Developmental neurotoxicity and autism spectrum disorder

项目摘要 新兴全球领袖奖（K43）旨在推动职业发展和研究活动 Omamuyovwi Ijomone博士，阿库雷联邦技术大学的高级讲师/研究员， 尼日利亚。Ijomone博士的总体研究目标是提供新的信息，以了解 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影响的， 遗传和环境因素的相互作用在发育的关键阶段触发神经元死亡。 神经发育障碍是由异常的大脑发育引起的不同病症。自闭症 谱系障碍（ASD）以及其它病症福尔斯这一类。这些疾病的病因是 尚未完全理解;然而，它涉及基因-环境相互作用。环境过度污染 重金属，特别是镍（Ni）和锰（Mn），与ASD发病机制有关。期间 Ijomone博士的研究将率先使用创新的秀丽隐杆线虫模型， 尼日利亚生物医学研究界，调查ASD风险基因NRXN和NLGN的作用， 形态，行为和分子的变化所造成的发展镍和锰曝光。他 研究方法将建立在基因表达和遗传分析方法工具包的基础上，具体而言： 1)研究NRXN和NLGN在镍和锰暴露的神经发育缺陷中的作用;以及2） 阐明镍和锰暴露后神经发育缺陷的分子机制， NRXN和NLGN突变。Ijomone博士对该项目的职业发展目标是：1）建立在 现有的，并获得新的知识和技能，以有效地设计和测试假设驱动 翻译研究的想法; 2）提高granitarian和手稿写作技巧，以及提高 向决策者和公众有效传播科学研究结果的技能;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。伊城根博士将负责 该计划在Michael Aschner教授（美国导师），Ganiyu Oboh教授 （尼日利亚导师）和赫伯特拉赫曼教授（共同导师，美国）。Aschner教授是一位 神经毒理学家，对CNS发育过程中的遗传和环境相互作用感兴趣 和衰老。Oboh教授是尼日利亚顶级研究人员，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基础。Janis Weeks教授（美国），教授 在使用C. elegans模式的翻译研究将提供 额外的指导。Ijomone博士将在结构化研究和培训计划中使用K43奖， 使他能够发展成为一个完全独立的调查员和科学领导者。 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