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He Group Projects

We do both bioinformatics (dry-lab) and microbiology/immunology (wet-lab) biomedical research:

A. He Group bioinformatics projects:

Our bioinformatics research focus is to develop ontologies, ontology-based tools, databases, and analysis systems for addressign various biomedical questions. Our primary bioinformatics research has many topics:

  • Ontology development. Dr. He has initiated and led the development of the community-based Vaccine Ontology (VO) and Ontology of Adverse Events (OAE). VO and OAE can be used in many applications such as data integration and literature mining. We are also leading or collaborating the development of several other ontologies.
  • Ontology tool development. We have developed many ontology tools that are used for ontology reuse, ontology development, and ontology applications.
  • Literature mining, with a focus on ontology-based literature mining approaches.
  • Bayesian network (BN) modeling. BNs can model linear, nonlinear, combinatorial, and stochastic relationships among variables across multiple levels of biological organizations. We have developed new BN algorithms and tools for analysis of gene interaction networks using high throughput gene expression data.

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

  • Vaccine Informatics. We have developed the VIOLIN vaccine database and analysis system. As a part of VIOLIN, we 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. logy.
  • Comparative genomics. Various genome sequences can be compared to address many biomedical questions.
  • Bioinformatics analysis of host-microbe interactions. We are 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).
  • Analysis of vaccine and drug adverse event mechanisms. We are interested in applying the Ontology of Adverse Events to study the mechanisms of vaccine and drug-induced adverse events.

We have developed many web-based bioinformatics projects at the University of Michigan Medical School. Some example ones are introduced below:

BBP: Brucella Bioinformatics Portal: A gateway for Brucella researchers to search, analyze, and curate Brucella genome data originated from public databases and literature.
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 incorporates 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 literature. 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 integration and analysis of high throughput 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 predictions with temporal datasets.
OntoFox: A web-based system to support ontology reuse. OntoFox facilitates ontology development by automatically fetching ontology terms and their annotations from existing ontologies and saving the results in an importable RDF/OWL format.
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.
Vaccine Ontology (VO): The VO project is a community-based project with an aim to develop the 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.

 

B. Brucella wet-lab pathogenesis and immunology research:

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. Our Brucella research has two focuses:

1. Analysis of the caspase-2 cell death pathway and its role in Brucella pathogenesis and immunity.

Our studies first found that live attenuated rough Brucella strains (e.g., B. abortus cattle vaccine RB51 and B. suis vaccine candidate VTRS1) cannot survive inside macrophages and dendritic cells, and induce a new caspase-2-mediated proinflammatory cell death that is different from non-proinflammatory apoptosis or caspase-1-mediated pyroptosis (see references: Bronner, O'Riordan, and He, 2013; Li & He, 2012; Chen et al, 2011; Chen & He, 2009). We named such new cell death as "caspase-2-mediated pyroptosis". We also found that the caspase-2-mediated cell death exists in macrophages treated with etoposide, naphthalene, or anti-Fas (Bronner, O'Riordan, and He, 2013). Interestingly, virulent Brucella inhibits such cell death in infected macrophages (He et al, 2006) but not in dendritic cells (Li & He, 2012). Caspase-2 is critical in regulating cell death, DNA damage, stress, cancer, and microbial infections. Our research aims to elucidate the caspase-2-mediated proinflammatory cell death pathway and its biological effect on protective immunity against brucellosis. This study is currently conducted at a BSL2 laboratory.

2. Analysis of caspase-2-mediated immune responses induced by other vaccines

We hypothesize that caspase-2-mediated immunity is important not only to Brucella, but also to other pathogens. Currently we are testing how caspase-2 mediates the immune responses of macrophages infected by tuberculosis vaccine BCG.   


Your suggestions and comments are appreciated.

He Lab |Ontobee|OntoFox|OAE|VO|Genomesh|Ignet|miniTUBA|PHIDIAS|VIOLIN
He Group
University of Michigan Medical School
Ann Arbor, MI 48109
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