Cell survival and DNA repair in mammals
Stress is an unavoidable aspect of life. Cells are constantly
exposed to damage, but some cells repair damage and continue
growing normally, while other cells suffer apoptosis, senescence
or become malignant. The biological reasons for these differing
responses to stress are not clear, but the consequences in terms
of health (especially in aging and cancer) are profound. The goal
of my research program is to show why different cells respond
differently to stress, with the goal of reprogramming cells so
that they repair damage in an advantageous way.
We previously showed that mutation and cancer arise in cells
lacking the BRCA1 tumor suppressor gene as a consequence of the
cellular response to DNA damage. By targeting specific damage
response factors in these cells, it is possible to prevent
mutation, and select for healthy cell growth. We aim to build on
this work to better understand differences between damage response
pathways in different cell types. For example,
• Do stem cells react to damage differently from somatic cells?
• What mechanisms regulate choice of DNA repair pathways?
• Do damage responses affect the chromatin environment of the
• Is it possible to identify drugs or other treatments that bias
cellular damage responses?
We study these questions in mice using a variety of molecular and
biochemical techniques with a particular focus on DNA repair. By
using genetically-targeted mouse strains, we aim to explore the
full complexity of mechanisms regulating the response to damage in
a long-lived mammalian species with significant homology to