Yongqun "Oliver" He, DVM, PhD

Dr. He's laboratory performs dry-lab (bioinformatics lab) and wet-lab (microbiology and immunology lab) biomedical research, and is focused on the areas of bioinformatics, systems biology, host-Brucella interaction, and vaccine research.

The laboratory's primary bioinformatics research has many topics:

1. Ontology development. Dr. He has initiated and led the development of several community-based ontologies, including Vaccine Ontology (VO), Ontology of Adverse Events (OAE), Ontology of Genes and Genomes (OGG), and Interaction Network Ontology(INO). They are also leading or participating in the development of several other ontologies. These ontologies can be used in many applications such as data integration and literature mining.
2. Ontology tool development. Dr. He's lab has developed many ontology software programs, such as OntoFox and Ontobee, which are widely used for ontology reuse, ontology development, and ontology applications.
3. Literature mining, with a focus on ontology-based literature mining approaches.
4. Bayesian network (BN) modeling. BNs can model linear, nonlinear, combinatorial, and stochastic relationships among variables across multiple levels of biological organizations. The lab has developed new BN algorithms and tools for analysis of gene interaction networks using high throughput gene expression data.

The above and other bioinformatics approaches have been used primarily in the following research areas:

1. Vaccine Informatics. Dr. He's lab has developed the VIOLIN vaccine database and analysis system. As a part of VIOLIN, they have developed Vaxign, the first web-based publically available vaccine target design tool based on bioinformatics analysis of genome sequences using the strategy of reverse vaccinology.
2. Bioinformatics analysis of host-microbe interactions. The lab is interested in developing and applying bioinformatics methods to study the intricate interactions between host (e.g., human and mouse) and microbes (pathogens or bacterial microbiota).
3. Analysis of vaccine and drug adverse event mechanisms. The lab is also interested in applying the Ontology of Adverse Events to study the mechanisms of vaccine and drug-induced adverse events, and has conducted comparative genomics research.

Dr. He's wet-lab research is focused on the study of Brucella, a facultative intracellular bacterium that causes brucellosis, one of the most common zoonotic diseases in the world in humans and a variety of animal species. Current wet-lab Brucella research focuses on the analysis of caspase-2-mediated cell death mechanism and its role in Brucella pathogenesis and immunity. The lab's studies first identified a new caspase-2-mediated proinflammatory cell death, which exists in macrophages and dendritic cells infected with live attenuated rough Brucella strains (e.g., B. abortus cattle vaccine RB51 and B. suis vaccine candidate VTRS1) (see references: Bronner, O'Riordan, and He, 2013; Li & He, 2012; Chen et al, 2011; Chen & He, 2009). This type of cell death is different from non-proinflammatory apoptosis or caspase-1-mediated proinflammatory pyroptosis, so the lab named the cell death "caspase-2-mediated pyroptosis". Interestingly, virulent Brucella inhibits such cell death in infected macrophages (He et al, 2006) but not in dendritic cells (Li & He, 2012).

Based on the study of the RB51-macrophage interaction model, endoplasmic reticulum stress activates the inflammasome via NLRP3- and caspase-2-driven mitochondrial damage (Bronner et al, 2015). Caspase-2 is critical in regulating cell death, DNA damage, stress, cancer, and microbial infections. This research aims to continuously elucidate the caspase-2-mediated proinflammatory cell death pathway and its biological effect on microbial pathogenesis and protective immunity against brucellosis and other diseases. Dr. He's lab is also interested in the study of the roles of caspase-2 in host responses induced by other vaccines (e.g., tuberculosis vaccine BCG). The lab's current wet-lab vaccine mechanism research is conducted at a BSL2 laboratory.

For more information, please visit the He Laboratory Group website.