pre-clinical trial in a non-human primate model. Therapeutic antibodies for Ebola virus infection were only protective against the Zaire Ebola strain but not other related filoviruses. The lab’s research focus is on understanding B cell responses to the filovirus glycoproteins to inform vaccine design to develop a broadly protective antibody response.

Negative staining EM of the Env trimer: bi-specific scFV complex showing that the bi-specific VRC01/PGT121 scFV cross-links the HIV Env trimer (Nat Commun (2018). 9,877.)

 

 

3D EM reconstruction of CA45 Fab (grey) bound to EBOV GPΔMuc structure (light blue, PDB 5JQ3) docked in (Cell (2017). 169, 891-904.e15).

                  

Publications
2021
Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities.
One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization.
Sulforaphane covalently interacts with the transglutaminase 2 cancer maintenance protein to alter its structure and suppress its activity.
Physiologically Relevant Free Ca2+ Ion Concentrations Regulate STRA6-Calmodulin Complex Formation via the BP2 Region of STRA6.
An Extract of Taro (Colocasia esculenta) Mediates Potent Inhibitory Actions on Metastatic and Cancer Stem Cells by Tumor Cell-Autonomous and Immune-Dependent Mechanisms.
1HN, 13C, and 15N backbone resonance assignments of the SET/TAF-1β/I2PP2A oncoprotein (residues 23-225).
The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile.
Prominent Neutralizing Antibody Response Targeting the Ebolavirus Glycoprotein Subunit Interface Elicited by Immunization.
Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint.
2020
1HN, 13C, and 15N resonance assignments of the Clostridioides difficile receptor binding domain 2 (CDTb, residues 757-876).
De novo protein design enables the precise induction of RSV-neutralizing antibodies.
Correction to: 1HN, 13C, and 15N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A transporter (CaMBP2).
HIV-1 gp120-CD4-Induced Antibody Complex Elicits CD4 Binding Site-Specific Antibody Response in Mice.
Structure of the cell-binding component of the Clostridium difficile binary toxin reveals a di-heptamer macromolecular assembly.
2019
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation.
Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo.
An asymmetry that leads to activity.
Second harmonic generation detection of Ras conformational changes and discovery of a small molecule binder.
A temperature-dependent conformational shift in p38α MAPK substrate-binding region associated with changes in substrate phosphorylation profile.
1HN, 13C, and 15N backbone resonance assignments of the human DNA ligase 3 DNA-binding domain (residues 257-477).