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 previous work we showed that in our cohort of 100 kidney transplant recipients, over half (56%) gained weight with the average amount of 9 kg. within the first year following transplantation, 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 use emerging omic technologies/methodologies to (1) identify environmental factors associated with post-transplant weight gain, (2) identify gene expressions associated with weight gain, (3) use emerging analysis methodologies to determine combinations of gene- environment interactions that predict weight gain and obesity. Originally 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 the impact of plasma brain-derived neurotrophic factor (BDNF) concentration on weight gain after kidney transplantation and we are in the process of publishing on the characterization of exosomal protein profiles and their impact on weight changes after kidney transplantation. Publications related to emerging methods in other populations included a publication on the microbiome in patients with severe aplastic anemia. Other publications included commentaries on using genomics and other omic techniques to explore nursing research questions relevant to symptom science. This year my NIH lab will be closing. However, I will continue collaborative work with other NIH projects.
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