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.