Project description:‘Big tau’, a longer isoform of tau is expressed in peripheral nervous system (PNS) and specific regions of the central nervous system (CNS). Big tau distribution across the human nervous system and pathophysiological role remains largely unknown. Here, using mass spectrometry, we demonstrate the big tau protein results from the insertion of exon 4a-long in the human MAPT sequence. We observed a central-to-peripheral gradient of big tau expression, lowest in the cortical brain region, followed by the cerebellum, then spinal cord, with the highest level in the human sciatic nerve (PNS). Interestingly, brain regions overlapping with relatively lower big tau are more susceptible to neurofibrillary tangle (NFT) formation. Furthermore, we found that CSF big tau levels did not change with CSF Aβ abnormalities in AD, unlike the CNS tau isoform, which increased significantly with concomitant Aβ and cognitive abnormalities. Our findings provide new insights into the basic biology of big tau in humans, crucial for understanding its pathophysiological functions.
Project description:The results of the study uncover conserved features of cancer methylomes and provide a mechanistic explanation for the tumor-promoting effects of Dnmt3a mutations. Whole genome methylation analysis of Mus musculus. Five samples were analyzed, one control sample containing normal healthy lung tissue, two samples containing big (WTB) or small (WTS) Dnmt3a WT tumors, two samples containing big (KOB) or small (KOS) Dnmt3a knock-out tumors
Project description:The next generation of personalized medical treatment according to the type of personal genetic information are evolving rapidly. The genome analysis needs systematic infra and database based on personal genetic information. Therefore, a big data of genome-clinical information is important.
To determine the feasibility of the use of tumor’s molecular profiling and targeted therapies in the treatment of advanced cancer and to determine the clinical outcome(Response rate,PFS, duration of response and overall survival )of patients with advanced cancer, the investigators are going to take a tumor tissue of patients and process molecular profiling and receive molecular profile directed treatments.