Use of Peripheral Blood Mononuclear Cells Mitochondrial DNA Content to Detect Hepatocellular Carcinoma in Hepatitis B Virus Infected Nigerians.

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Project summary The research in this five-year career development application will investigate the diagnostic accuracy of mitochondrial DNA content of peripheral blood mononuclear cells (MtDNA-PBMCs) as a minimally invasive diagnostic test for detecting HBV-hepatocellular carcinoma (HCC). The applicant - Rahmat Adetutu Adisa from Nigeria - was a Fogarty Fellow in 2019 and 2020 and is currently a trainee on an NIH/FIC (D43TW010934). Her overall goal for this K43 submission is to become an independent basic translational scientist with a unique interest in interrogating the mitochondria for mechanistic purposes and as therapeutic targets for alleviating the scourge of liver cancer in Africa. To achieve her set goals, she will acquire new competencies to strengthen her current capabilities in 1) Clinical and translational research methods; 2) Molecular biology and genomics techniques in mitochondrial research; 3) Data management and statistical analyses; and 4) Scientific writing and grantsmanship. In the proposed study, she will enroll chronic hepatitis B (CHB) and HCC patients at two gastroenterology clinics in Lagos, Nigeria, and determine under AIM 1 whether PBMC mtDNA content can successfully differentiate active HBV+/HCC+ from CHB-infected patients and uninfected controls with a better diagnostic performance compared to current methods. Under Aim 2, she will determine whether PBMC mtDNA content can predict the severity of HCC in HBV-associated HCC and in CHB-infected patients. She will also investigate any associated risk factors including age, gender, alcohol intake, smoking that may predict or impact severity. In AIM 3 she will identify and evaluate the frequencies of mtDNA 4977 base pair (bp) deletions in the PBMC of HBV-associated HCC, CHB-infected, and healthy participants and provide confirmatory pieces of evidence through sequence analysis. This study AIM would be the first in Nigeria and sub-Saharan Africa.The overall public health significance of findings from this study is the small tissue samples required for analysis, the easy accessibility of peripheral blood for sampling, and the anticipated convenience and safety of PBMC mtDNA as a screening tool which can provide the impetus for policy shift to advocate for early screening of HCC using the mtDNA content. The candidate will leverage on the resources, research and capacity building trainings to be availed through this application, 75% protected time support provided by her institution, the mentorship support, experience and expertise of her team of mentors in the US, India, and Nigeria to acquire new career development skills for a successful transition to an independent basic translational researcher which is the overarching goal of this application.