Most symptoms are multifactorial in origin with both genetic and environmental factors contributing to individual variations. Candidate gene studies on the basis of biological hypotheses have been performed to identify relevant genetic variation in complex traits such as pain. However, the complicated mesh of contributing factors and the thousands of molecules involved in different symptoms makes it difficult to detect responsible genetic variations for an individuals unique susceptibility to disorders. It is unlikely that common variations in a single gene act dominantly on complex traits;rather, the contribution of each gene seems to be subtle, acting on one of multiple biological pathways, making its signal difficult to detect. The combined impact of the rapid increase in knowledge of diseases and the ability to apply powerful and high capacity technology has raised expectations for more effective and safer medicines for various types of symptoms management. Developing new treatment strategies for symptoms management is also critically dependent on identifying new target molecules and defining phenotypes for specific types of disorders. Therefore the first step of this project has been to define the characteristics of experimental and clinical phenotypes. Recently, we launched multiple projects with next generation sequencing (NGS) technology, which allows us to perform entire and/or targeted genome sequencing. The role of genetic and epigenetic factors on symptoms in various disorders and/or conditions will continue to be studied. For example, in neurological disorders such as acute pain, mild traumatic brain injury and PTSD, we are using genotyping, gene and protein expression, and patient reported outcomes to better understand the reciprocal interplay between these factors and the numerous biologic/mechanistic pathways including the inflammatory cascade. Gene expression profiles from the soldiers back from war zone were presented at the multiple meetings (CNRM and ASN meeting) and have been submitted for publication. Two epigenetic studies using DNA methylation chromatin immunoprecipitation followed by whole genome scale sequencing were conducted from civilian and military groups. Epigenetic changes in the sports related concussion patients will be presented at the ASHG meeting. The second epigenetic study in military PTSD patients finished sequencing of samples and the data are under the analysis. Using the targeted next generation sequencing technology, we also have 2 on-going microbiome projects to characterize population of microorganisms in human and/or animal body from different disease status. Using a next generation semiconductor sequencer, microbiome was analyzed with extensive sequencing of 16s rRNA region in an animal model of irritable bowel syndrome and human patients. The results were presented at the scientific meeting and submitted for publication. Another microbiome project was launched recently for oral microbiome from the aplastic anemia patients. So far, preliminary data analysis was finished and its result will be presented at the IADR meeting. Additional samples will be sequenced and analyzed. Mainly both projects found that the microbiome composition is altered in specific disease conditions. Developing new analyzing methods for the high throughput big data generated by the next generation sequencers is another goal of these projects. From these results along with biological knowledge of multiple pathways in neurological disorders, we will be able to suggest molecular-genetic mechanisms of those diseases at the level of the individual. Finally, we can suggest integrative genomic analysis to develop new drugs and test them based on individual genetic information.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
National Institute of Nursing Research
Department
Type
DUNS #
City
State
Country
Zip Code
Gill, Jessica; Cashion, Ann; Osier, Nicole et al. (2017) Moderate blast exposure alters gene expression and levels of amyloid precursor protein. Neurol Genet 3:e186
Martin, Christiana G; Kim, Hyungsuk; Yun, Sijung et al. (2017) Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans. Psychiatry Res 251:261-265
Lee, Hyunhwa; Gill, Jessica; Barr, Taura et al. (2017) Primer in Genetics and Genomics, Article 2-Advancing Nursing Research With Genomic Approaches. Biol Res Nurs 19:229-239
Lejbman, Natasha; Olivera, Anlys; Heinzelmann, Morgan et al. (2016) Active duty service members who sustain a traumatic brain injury have chronically elevated peripheral concentrations of A?40 and lower ratios of A?42/40. Brain Inj 30:1436-1441
Barb, Jennifer J; Oler, Andrew J; Kim, Hyung-Suk et al. (2016) Development of an Analysis Pipeline Characterizing Multiple Hypervariable Regions of 16S rRNA Using Mock Samples. PLoS One 11:e0148047
Cho, Young-Eun; Latour, Lawrence L; Kim, Hyungsuk et al. (2016) Older Age Results in Differential Gene Expression after Mild Traumatic Brain Injury and Is Linked to Imaging Differences at Acute Follow-up. Front Aging Neurosci 8:168
Cho, Young-Eun; Kim, Hyung-Suk; Lai, Chen et al. (2016) Oxidative stress is associated with weight gain in recipients at 12-months following kidney transplantation. Clin Biochem 49:237-42
Logan, Jeongok G; Engler, Mary B; Kim, Hyungsuk (2015) Genetic determinants of arterial stiffness. J Cardiovasc Transl Res 8:23-43
Roy, Michael J; Costanzo, Michelle; Gill, Jessica et al. (2015) Predictors of Neurocognitive Syndromes in Combat Veterans. Cureus 7:e293
Gill, Jessica M; Lee, Hyunhwa; Baxter, Tristin et al. (2015) A Diagnosis of Insomnia Is Associated With Differential Expression of Sleep-Regulating Genes in Military Personnel. Biol Res Nurs 17:384-92

Showing the most recent 10 out of 17 publications