He Group Projects

Our primary biomedical research interest is to understand pathogenesis and immunology of infectious diseases and develop vaccines against intracellular pathogens. In particular, we study Brucella, a facultative intracellular bacterium that causes zoonotic brucellosis in humans as well as domestic and wild life animals. We have both microbiology/immunology (wet-lab) and bioinformatics (dry-lab) research projects.

A. Brucella pathogenesis and immunology research:

1. Brucella LPS and pathogenesis:

Unlike many pathogenic bacteria, Brucella lacks classical virulence factors such as invasive proteases, exotoxins, capsules, fimbriae, virulence plasmids, and lysogenic phages. Brucella virulence relies on its ability to survive and replicate within vacuolar phagocytic compartments of macrophages. Brucella lipopolysaccharide (LPS) is a virulence factor. Brucella LPS is resistant to intracellular degradation and several-hundred-time less toxic than E. coli LPS. Smooth B. abortus, B. melitensis, and B. suis are virulent while their corresponding rough strains, which are deficient in the LPS O-side chain (or called O antigen), are attenuated or avirulent. We are currently investigating the specific roles of Brucella LPS and O antigen in pathogenesis and the mechanisms of survival and replication by smooth but not rough Brucella strains.

2. Macrophage responses against Brucella infections:

Smooth virulent Brucella survive and replicate inside macrophages. Macrophages kill more than 90% of Brucella within the first 24 hours post infection; however, the surviving Brucella rapidly multiply afterwards. Virulent Brucella also inhibit  macrophage cell death. Rough attenuated Brucella strains cannot survive inside macrophages, and many of them induce severe programmed cell death of infected macrophages. Currently we are using microarrays to analyze differential and coordinate macrophage responses against smooth virulent and rough attenuated Brucella infections. Immunological and RNAi technologies are also used to study programmed macrophage cell death caused by rough Brucella mutants. 

3. Brucella subunit vaccine development:

Current cattle Brucella vaccine RB51 (invented by Dr. He's PhD advisor Dr. Gerhardt Schurig and his colleagues) has greatly contributed to the national brucellosis eradication program in the USA. However, no human Brucella vaccine exsits. Better understanding of Brucella pathogenesis and host immune responses allows rational design of safe and effective vaccines against brucellosis. One ultimate goal of our lab research is to develop a human Brucella subunit vaccine based on the state-of-the-art reverse vaccinology and adjuvant technologies.  

B. He Group bioinformatics projects:

Our bioinformatics research focus is to develop database and analysis systems for infectious disease research and studying biological networks (e.g., apoptosis) by Bayesian network modeling, microarray data analysis, and literature mining. We have developed many web-based bioinformatics projects at the University of Michigan Medical School:

	CRCView: A web-based microarray data analysis and visualization system, powered by a model-based clustering algorithm Chinese Restaurant Cluster (CRC) developed by Dr. Steve Qin. CRCView also incoporates several Bioconductor microarray analysis programs including GOStats, genefilter, and Heatplus.
	GenoMesh: a genome-wide analysis of gene-to-gene relationships and pathways based on the association between individual genes and MeSH terms obtained from literatrue. Currently GenoMesh includes data on Escherichia coli and Brucella spp..
	MARIMBA: Molecular Annotation Resource for Integrating Microarray with Bayesian Analysis -- a web-based Bayesian network modeling system for integratation and analysis of microarray gene expression data.
	miniTUBA: Medical Inference by Network Integration of Temporal Data Using Bayesian Analysis -- a web-based dynamic Bayesian analysis engine for clinical and biomedical researchers to perform medical inference and prediction using temporal datasets.
	BBP: Brucella Bioinformatics Portal -- a gateway for Brucella researchers to search, analyze, and curate Brucella genome data originated from public databases and literature.
	PHIDIAS: Pathogen-Host Interaction Data Integration and Analysis System -- a web-based data integration and analysis system for biomedical researchers to investigate genomic sequences, curated literature information, and gene expression data related to pathogen-host interactions for those pathogens with high priority in public health and biological defense.
	Vaccine Ontology (VO) -- The VO project is a community-based project with an aim to develop the Vaccine Ontology (VO) to ensure vaccine data standardization, exchange, and automated reasoning.
	VIOLIN: Vaccine Investigation and Online Information Network -- a web-based database system for research and development of vaccines against various human pathogens (e.g., HIV, influenza, and tuberculosis) with high priority in public health and national biological defense.

Your suggestions and comments are appreciated.