# Zhixun Dou Assistant Professor ![Dou](/sites/g/files/omnuum5321/files/styles/hwp_4_5__480x600/public/2024-10/Untitled_1.jpg?itok=SJkEX-WI) smartphone [617-643-0580](tel:617-643-0580) email Massachusetts General Hospital Simches Research Center CPZN 4234, 185 Cambridge Street Boston, MA 02114 Our lab investigates aging and cancer with an emphasis on nuclear events. Our group discovered that the nucleus of a cell undergoes profound degeneration during aging and tumorigenesis. Our goal is to understand the mechanisms of nuclear degeneration and to develop novel strategies to intervene in chronic inflammation associated with aging and cancer. Research topics in the laboratory include cellular senescence, inflammation, autophagy, and chromatin & epigenetics in the broad scenarios of aging and cancer. (1) The biology of cellular senescence. Cellular senescence, also referred to as the Hayflick limit, is a stable form of cell cycle arrest associated with pro-inflammatory responses. Senescence restricts proliferation of damaged cells, and hence is a tumor suppressive mechanism. However, senescent cells accumulate in aged tissues, contributing to many age-associated diseases. Our study shows that senescent cells generate chromatin fragment in the cytoplasm, which is interpreted by the cell as a “danger signal” and activates the cytosolic DNA sensing cGAS-STING pathway, leading to inflammation. We aim to understand how cytoplasmic chromatin is generated and the interaction between senescent cells and the immune system. (2) Nuclear autophagy. The nucleus is a central cellular entity. Our study suggests that nuclear components, including nuclear lamina and chromatin, can be degraded by autophagy. While autophagy is generally viewed as a cytoplasmic recycling mechanism, the degradation of nuclear materials is beginning to unravel. We are interested in unveiling novel nuclear and chromatin substrates of autophagy and the biological significance of nuclear autophagy in aging and cancer. (3) Mechanisms of mammalian aging. We are broadly interested in the biology of aging at the molecular, cellular, and organismal levels. In particular, chronic inflammation in the absence of infection contributes to most, if not all, age-associated disorders. We are interested in deciphering the mechanisms of age-associated chronic inflammation and its impact on tissue biology and disease. Our long-term goal is to develop novel approaches to treat age-related diseases and to promote healthy aging without diseases. - ## Program Affiliation [Developmental and Regenerative Biology](/bbs-faculty/developmental-and-regenerative-biology) - ## Discipline [Biochemistry](/discipline/biochemistry) [Cancer Biology](/discipline/cancer-biology) [Cell Biology](/discipline/cell-biology) [Genetics](/discipline/genetics) [Immunology](/discipline/immunology) [Molecular Biology](/discipline/molecular-biology) - ## Organism [Human](/organism/human) [Mouse](/organism/mouse) - ## People [Faculty](/people/faculty) - ## Location [Massachusetts General Hospital](/location/massachusetts-general-hospital)