Developmental neurotoxicity and autism spectrum disorder

项目总结 新兴全球领袖奖(K43)旨在推动职业发展和研究活动 阿库尔联邦技术大学高级讲师/研究员Omamuyovwi Ijomone博士， 尼日利亚。Ijomone博士的总体研究目标是为理解 神经元变性的机制。特别是，他的目标是了解大脑是如何受到 在发育的关键阶段触发神经元死亡的遗传和环境因素的相互作用。 神经发育障碍是由大脑发育异常引起的各种疾病。孤独症 除其他疾病外，谱系障碍(ASD)就属于这一类。这些疾病的病因是 尚未完全了解；然而，它涉及到基因和环境的相互作用。环境过度暴露于 重金属，特别是镍和锰，与ASD的发病机制有关。在.期间 在这个项目中，Ijomone博士的研究将开创创新的秀丽线虫模型在 尼日利亚生物医学研究界，为了调查ASD风险基因NRXN和NLGN的作用， 由发育中的镍和锰暴露引起的形态、行为和分子变化。他的 研究方法将建立在基因表达和遗传分析方法学工具包的基础上，具体如下： 1)研究NRXN和NLGN在镍、锰暴露的神经发育缺陷中的作用； 镍、锰暴露致小鼠神经发育缺陷的分子机制 NRXN和NLGN突变。Ijomone博士这个项目的职业发展目标是：1)在 现有并获得新的知识和技能以有效地设计和测试假设驱动 翻译研究思路；2)提高翻译技巧和稿件写作技巧，以及改进 向政策制定者和公众有效传播科学发现的技能；以及3) 为尼日利亚的科学平台做出贡献，并建设当地的研究能力。Ijomone博士将承诺 该项目由Michael Aschner教授(美国导师)、Ganiyu Oboh教授合作指导 和赫伯特·拉赫曼教授(共同导师，美国)。阿施纳教授是一位领先的 神经毒理学家，研究中枢神经系统发育过程中遗传和环境的相互作用 和衰老。Oboh教授是尼日利亚的顶级研究人员，其专业知识包括毒理学和 神经保护。拉赫曼教授是内科医生和行为遗传学家，对分子和 包括ASD在内的神经发育障碍的遗传学基础。贾尼斯·威克斯教授(美国)，教授 在使用线虫模型进行翻译研究方面拥有丰富经验的Emerita将提供 其他指导意见。Ijomone博士将在一个结构化的研究和培训计划中使用K43奖来 使他能够发展成为一名完全独立的调查员和科学领先者。 1

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