Projects

Macrophages play critical roles in mediating host defense, inflammation, tissue remodeling, aging, and diseases such as atherosclerosis and cancers. The long-term research interest of Chen laboratory is to study the molecular mechanisms and the signal pathways in human macrophages in response to various stimuli including herbal extracts and the anti-inflammatory reagent adenosine. We employ both bioinformatics and functional genomics to integrate information into hypotheses and derived models. There are currently three active projects in progress:


Human monocytic THP-1 cells (left) and Agilent 44K whole human genome microarray (right)
(1) Human macrophage responses to herb extracts:
In recent years, it has been a great increase of use of herbal medicine in the Unites Sates, and currently herbal products are considered dietary supplements and are not required to submit proof of safety and efficacy before sale and marketing. From a scientific view, the antioxidants, phyto-hormonal compounds, and various chemicals found in herb extracts in principle may have substantial effects in the human body, and also possess great potentials for the prevention and treatment of diseases. Currently, we are focusing on understanding the molecular mechanisms by which feverfew functions in human macrophages. Feverfew traditionally been used for numerous symptoms including fever, women?s ailments, inflammation, psoriasis, toothache, insect bites, rheumatism, asthma and stomachache. During the last few decades, feverfew has been used for migraine prophylaxis. To gain insights and to generate new hypotheses, we have utilized oligonucleotide microarrays, in combination with real-time PCR (polymerase chain reaction) and molecular biology, to study the gene regulation by feverfew extracts in a model system, the human monocytic THP-1 cell line.

(2) The effects of adenosine on regulation of anti-inflammatory pathway:
Inflammation, a host response to infection or injury, is usually beneficial to the host. However, uncontrolled or prolonged inflammation can cause tissue and organ damage, and possibly lead to chronic diseases like atherosclerosis, rheumatoid arthritis, asthma, and cancers. Adenosine, released from leukocytes and endothelial cells, is an endogenous anti-inflammatory mediator that down-regulates acute inflammation in part by modulating macrophage cytokine production. We have identified approximately 1,400 genes that have significant changes in expression in adenosine alone- and adenosine in the presence of LPS- treated cells, compared to approximately 1,900 genes that have significant changes in expression in LPS-treated cells. Many of these have not been previously thought to participate in the anti-inflammatory process or have unknown function. We are investigating the functional roles of these genes.

(3) Integration of bioinformatics into functional genomics:
Bioinformatics is a combination of biology, computer science, informatics and information engineering. The challenge is to integrate the in silico insights of bioinformatics into the functional genomics and systems biology. We are using bioinformatics to identify (hidden) patterns and to produce new insights and hypotheses, and verify with experimental approaches. We implement data mining techniques and statistical methods for analysis of microarray data and are extending our studies into proteomics data. Two additional on-going sub-projects are: (a) developing statistical and computational methods for analysis signaling pathways and gene networks (with Dr. Feng Luo at Computer Science) and (b) developing new tools for mining public domain knowledge including GO (Gene Ontology), KEGG, and Reactome, and currently we are constructing an online tool to retrieve and visualize GO information and to measure the semantic similarity of GO terms (with Dr. James Wang at Computer Science).


Microarray analysis pipeline

Last Updated Friday, June 06 2008 @ 01:01 PM EDT; 5,249 Hits