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Open Access Publications from the University of California

Scholarly Works (2 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2017)

Although Chimeric Antigen Receptor (CAR) T cells have been proven to be powerful in eradicating tumors. However, its non-specific activity against normal tissues and cells has been a major problem. Here, utilizing the activation of transient receptor potential cation channel subfamily V member 1 (TRPV1) under heat, the translocation of nuclear factor of activated T-cells (NFAT) triggered by Calcium influx, and the recombination effects of Cre-lox system, we have developed a system to remotely manipulate the expression of proteins in cells under the control of both heat and drugs. The significance of this project is to provide a method to precisely control the activities of CAR T cells within targeted local tissues.

    Cover page: Dynamic Genetic Control: Manipulating Cell Behaviors Using Heat
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2018)
    The dramatic reorganization of chromatin during mitosis is perhaps one of the most fundamental of all cell processes. It remains unclear how epigenetic histone modifications, despite their crucial roles in regulating chromatin architectures, are dynamically coordinated with chromatin reorganization in controlling this process. We have developed and characterized biosensors with high sensitivity and specificity based on fluorescence resonance energy transfer (FRET). These biosensors were incorporated into nucleosomes to visualize histone H3 Lys-9 trimethylation (H3K9me3) and histone H3 Ser-10 phosphorylation (H3S10p) simultaneously in the same live cell. We observed an anticorrelated coupling in time between H3K9me3 and H3S10p in a single live cell during mitosis. A transient increase of H3S10p during mitosis is accompanied by a decrease of H3K9me3 that recovers before the restoration of H3S10p upon mitotic exit. We further showed that H3S10p is causatively critical for the decrease of H3K9me3 and the consequent reduction of heterochromatin structure, leading to the subsequent global chromatin reorganization and nuclear envelope dissolution as a cell enters mitosis. These results suggest a tight coupling of H3S10p and H3K9me3 dynamics in the regulation of heterochromatin dissolution before a global chromatin reorganization during mitosis.
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