Dou Laboratory: Zhixun Dou, PhD

Overview

The Laboratory of Zhixun Dou, PhD, at Massachusetts General Hospital is interested in the mechanisms of mammalian aging. Aging is a chronic process associated with deteriorating physiological functions and increasing risks for multiple diseases such as cancer, cardiovascular diseases, neurodegeneration and metabolic disorders. Our goals are to develop new approaches to facilitate tissue regeneration and to intervene in diseases of aging.

Research topics in the laboratory in the broad scenarios of aging and cancer include autophagy, chromatin and epigenetics, immunology and metabolism.

Research Projects

Nuclear Degeneration in Aging and Cancer

The nucleus is a central cellular entity. Our study suggests that the nucleus undergoes profound degeneration during aging and tumorigenesis. Nuclear components, including nuclear lamina and chromatin, can be degraded by autophagy (Dou et al, Nature, 2015). While autophagy is generally viewed as a cytoplasmic recycling mechanism, the degradation of nuclear materials is beginning to unravel. We are particularly interested in asking:

• What are nuclear and chromatin substrates of autophagy?
• How is nuclear autophagy regulated?
• How does nuclear autophagy impact chromatin and the epigenome?
• What are the functional roles of nuclear degeneration in aging and cancer?

The Biology of Cellular Senescence

Cellular senescence, also referred to as the Hayflick limit, is a stable form of cell cycle arrest. 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 fragments 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 (Dou et al, Nature, 2017). The pro-inflammatory feature of senescence triggers immuno-surveillance of oncogenic cells but contributes to age-associated diseases. We aim to address several fundamental questions of senescence:

• How is cytoplasmic chromatin generated and regulated?
• What is the interaction between senescent cells and the immune system?
• How can we target this pro-inflammatory pathway to treat diseases?

Mechanisms of Mammalian Aging

We are broadly interested in the biology of aging at the molecular, cellular and organismal levels. The laboratory employs multiple mouse models to study alterations of metabolism and the immune system during aging. Our long-term goal is to develop novel approaches to treat age-related diseases and to promote “healthy aging without diseases.”

Research Positions

The Dou lab is currently accepting CVs for the following positions:

Postdoctoral Fellows:
Postdoctoral fellow positions are available in the Dou lab to investigate cutting-edge research topics on aging, cancer, cell biology and epigenetics.

Mass General and Harvard offer unique opportunities for scientific growth and interactions in a highly collaborative and dynamic environment. Candidates are expected to demonstrate a track record of research achievement and have excellent communication skills. Please email Dr. Dou at zdou@mgh.harvard.edu with a cover letter, CV, and contact information for three letters of recommendation.

Research technicians:
We are looking for highly motivated individuals to join our lab. Successful candidates will work directly with scientists on projects investigating aging and cancer and will be exposed to sophisticated experimental approaches including viral genetics, advanced imaging and mouse models of diseases.

Two or more years’ commitment required (special occasions will be considered). Previous research experiences in molecular and cellular biology strongly preferred. Mouse experience preferred but not required. Please email Dr. Dou at zdou@mgh.harvard.edu with a cover letter, CV, and contact information for three letters of recommendation.

Publications

Full list of publications