Research Center for Molecular Pathogenesis of Schizophrenia

约翰霍普金斯大学精神分裂症研究中心的总体目标是进行跨学科研究，以了解精神分裂症的分子病理学。精神分裂症研究中最令人兴奋的进展之一是从人类基因关联研究中识别疾病易感基因。对每个易感因子的功能研究表明，这些因子不是相互独立发挥作用，而是在几条可能有助于疾病病理的共同“途径”中协同作用。越来越多的证据也强化了一种新兴的观点，即精神分裂症是一种成年发病的神经元发育状况。精神分裂症有多具体 然而，调节神经元发育的不同方面的易感因素或途径在很大程度上是未知的。我们的合作团队从我们的初步研究中获得了令人信服的证据，表明DISC1作为适配器与其他易感因素相互作用，并参与神经发育的不同阶段。因此，我们假设DISC1是一个有希望的线索，我们可以用它来探索与神经发育相关的精神分裂症病理的潜在疾病“途径”。在本研究小组和其他人收集的初步数据的基础上，我们假设神经发育的三个方面作为研究和阐明病理的重要基础。这些措施包括：(1) 这些研究包括：(1)发育中大脑皮层的突触形成；(2)发育中大脑皮层的中心体组织；(3)海马区的神经发生，将在每个项目中分别研究(项目1-3)。核心A将提供管理和总体科学指导。核心B将描述 正在研究的小鼠的行为表型/内表型作为三个项目中分子细胞生物学的模型。核心C将进行基因研究，探索最初来自生物学研究的目标可能的遗传变异，然后在每个项目中进行研究。最终目的是阐明疾病的途径，以便更好地了解疾病，为机械研究和未来的治疗策略建立适当的模型，并最终找到治疗这种疾病的新方法。

The overall goal of this Schizophrenia Research Center at Johns Hopkins is to conduct interdisciplinary studies towards understanding the molecular pathology of schizophrenia. One of the recent exciting developments in schizophrenia research is the identification of disease susceptibility genes from human genetic association studies. Functional studies of each susceptibility factor have suggested that, instead of functioning independently from each other, these factors act synergistically in several common "pathways" that may contribute to the disease pathology. Accumulating evidence also reinforces the emerging view that schizophrenia is a condition of neuronal development with an adult onset. How specific schizophrenia susceptibility factors, or pathways, regulate different aspects of neuronal development, however, is largely unknown. Our collaborative team has obtained compelling evidence from our preliminary studies that DISC1 interacts with other susceptibility factors as an adaptor and is involved in various phases of neurodevelopment. Thus, we hypothesize that DISC1 is a promising lead with which we can explore the disease "pathways" underlying the pathology of schizophrenia associated with neurodevelopment. On the basis of preliminary data that our group and others have collected, we hypothesize three aspects of neurodevelopment as an important foundation for studying and elucidating the pathology. These include: (1) synaptic formation in the developing cerebral cortex; (2) centrosomal organization in the developing cerebral cortex; and (3) neurogenesis in the hippocampus, which will be studied in each project (Projects 1-3), respectively. Core A will provide administration and overall scientific direction. Core B will characterize behavioral phenotypes/endophenotypes of mice under study as models for the molecular cellular biology in the three projects. Core C will conduct genetic studies exploring possible genetic variations in the targets originally from biological studies, which, in turn, will be studied in each project. The ultimate goal is to elucidate the disease "pathways" to have better understanding of the disease, build appropriate models for mechanistic studies and future therapeutic strategies, and eventually to identify novel ways to treat the disease.