p53 · Genome regulation · Cancer
Decoding how p53 protects cells from cancer
We investigate how wild-type and mutant p53 control transcription, cell-cycle checkpoints and cell fate—and how those mechanisms can be used to improve cancer therapy.
Our research
One pathway.
Many cell fates.
The p53 pathway sits at a decisive point between repair, arrest, senescence and cell death. Our laboratory studies this decision system from molecular interactions and genome occupancy to genetically defined models of tumor suppression. A central goal is to understand why different TP53 mutations produce distinct biological consequences, and to identify vulnerabilities that can be translated into more precise therapeutic strategies.
Read about our research programmes →Research programmes
What we study
Mutant p53 biology
We examine how different TP53 mutations combine loss of tumor-suppressive activity with mutation-specific, context-dependent neomorphic functions.
Learn more →02DNA-damage checkpoints
We define how p53 coordinates reversible arrest, mitotic entry and recovery after transient or sustained genotoxic stress.
Learn more →03Cell-fate decisions
We study how p53-dependent gene regulation is integrated with p21, apoptotic pathways and cellular cofactors to choose arrest, senescence or death.
Learn more →04The p53 regulatory network
We investigate the cofactors, protein modifications and feedback loops that tune p53 transcriptional output and tumor suppression.
Learn more →
Principal investigator
James J. Manfredi, PhD
Professor of Oncological Sciences
James J. Manfredi is Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, with additional appointments in graduate education and stem cell biology and regenerative medicine. His research has defined mechanisms through which p53 coordinates DNA-damage checkpoints, transcriptional regulation and cell-fate outcomes, while recent work examines the diverse neomorphic activities of mutant p53.
Meet the lab →Join the lab