Active Research

암세포에서는 세포핵 크기와 형태 항상성 교란이 빈번하다. 또한 핵막의 일시적 파열과 복구가 반복되는 것으로 추정된다. 우리 실험실은 암세포 핵막 이상 및 복구의 기전과, 핵막 불안정성이 암 발달에 미치는 영향을 연구한다. 그리고 핵막 불안정성이라는 특성에 기반한 합성치사 항암제 후보를 탐색한다. 

Morphological abnormalities and membrane instability of the nuclear envelope in cancer/senescent cells

The nuclear envelope plays a key role in maintaining genome stability. DNA wrapped around histones cannot escape through the nuclear pores into the cytoplasm. However, when DNA is exposed to the cytoplasm due to temporary rupture of the nuclear envelope during interphase, DNA damage and innate immune responses are induced. Unlike normal cells, in cancer cells as well as in senescent cells, the morphological homeostasis of the nucleus is disturbed, and the frequency of nuclear envelope rupture is high. We explore molecular systems that maintain nuclear morphology and membrane stability. In addition, we are conducting research on the causes and effects of disturbed nuclear envelope integrity in cancer/senescent cells.

Transcription regulators inducing anticancer drug resistance

The transition of transcription programs is an important mechanism by which cancer cells acquire anticancer drug resistance. Cancer cells change the expression of genes that control the cytoskeletal system in response to anticancer agents that target the MAP kinase pathway. The cytoskeletal rearrangement induces a transcription program that inhibits apoptosis and induces proliferation through the activation of YAP, a Hippo signaling effector. The transcription program centered on YAP is also involved in resistance to immune-checkpoint inhibitors. We explore how to stop transcriptional programs associated with anticancer drug resistance by inhibiting YAP or other transcription regulators.