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Each of our cells are regularly challenged by environmental stresses, and proper repair of damage generated by those stresses are important for maintaining the health of our cells. Improper responses to damaging conditions can have far-reaching effects beyond cells, affecting tissue, organ, and organismal functions. 

The Batchelor lab is interested in understanding how cells respond to DNA damage. Improper regulation of cellular DNA damage responses impacts many health issues, including the development of numerous forms of cancer.

Much of our research focuses on damage responses mediated by the tumor suppressor protein p53, which is a major regulator of cell stress responses and which is mutated in half of all cancers. We use methods from quantitative microscopy to understand how p53 regulates the DNA damage response at the level of single cells. Our detailed analysis of p53 in individual cells has led to new insights into the high level of heterogeneity in the DNA damage response across cells. Such heterogeneity is important for understanding rare DNA mutations that can transform healthy cells into cancer cells, as well as heterogeneous responses giving rise to cancer cell resistance to DNA-damaging therapeutic treatments.


Our current work focuses on understanding how p53 dynamics, the temporal patterns of p53 accumulation and degradation, regulate downstream damage responses, including cell cycle arrest, DNA repair, senescence, apoptosis, and metabolism. Our previous work has shown that p53 dynamics can affect different cell stress responses. p53 dynamics have the potential to be controlled by several mechanisms, and therefore a better understanding of the regulation and function of p53 dynamics may be leveraged to provide novel therapeutic approaches to change, restore, or compensate for altered p53 activity.

We are also applying quantitative, single-cell approaches to identify novel modes of regulation between p53 and other important signaling pathways, including the MYC proto-oncogene network and MAPK signaling, which also serve important functions in cell health and the prevention of tumor formation.

Using a combination of experimental and computational approaches, some of the questions we are interested in answering include:

  • How do specific features of different patterns of p53 expression lead to distinct cell fate outcomes? 
  • How do gain-of-functions p53 mutations common in cancer affect p53 dynamics to alter p53 function?
  • How does the coordinated regulation of p53 and MYC dynamics affect different cell stress responses?
  • How do tissue-specific differences in p53 dynamics affect cell stress responses?
  • How does dynamic regulation of other cell signaling pathways, including the MAPK pathways and NF-kB, work in coordination with p53 signaling to affect cell stress responses?

Our long-term vision is that we will identify novel mechanisms to counteract, alleviate, or compensate for improper cellular damage responses at the heart of tumor malignancy and heterogeneous therapeutic responses.