Solomon Oforoi – Acquah

Dean of the School of Biomedical and Allied Health Sciences in the University of Ghana

Solomon Oforoi – Acquah

Dean of the School of Biomedical and Allied Health Sciences in the University of Ghana
sofori-acquah@ug.edu.gh

Biography

Prof. Solomon Oforoi – Acquah
Dean of the School of Biomedical and Allied Health Sciences in the University of Ghana
Email: sofori-acquah@ug.edu.gh

Professor Ofori-Acquah was appointed Dean of the School of Biomedical and Allied Health Sciences in the University of Ghana in January 2017. He is Principal Investigator of the Sickle Cell Disease Genomics Network of Africa (SickleGenAfrica). He holds a joint appointment in the University of Pittsburgh, USA as Associate Professor of Medicine and Human Genetics. He is Director of the Center for Translational and International Hematology at the University of Pittsburgh. Professor Ofori-Acquah was born in Cape Coast and attended Adisadel College from 1977-1984 where he was the Sargent Major of the College Cadet Corps. He migrated to England in 1985 to pursue higher education initially in Medical Laboratory Sciences obtaining a Higher National Certificate in Hematology and Blood Transfusion in 1989 and Part 1 Fellowship of the Institute of Biomedical Sciences in 1990. Further studies resulted in MSc in Bio-molecular Organization from Birkbeck College, University of London in 1992, and PhD in Molecular Genetics from the University of London (King’s College London) in 2000. His Postdoctoral studies in the University of South Alabama, USA focused on therapeutic applications of missense RNA in sickle cell disease (SCD). He was appointed Scholar of the Comprehensive Sickle Cell Center in 2001, and Assistant Professor of Cell Biology and Neuroscience in 2002 at the University of South Alabama. He joined Emory University as Assistant Professor of Pediatrics in 2007 and the University of Pittsburgh in 2013 as Tenured Associate Professor of Medicine.

Professor Ofori-Acquah’s research is focused on molecular and cellular pathogenesis of SCD. His seminal publication in the Journal of Clinical Investigation in 2013 was the first to define free heme as a prototypical danger molecule in SCD and provided the field with the first mouse model of the Acute Chest Syndrome. He maintains two research programs focused largely on transgenic mouse models in the USA, and well phenotyped patient cohorts in Ghana and Africa. His work in Africa is supported under the auspices of the Human Hereditary and Health in Africa (H3Africa) Consortium. Professor Ofori-Acquah has received multiple Research, Training and Achievement Awards. His research has continuously been funded by the NIH since 2004 totaling nearly $30 million. He has authored over 60 research papers, reviews and book chapters, and mentored over 30 Junior Scientists, Physicians and Students. He is an Expert NIH Reviewer with service on multiple Study Sections focused on Respiratory Biology, Hematology and Genomics. His service on Advisory Boards includes Chair of the Laboratory Sub-Committee of the Ghana National Technical Advisory Committee for Newborn Screening in 2011-2013. Professor Ofori-Acquah is a Founding Executive Member of the Ghana Biomedical Convention and served as Inaugural Chair of the Scientific Committee in 2008. He was Vice-President and President of the Convention in 2012 and 2013 respectively. In 2016 he received an Appreciation Award for his role in founding the Ghana Biomedical Convention.

Genetic and epigenetic modulation of the acute chest syndrome in sickle cell disease. Solomon F. Ofori – Acquah. School of Biomedical and Allied Health Sciences, University of Ghana, Korle Bu, Accra, Ghana. Center for Translational and International Hematology, Vascular Medicine Institute, University of Pittsburgh, PA, USA.

Acute respiratory distress syndrome in sickle cell disease (SCD) is referred to as acute chest syndrome (ACS). It is the leading cause of intensive care admissions and premature death in SCD. While multiple etiological factors are involved in ACS our group has focused on the role and mechanism of hemolysis and its prototypical danger associated molecular pattern molecule, extracellular heme in the pathobiology of ACS. We discovered that infusion of a modest amount of extracellular heme caused biologic, physiologic and clinical features of ACS exclusively in transgenic homozygous SCD (SS) mice but not in littermates with sickle cell trait thus establishing a lethal mouse model of ACS (Ghosh et al., J Clin Invest, 2013). Heme oxygenase-1 (HO-1) is the inducible rate-limiting heme degradation enzyme. Our studies indicate that the heme/HO-1 axis influences the risk and prognosis of ACS. Genetic association studies of a large cohort of children identified variants of (GT)n in the promoter of the HO-1 gene (HMOX1) to be linked to rates of hospitalization for ACS. A subsequent independent study identified one SNP in the 3′ untranslated region of HMOX1 to be associated with ACS at low significance (rs12160039; P = .02), and a second SNP (rs6141803) located 8.2 kilobases upstream of COMMD7 at higher significance (P = 4.1 × 10−7). The COMMD7 protein interacts with nuclear factor-κB signaling to modulate inflammation. Earlier global transcriptional profiling studies by our group demonstrated that extracellular heme significantly alters the expression COMMD7 in endothelium thus providing a functional pathophysiological link between rs6141803 and ACS. We have followed up these studies with NGS sequencing of genes in the HMOX1 pathway to identify likely targets of action involved in ACS pathobiology. A major unresolved issue is why ACS is more frequently diagnosed in children yet the mortality rate is 10-fold higher in adults. In more recent studies, we discovered that acute elevation of extracellular heme caused acute intravascular hemolysis in both young (4-6 weeks old) and adult (>12 weeks old) SS mice. While all the adult mice succumbed to ACS as we have previously reported (Ghosh et al., J Clin Invest, 2013) nearly all the young mice survived (n=18/20 each; p<0.0001). The young SS mice rapidly cleared heme from the circulation by a novel mechanism independent of hemopexin the primary plasma heme scavenger. Further studies identified HO-1 as a putative candidate since the concentration of this enzyme in the plasma of the young SS mice was markedly raised (p=<0.001). To assess clinical relevance we studied two large pediatric and adult patient cohorts and confirmed that HO-1 activity in blood is significantly higher in children than in adults with SCD. We have found that a highly conserved CpG island in the proximal HMOX1 promoter is methylated in peripheral blood mononuclear cells of old but not of young SS mice. This differential DNA methylation may explain the progressive decline of HO-1 activity with aging in SCD. Experiments using pharmacologic gain-of-function and loss-of-function tools in SS mice confirm that HO-1 activity controls age-related mortality in ACS. These experiments allow us to confer protection to adult SS mice from inevitable heme-induced ACS lethality by augmenting HO-1 activity, and to remove protection in young SS mice by inhibiting HO-1 activity. We have generated SS mice with conditional knock-out of HMOX1 in blood cells to locate the cellular origin of HO-1 that ameliorates ACS. Our studies allow us to propose HO-1 as a genetic and epigenetic modulator of ACS and thus an attractive therapeutic target in SCD.