Obesity, a growing epidemic in the US and a health care priority in Healthy People 2015, is a risk factor for type 2 diabetes and cardiovascular disease. In recent work we have shown that in our cohort of 100 kidney transplant recipients, over half (56%) gained weight with the average amount of 9 kg., which is significantly more than the 1 kg average weight gain in US adults. This predictable and significant weight gain within a short amount of time, and its association with morbidity and mortality, makes this a high priority concern. The focus of this research program is on discovery and utilization of biomarkers in combination with behavioral, environmental and clinical factors to predict clinical outcomes, with the long term goal to guide therapies in various patient populations. For example, obesity, a growing epidemic in the US and a health care priority in Healthy People 2015, is a risk factor for type 2 diabetes and cardiovascular disease. In recent work we have shown that in our cohort of 100 kidney transplant recipients, over half (56%) gained weight with the average amount of 9 kg., which is significantly more than the 1 kg average weight gain in US adults. This predictable and significant weight gain within a short amount of time, and its association with morbidity and mortality, makes this a high priority concern. Using the NIH-Symptom Science Model to guide us, we have conducted studies on samples prospectively obtained from kidney transplant recipients. We examined genomic, proteomic, and environmental factors (food intake, physical activity, demographic, health status, psychosocial) contributing to obesity at one year following renal transplantation in recipients. Long-term goals include prevention and treatment of obesity in recipients. Our hypothesis is that gene- environmental interactions can predict whether individuals will gain weight/become obese at one year post-transplant. Specifically we will (1) identify environmental factors associated with post-transplant weight gain, (2) identify gene expressions associated with weight gain, (3) use Bayesian analysis to determine combinations of gene- environment interactions that predict weight gain and obesity. A prospective design was used to compare genetic and environmental factors and clinical outcomes at baseline, 3, 6, and 12 months post-transplant. Gene expression profiling using microarray analysis and real-time polymerase chain reaction on adipose tissue was used to identify key regulatory elements that play a major role in obesity. Bayesian Network modeling was used to investigate causal relationships. This significant and innovative study incorporates an interdisciplinary approach to combine emerging genomic and bioinformatic technologies with traditional methodologies to explicate key gene-environment interactions responsible for post-transplant obesity. The relevance of this study is that findings will assist health care practitioners in caring for renal transplant recipients so that they do not gain weight and become obese following renal transplantation. This will result in fewer health care problems following transplantation. Our recent studies and publications have reported on findings including 1.) relationships between fruit and vegetable consumption and weight gain in kidney transplant recipients within one year post transplantation; 2.) a pilot study of demographic and dopaminergic genetic contributions to weight change in kidney transplant recipients; 3.) oxidative stress and associations with weight . Studies and publications related to biomarker discovery in other populations include 1.) sports-related concussion results in differential expression of inflammatory genes in peripheral blood during the acute and sub-acute period and 2) development of an analysis pipeline characterizing the oral microbiome in severe aplastic anemia patients. Future work will explore the ability of a signature (ie, biomarker) to further explore the underlying biologic mechanisms and to provide therapeutic guidance to monitor treatment and prevent/modify adverse outcomes.

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2
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2015
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National Institute of Nursing Research
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Cashion, Ann K; Grady, Patricia A (2018) Response to the Commentary: Precision Health: Using Omics to Optimize Self-Management of Chronic Pain in Aging: From the Perspective of the NINR Intramural Research Program. Res Gerontol Nurs 11:14-15
Martin, Christiana; Cho, Young-Eun; Kim, Hyungsuk et al. (2018) Altered DNA Methylation Patterns Associated With Clinically Relevant Increases in PTSD Symptoms and PTSD Symptom Profiles in Military Personnel. Biol Res Nurs 20:352-358
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
Pantik, Catherine; Cho, Young-Eun; Hathaway, Donna et al. (2017) Characterization of Body Composition and Fat Mass Distribution 1 Year After Kidney Transplantation. Prog Transplant 27:10-15
Gill, Jessica; Merchant-Borna, Kian; Lee, Hyunhwa et al. (2016) Sports-Related Concussion Results in Differential Expression of Nuclear Factor-?B Pathway Genes in Peripheral Blood During the Acute and Subacute Periods. J Head Trauma Rehabil 31:269-76
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
Cashion, Ann K; Gill, Jessica; Hawes, Rebecca et al. (2016) National Institutes of Health Symptom Science Model sheds light on patient symptoms. Nurs Outlook 64:499-506
Stanfill, Ansley; Hathaway, Donna; Bloodworth, Robin et al. (2016) A Prospective Study of Depression and Weight Change After Kidney Transplant. Prog Transplant 26:70-4
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

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