NO. 44

CIMR Wednesday Lecture Series

Time:

Wednesday, Oct. 23 2024, 4:00 p.m.

Location:

Yifu Lecture Hall, North Basic Research Building 

Host：

Kaibin Shi  (史凯斌)

Chinese Institutes for Medical Research

Speaker：

Zhi-Qi Xiong (熊志奇)

Senior investigator

Institute of Neuroscience

Chinese Academy of Sciences

TITLE：

Neurobiology of Disease: Collaborations between Neurologist and Scientist

ABSTRACT:

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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