Abstract:
In eukaryotic cells, transcription and translation processes are physically separated by the nuclear envelope (NE). Newly transcribed mRNAs must be exported to the cytoplasm for protein synthesis, while some proteins require to be imported into the nucleus to fulfill their nuclear functions. This nucleocytoplasmic transport (NCT) across the NE is tightly regulated and is critical for maintaining cellular homeostasis. Its dysregulation leads to aging and many neurological diseases, including amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and Alzheimer’s disease (AD). To decipher the pathophysiological mechanisms underlying NCT-impaired neurological diseases, the examination of NCT activities at the single cell level is critical. Recently, we reported the techniques for measuring the nuclear transport of both mRNA and protein cargos. Fluorescent In Situ Hybridization (FISH) coupled with oligodT probes were used to measure the distribution of Poly(A) RNAs (mRNA). A dual reporter (GFP-NES and RFP-NLS) was used to examine the protein nuclear transport. The approaches together with imaging analysis enable us to systematically quantify the NCT activities in cultured neurons. We modele movement disorder dystonia using patient-derived motor neurons (MNs), which have been generated via direct conversion from patient fibroblasts and the differentiation of induced pluripotent stem cells (iPSCs). We first reported the disease dependent cellular deficits of dystonia in patient-derived neurons, including deformed nucleus, mislocalized proteins, and impaired nucleocytoplasmic transport, providing another example of the impairment of NCT in neurological diseases. Our study also demonstrates the high value of patient-derived neurons in modeling neurological diseases.
Note: The techniques for the nucleocytoplasmic transport measurement and the generation of patientderived neurons can be found in our recent publications (PMID: 35300000, 34746870, 34536661,
34380890, 33468570, 33510083, 32783653, 32317929).
Biography:
Dr. Baojin Ding received his bachelor’s degree in Medicine (MD equivalent) and master’s degree in Clinical Laboratory in China. After he received PhD in Biochemistry and Molecular Biology from Louisiana State University (LSU), he did postdoctoral training in Neuroscience at the UMass Medical School and worked as a research faculty in the UT Southwestern Medical Center. In 2018, he obtained as a  Assistant Professor (tenure-track) at the University of Louisiana at Lafayette and then relocated to Louisiana State University Health Sciences Center at Shreveport. The research at his  laboratory is
focusing on Molecular and Cellular Neuroscience and Neurological Diseases, and currently funded by NIH and DoD.

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