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Specialized Center of Interdisciplinary Research (SCOR)

 

Genomic Convergence for Female Osteoporosis Risk Genes


 

Projects & Cores

 

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SCOR Overview:

In this SCOR project, we use a highly inter-disciplinary approach of genomic convergence to identify genes and some of their functions that are important to risk of osteoporosis in females. Female specificity of the identified genes will be examined in male samples. In addition, we will examine potential population/ethnic generality/specificity of the genes identified from this project. Finally, we will investigate the specific functional mechanisms of the identified genes on bone metabolism.

Identifying genes for human bone mineral density (BMD) variation, especially for women, is important for 1) gaining insights into the fundamental molecular mechanisms of risk to osteoporosis, 2) discovering new pathways and targets for therapeutic cures; 3) designing molecular markers and diagnostic chips for identifying genetically susceptible individuals, so that future preventions and interventions can be targeted to and based on individuals' specific genotypes via personalized medicine.

Current SCOR Research Projects


Project 1:  Genome wide scans for female osteoporosis genes

PI: Yongjun Liu, M.D., Ph.D., Tulane University 

Co-I: Hui Shen, Ph.D., Tulane University

Osteoporosis is the most prevalent metabolic bone disease and a major public health problem mainly characterized by low BMD. BMD has a heritability > 60%. The specific genes involved are largely unknown. Women have lower BMD and higher risk to osteoporosis than men. The goal of this project is primarily to identify such osteoporosis genes for females and, secondarily, to assess the gender specificity of these identified genes in male samples. We will perform a powerful genome wide association study (GWAS) using the latest Affymetrix SNP chips for a large sample of US Caucasian subjects including both females and males. We will compare the results obtained from the GWAS with our previous linkage studies and gene/protein expression data (including those to be obtained in Projects 2 and 3 of this SCOR) and other available data of in vivo and in vitro studies. The most significant findings will be replicated in other populations to assess their ethnic generality or specificity.


Project 2:  Genome-wide differential gene expression study of osteogenic cells in females

PI: Yao-Zhong Liu, M.D., Ph.D., Tulane University

Co-I: Ming Zhao, M.D., Ph.D., Tulane University

Osteoporosis is a major public health problem, especially in women. It is mainly characterized by low BMD. 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 will recruit 80 otherwise healthy females, stratified by discordant BMD values and menopausal status. We will perform bone marrow aspiration and obtain peripheral blood samples. BMMSCs and PBMs will be isolated and total RNA extracted. Microarray profiling experiments and analyses will be performed on each subject for >40,000 known human genes and ESTs. Differentially expressed genes will be verified by real-time RT-PCR.


Project 3:  Proteome-wide expression study of osteogenic cells

PI: Hong-Wen Deng, Ph.D., Tulane University

Co-I: Fei-Yan Deng, Ph.D., Tulane University

Osteoporosis is a major public health problem, especially in women. It is mainly characterized by low BMD. 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 protein 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's health in general. We will recruit 80 otherwise healthy females, stratified by discordant BMD values and menopausal status. We will perform bone marrow aspiration and phlebotomy on each subject. BMMSCs and PBMs will be isolated, and total protein will be extracted. Proteome-wide protein expression profiling experiments and analyses will be performed on each sample using LC-nano-ESI-MS/MSE methodology. Differentially expressed genes will be verified by western blotting.


Administrative core

Director: Hong-Wen Deng, Ph.D., Tulane University

Assistant Director: Yongjun Liu, Ph.D., Tulane University 

The main objective of the Administrative Core is to provide leadership, coordination of interactive and collaborative effort, managerial (personnel and budgetary) support, and facilitation for the overall operation of the SCOR.

Clinical core

Director: Yongjun Liu, M.D., Ph.D., Tulane University

Co-Director: Yaozhong Liu, M.D., Ph.D., Tulane University

Co-I: Lan-Juan Zhao, Ph. D., Tulane University

This SCOR Program aims at identification of female osteoporosis risk genes using the genomic convergence approach. The overall objective of this Clinical Core is to recruit 80 females (40 high vs. 40 low BMD, with ½ pre- and ½ postmenopausal subjects in each BMD group) to support work in SCOR Projects 2 and 3. Steps in specimen collection are:

  • perform phlebotomy to obtain 130 ml peripheral blood;
  • schedule for bone marrow aspiration;
  • perform 20 ml bone marrow aspiration;
  • transport the specimens immediately to the laboratory for isolating peripheral blood monocytes and bone marrow mesenchymal stem cells for downstream experiments for SCOR Projects 2 and 3. 

 

Biostatistics and bioinformatics core

Director: Hong-Wen Deng, Ph.D., Tulane University

Associate Director: Jian Li, Ph.D., Tulane University

Our Biostatistics and Bioinformatics Core will essentially serve as a resource and collaboration synergizer for all individual projects of the SCOR.

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