Research

Focusing on adult hippocampal neurogenesis, we have investigated the molecular mechanisms of primary cilia in neural stem cells Amador-Arhona et al., 2011. We investigated the mechanism of SOX2 function in peripheral neurogenesis Cimadamore et al., 2011. and identified a novel epigenetic mechanism of Sox2 control over neural stem cell proliferation through the regulation of the Lin28/let7 pathway Cimadamore et al., 2013. We discovered an unsuspected role of Sox2 in priming the epigenetic landscape of the proneural gene and orchestrating a complex network, assuring proper neuronal maturation and function Amador-Arjona et al., 2015. Our studies provide a foundation for the molecular mechanisms underpinning the self-renewal and differentiation of neural stem cells using the mouse model of adult hippocampal neurogenesis and human ESC and iPSC models relevant to therapeutic applications.

We became interested in the Zika virus (ZIKV), which infects neural stem and progenitor cells. We developed a physiological model of ZIKV transmission in immunocompetent SJL mice and demonstrated that common anti-malaria drug chloroquine inhibits ZIKV propagation in SJL mouse model Shiryaev et al., 2017a. We have identified a potent inhibitor of ZIKV NS2B-NS3 protease and showed its efficacy in SJL mice Shiryaev et al., 2017b. We discovered that ZIKV protease could bind single-stranded, suggesting it has a novel function, and proposed a “reverse inchworm” model for a tightly intertwined NS2B-NS3 helicase-protease machinery Shiryaev et al., 2023. This model suggests that NS2B-NS3pro cycles between open and super-open conformations bind and release RNA, thus enabling a full-range NS3hel processivity.

We discovered that patterns of epigenetic marks in the nucleus can identify cellular states and developed a novel technique: microscopic imaging of epigenetic landscapes (MIEL). This technique captures the nuclear staining patterns of epigenetic marks and employs machine learning to accurately distinguish between such patterns Farhy et al., 2019. When applied to primary cells from organisms of different ages, we discovered that image-based chromatin and epigenetic age (ImAge) captures intrinsic age-related progressions (trajectories) of the spatial organization of chromatin and epigenetic marks in single nuclei. Such trajectories readily emerge as principal changes in each individual dataset. We propose that ImAge represents the first-in-class imaging-based biomarker of aging with single-cell resolution Alvarez-Kuglen et al., 2024 Nature Ageing in Press.

Complete List of Published Work:   https://www.ncbi.nlm.nih.gov/pubmed/?term=Terskikh+A

Alexey Terskikh, PhD