The candidate is focused on building a research career in HIV symptom management and the development of a biomarker for the objective assessment of fatigue. In the PhD, he was able to identify predictors and correlates of fatigue and depression in men and women with HIV/AIDS, and found significant relationships between environmental, personal, and symptom variables. Fifty-four percent of the total variance in quality of life were explained by these three concepts. The strongest predictors were symptoms such as fatigue (34% of the variance), lipodystrophy (1.5%), neuropathy (1.0%), depression (1.3%), and shortness of breath (2.5%). These symptoms occur in clusters, which clearly points to mechanisms of mitochondrial intoxication and energy loss. In his postdoctorate, he wants to receive additional training in molecular biology and genetics to develop a biomarker for fatigue. The purpose of his studies will be to understand the relationship between nucleoside analog treatment in HIV/AIDS and mitochondrial intoxication in human muscle cells. The results of his research will broaden the understanding of the mechanisms underlying mitochondrial function and replication, and may lead to the development of a biomarker for fatigue. An objective fatigue measure in HIV/AIDS is much needed, in order to monitor patients for increasing reports of complications such as lactic acidosis, hepatic steatosis, and lipodystrophy. Currently fatigue is assessed subjectively, which may or may not reflect the physiological changes that are ongoing in people with HIV/AIDS. As continuation of his scientific development, the postdoctorate is a next step for a promising future as a nurse researcher who is able to investigate basic science phenomena and translate them back into interventional research that is relevant to patients and their families, and to the clinicians. Dr. Dallakas has been selected as mentor due to his expertise in muscular diseases and his accomplishments in the identification of mitochondrial intoxication in men and women with HIV, evident by his extensive publication record. The environment of Dr. Dalakas' laboratory is promoting the training and development of expertise that is necessary for the applicant's scientific growth. Dr. Dalakas is daily available for consultations either in person and meets informally with everyone daily in the laboratory to discuss the progress and problems of ongoing research projects. Space requirements and equipment are available for the applicant's use in pursuing his research. Additionally, there are senior researchers and a research assistant to support the applicant's needs. The study examines the role of genetic and molecular changes in mitochondria in healthy and HIV-infected myocyte cultures that will be exposed to NRTIs to identify a biomarker for mitochondrial function vs. dysfunction. A variety of molecular and genetic approaches will be utilized to test this hypothesis. The goal of this project is to identify a biomarker to detect toxic changes in the mitochondria, and to develop a reliable marker for fatigue, thus leading to new strategies in clinical evaluation, outcomes research, and fatigue prevention methods. ? ?
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