Researchers at Tulane’s Center for Bioinformatics and Genomics are digging deep to uncover the genetic underpinnings of complex conditions such as osteoporosis, periodontal disease, obesity, and alcoholism. As the research proceeds, the faculty of the center hope not only to discover new targets for drug development and prevention but also to refine and define the best practices for epigenetic research.
The newly-minted center facilitates multidisciplinary research in bioinformatics, biostatistics, computational biology, genetics, genomics, and proteomics. Researchers draw on tools from these fields to better understand the ways in which genetic risk, environment, and lifestyle factors may contribute to or protect from the development of a health condition.
Epigenetics – the study of the interplay between genetic risk and the factors that can affect health – is at the forefront of public health research and prevention efforts. The center’s research efforts span the globe, with collaborations extending from Yale University to China.
The center is divided into sections that focus on different aspects of genomics, such as epigenetics and epigenomics. Director Hong-Wen Deng also is chair of the Department of Biostatistics and Bioinformatics at Tulane’s School of Public Health and Tropical Medicine. He holds an endowed Chair in Biostatistics, funded by the Edward G. Schlieder Educational Foundation. Deng came to Tulane in 2011 to establish the center and continue his team’s research in New Orleans.
Deng is an internationally recognized researcher in statistical, quantitative, and population genetics and bioinformatics, and on genetics and genomics research of complex disorders. Prior to arriving at Tulane, he taught and conducted research at the University of Missouri at Kansas City. While there he held positions including director of the genetics program, director of orthopedic research, and the Franklin D. Dickson/Missouri Endowed Chair in Orthopedic Surgery.
The center, which currently has 15 faculty members, nine students, and seven postdoctoral researchers, aims to grow with the addition of new research projects and faculty whose expertise supports the growing research goals.
“Different sections focus on different areas, such as DNA balance or polymorphisms associated with disease risk,” explains the center’s associate director Hui Shen, assistant professor in the Department of Biostatistics and Bioinformatics. “Others focus on functional genomics and we recently expanded into epigenetics and epigenomics. We also try to combine the data to have a general model of how different aspects interact and work together to contribute to disease risk.”
The center’s work relies on high-caliber technology and statistical analyses. The team is breaking ground in this area as well as in the arena of genomic research. A recent publication in the journal Bioinformatics details and compares the next generation sequencing applications within the field of genetic analysis, providing best practices information for researchers around the world.
The center’s novel, multidisciplinary approach is attracting award-winning young researchers who are furthering the epigenetic research into osteoporosis, including Jigang Zhang, recipient of a 2011 American Society of Human Genetics Trainee Research Semifinalist Award and Fei-Yan Deng, Hongbin Liu, and Xiaojing Xu, all recipients of the 2011 American Society for Bone and Mineral ResearchYoung Investigator Travel Grant.
Louisiana Osteoporosis Study
The flagship project for the center focuses on the epigenetics of osteoporosis, a condition in which the loss of bone density puts people at risk for fractured and broken bones. Current research shows that the risk for osteoporosis is not fully understood, although bone density can both be inherited and altered by lifestyle choices and events.
In Louisiana, Hong Wen Deng and his team are collecting information from eligible adults as part of the Louisiana Osteoporosis Study. Participants in the 10-year study receive bone density testing and results at no charge, provide a small blood sample, and also are asked about their overall health and lifestyle. The data will be stored and available for additional research in future years.
Participants are drawn from the local New Orleans area, as well as in the Baton Rouge area, where the center has a study site located in a medical office building affiliated with Baton Rouge General Hospital. The Louisiana study builds on Deng’s previous research in both Kansas City and in Omaha. Deng intends for his sample collection to become the largest osteoporosis sample in the world.
“We focus on human studies instead of cell and animal based,” says Shen, although, he adds that there is a section looking at the cellular level to study the function of specific genes. “We focus on the human population part. We collect samples and information from the general human population, including bone mineral density information and in addition to that we have to collect a variety of different lifestyle and demographic data from the subjects, smoking, alcohol, drinking, lifestyle, and peripheral blood sample. Using those blood samples, we can collect DNA and RNA protein and sometimes cells for all those subsequent analyses.
“We can try to compare whether different groups of people have high or low bone mineral density, high risk or low risk of osteoporosis fracture, to compare whether they have different genetic polymorphism,” explains Shen. “We are just trying to see what kind of biological mechanism contributed to the differential risk of osteoporosis.” Polymorphism refers to genetic variations in a particular DNA sequence.
Even though the research project will continue over the course of the coming decade, the team publishes regularly about the study as it is in progress. Peer-reviewed publications have appeared in the Journal of Cellular Physiology, PLoS One, the Journal of Bone Mineral Metabolism, and Human Genetics. The research ranges widely, from a detailed analysis of genetic makeup to the impact of vitamin D and health history factors such as age of menarche.
However, cautions Shen, “We have a long way to go before we can apply our findings to clinical settings, to predict whether subjects will have high risk of osteoporosis or how they will respond to osteoporosis treatment based on his or her genetic information. The major outcome is to find that new genes or new factors that contribute to the bone metabolism. By finding those new mechanisms, we can try to combine them to view the biomarkers for predicting osteoporosis risk.”
This information could ultimately lead to new targets for drug development and disease prevention, says Shen.
Expanding Research Avenues
Periodontal disease is a growing area of focus of the center, says Shen, emphasizing that they are one of the first to consider the disease from an epigenetic focus. Their research could help individuals and physicians better understand why one family member struggles with periodontal disease and others in the same household – eating the same foods, drinking the same beverages, performing basically the same hygiene tasks – seem immune.
“We are the first group doing a comprehensive search for genetic factors in periodontal disease. Previously people have looked at immune factors and one or two genes, but not this big picture,” he says.
Other avenues of research center investigators are pursuing include aspects of obesity, alcoholism, leukemia, osteoarthritis, and muscle formation.
Photos by Rick Olivier