Project summary The Emerging Global Leader Award (K43) aims to advance the career development and research activities of Dr. Omamuyovwi Ijomone, a Senior Lecturer/Researcher at the Federal University of Technology, Akure, Nigeria. Dr. Ijomone’s overall research goal is to contribute novel information to understanding the mechanisms of neuronal degeneration. Particularly, he aims to understand how the brain is affected by an interplay of genetic and environmental factors that trigger neuronal death at critical stages of development. Neurodevelopmental disorders are diverse conditions resulting from aberrant brain development. Autism spectrum disorder (ASD), amongst other conditions, falls in this category. The etiology of these diseases is not fully understood; however, it involves gene-environmental interplay. Environmental overexposure to heavy metals, specifically nickel (Ni) and manganese (Mn), have been linked to ASD pathogenesis. During this program, Dr. Ijomone’s research will pioneer the use of the innovative Caenorhabditis elegans model in the Nigerian biomedical research community, to investigate the role of ASD risk genes, NRXN and NLGN, in morphological, behavioral, and molecular alterations caused by developmental Ni and Mn exposures. His research approach will build on gene expression and genetic analysis methodological toolkit to specifically: 1) investigate the role of NRXN and NLGN in neurodevelopmental deficits of Ni and Mn exposures; and 2) elucidate molecular mechanisms underlying neurodevelopmental deficits of Ni and Mn exposures upon NRXN and NLGN mutations. Dr. Ijomone’s career development goals for this program are to: 1) build on existing, and acquire new knowledge and skills to effectively design and tests hypothesis-driven translational research ideas; 2) improve grantsmanship and manuscript writing skills, as well as improve skills for effective communication of scientific findings to policymakers and the general public; and 3) contribute to the scientific platform in Nigeria and build local research capacity. Dr. Ijomone will undertake this program under the collaborative mentorship of Prof. Michael Aschner (USA mentor), Prof. Ganiyu Oboh (Nigeria mentor), and Prof. Herbert Lachman (Co-mentor, USA). Prof. Aschner is a leading neurotoxicologist with research interest in genetic and environmental interplay during CNS development and senescence. Prof. Oboh is a top Nigerian researcher with expertise that include toxicology and neuroprotection. Prof. Lachman is physician and behavioral geneticist interested in the molecular and genetic basis of neurodevelopmental disorders including ASD. Prof. Janis Weeks (USA), a Professor Emerita with extensive experience in using the C. elegans model for translational research will provide additional guidance. Dr. Ijomone will use the K43 award in a structured research and training program to enable him to develop into a fully independent investigator and a scientific leader. 1

Project narrative Increasing evidence associates exposure to environment toxicants such as heavy metals to negative neurological consequences, particularly, perinatal exposure to heavy metals is increasingly linked to neurodevelopmental disorders. Our study aims to investigate morphological, behavioral, and molecular alterations caused by developmental exposure to heavy metals in relation to endpoints of autism spectrum disorders (ASD). Our proposal will provide novel translational information on the importance of inherent genetic differences and exogenous chemical perturbations of cellular processes as potential modifiers of metal-induced neurotoxicity and neurodevelopmental disorders such as ASD; thus, laying the groundwork for innovative therapeutic strategies against neurodevelopmental disorders.