Zhiquan Li

Zhiquan Li


My PhD project contained three topics: Unrepaired DNA damage or replication stress induces PARP1 activation (Focus 1), depletes NAD+ and causes mitochondrial dysfunction and defective mitophagy (Focus 2). Both genomic instability and mitochondrial dysfunction are hallmarks of aging, in which FOXO play crucial roles by transcriptional regulation (Focus 3).

Focus 1: dNTPs play critical roles in proper cell functioning. But the molecular mechanism behind its supply in DNA damage is poorly understood. So, we propose that there’s a dNTP supply complex (DSC) which facilitates the DNA repair at the local DNA damage sites in human. We found that Tip60 and p53R2 (small subunit of RNR) can be induced by UVB irradiation and that SHMT1 and Tip60 could be recruited to the DNA damage sites upon laser irradiation. To further identify other DSC components, pull-down experiments were employed and showed the SHMT1 - SKAP2 interaction and SHMT2 - Rev1 interaction.

Focus 2: Alzheimer’s disease (AD) is the most serious dementia. Currently, nearly no treatments and early stage diagnosis are available. To further investigate the molecular mechanisms behind, we hypothesize that the potential involvement of PINK1/Parkin-independent mitophagy pathways might lead to the AD pathogenesis. So, we are investigating it in AD skin fibroblasts now.

Focus 3: FOXOs are master regulators in aging and longevity by transcribing the genes involved in DNA damage response and autophagy. However, the transcriptional targets are still unclear. To identify novel FOXO targets, transcriptomics was used and some novel targets have been discovered in silkworm. Further investigation is ongoing using fruit fly.

ID: 172788123