Kelvin Tsai
Yuan Laboratory
Harvard School of Public Health
Circumstantial
evidence supports the theory that the stromal microenvironment plays a crucial
role in breast cancer development and progression. Fibroblasts are a major
constituent of the stroma, which orchestrate the events regulating the stroma-epithelium
crosstalk. Repetitive exposure to environmental stress insults can lead
to accumulation of senescent-like stromal cells in tissue. This stress-induced
premature senescence (SIPS) might serve as a 'backup' to apoptosis as a
global response to stress. However, an emerging concept suggests that fibroblasts
that undergo SIPS can create a microenvironment permissive to carcinogenesis
by mediating extracellular matrix remodeling and altered growth factor signaling.
I am currently pursuing new conceptual and experimental approaches to understanding
the mechanisms underlying the development of the SIPS phenotype in stromal
cells and their contribution to the epigenetic regulation of epithelial
tumorigenesis at the molecular level.