医学创新论坛第44期

CIMR Wednesday Lecture Series

时间：2024年10月23日（周三）下午4:00

地点：首都医科大学基础科研楼北楼一层逸夫报告厅

主持人：史凯斌

首都医学科学创新中心

报告人：熊志奇

中国科学院神经科学研究所高级研究员

报告题目：

Neurobiology of Disease: Collaborations between Neurologist and Scientist

摘要：

Advancements in pathogenesis, diagnostics and treatment of brain diseases require a close collaboration between investigators and clinicians. In this talk, I will use brain calcification as an example to address how can a neuroscientist engage in collaborative research with neurologists.  Brain calcification is common and has negative consequences for brain function. Search for mechanisms and new ways to treat brain calcification is therefore of interest. The most common genetic cause of brain calcification is loss-of-function mutations in the SLC20A2 gene, encoding the PIT2 phosphate transporter. Heterozygous loss of function is sufficient to cause disease in human.  In collbaoration with neurologist Dr Chen Wanjin, we found extensive brain calcification is associated with homozygous and compound heterozygous mutations in the MYORG gene. Together with MYORG gene expession data allow us to conclude that the astrocyte-mediated Pi transport is pivotal for brain Pi homeostasis. Furthermore, we identified a set of intronic mutations in SLC20A2 that cause aberrant splicing into cryptic exons and truncation of the protein.  Finally, we demonstrated that ASO-mediated targeting of the cryptic splice site may work to treat patients with decreased PIT2 levels, regardless of the type of mutation causing the disease.

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