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Functional Genomics Study of Osteoporosis
 

Research focuses:

Our research is primarily focused on functional genomics study of osteoporosis. The major approach for the study is DNA microarray-based research that assays gene expression at the whole transcriptome level. Currently, under the support of an NIH SCOR Program Project "Genome-wide and Specific Gene Expression Study of Osteogenic Cells", we are performing a DNA microarray study of peripheral blood monocytes (PBMs) and bone marrow mesenchymal stem cells (BMMSCs) in subjects with osteoporosis (i.e., low bone mineral density (BMD)) and healthy controls (i.e., those with high BMD). PBMs and BMMSCs are precursors of osteoclasts (bone resorption cells) and osteoblasts (bone formation cells), respectively. By comparing genome-wide gene expression of PBMs and BMMSCs in subjects with high vs. those with low BMD, we are hoping to identify those genes and genetic pathways associated with osteoporosis.

 


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Another area of our research is genetic study of periodontitis. Periodontitis is a dental disease characterized by chronic and progressive loss of periodontal tissue (connective tissue that supporting the teeth) and oral bone. Under the support of an NIH RC2 project, we are performing a pilot study to extract and quantitate genomic DNA from buffy coat samples from periodontitis subjects and normal controls, which are provided by our collaborators, Dr. Robert Genco's group at University of Buffalo. This study will make preparation for an incoming genome-wide association study of periodontitis.


Personnel:

Studies:


 

Genome-wide gene expression study of osteogenic cells for osteoporosis

Osteoporosis is a major public health problem, especially in women. It is mainly characterized by low bone mineral density (BMD). Women have much lower BMD than men. Some BMD genes/genomic regions are sex-specific. Menopause is associated with rapid bone loss. 


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Bone marrow mesenchymal stem cells (BMMSCs) and peripheral blood monocytes (PBMs), are precursors for osteoblasts (bone formation cells) and osteoclasts (bone resorption cells), respectively.The GOAL of this project is to identify genes that are differentially expressed (at mRNA levels) in BMMSCs and PBMs in females with low vs. high BMD and with menopausal status changes. Such genes are expected to be important for variation of female BMD and women health in general.

We are recruiting otherwise healthy females aged 50-55, stratified by discordant BMD values and menopausal status. Bone marrow aspiration and phlebotomy will be performed on the recruited subjects to isolate BMMSCs and PBMs. Total RNA will be extracted from the isolated cells. Using the total RNA extracted, microarray profiling experiments and analyses will be performed for >40,000 known human genes and ESTs to identify differentially expressed genes/ESTs in low vs. high BMD subjects, which will be further verified with real-time RT-PCR.

As preliminary studies for this project, we have published several papers on microarray profiling of PBMs in high vs. low BMD subjects (J Biol Chem. 2005 12;280(32):29011-6; J Bone Miner Res. 2010 25(2):339-55; Bone. 2009 44(5):1010-4). These studies have identified several interesting genes/proteins important to osteoporosis.


 

Genome-wide association study of periodontitis

Periodontitis, characterized by progressive loss of periodontal attachment and alveolar bone, is one of the most prevalent chronic diseases and a major cause for loss of permanent teeth in the US. Periodontitis affects ~35% of the US adults over the age of 30 years.

Pathogenesis of periodontitis is complex, with multiple contributing factors, such as life styles, nutrition, systemic diseases, and medications etc. Among these factors, genetic determination is most important as evidenced by a high heritability of ~50% for periodontitis. However, specific genes underlying periodontitis are currently unknown.

With recent significant advances in densely spaced SNP identification, high-throughput genotyping technologies, improved knowledge of linkage disequilibrium (LD) patterns and haplotype structure across the human genome, genome-wide association studies (GWAS) have now become a feasible and powerful strategy for genetic dissection of human common diseases.

 

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Our general hypothesis is that risk genes for periodontitis can be detected with a powerful GWAS. To make preparation for such a GWAS, under the support of an NIH RC2 grant, we are performing a pilot study to extract and quantitate genomic DNA from buffy coat samples from periodontitis subjects and normal controls, which are provided by our collaborators, Dr. Robert Genco's group at University of Buffalo.

 

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Department of Biostatistics, 1440 Canal Street, Suite 2001, New Orleans, LA 70112, 504-988-5164 kbranley@tulane.edu