Manfredi Labp53 Biology · Icahn School of Medicine at Mount Sinai

Research

How p53 controls damage, fate and cancer

Our programmes connect TP53 variation and genome regulation with cell-cycle checkpoints, cell-fate decisions and therapeutic response.

01

Mutant p53 biology

We examine how different TP53 mutations combine loss of tumor-suppressive activity with mutation-specific, context-dependent neomorphic functions.

Central question

Which mutant p53 activities are shared, which are allele-specific, and which depend on tissue context?
Explore this programme →
Mutant p53 gain-of-function activity regulates tumor cell-intrinsic mechanisms.
Mutant p53 gain-of-function activity regulates tumor cell-intrinsic mechanisms.
02

DNA-damage checkpoints

We define how p53 coordinates reversible arrest, mitotic entry and recovery after transient or sustained genotoxic stress.

Central question

How does p53 prevent damaged cells from entering or progressing through mitosis?
Explore this programme →
dm2 contributes to cell cycle arrest and prevents apoptosis.Following stress, p53 activates different transcriptional programs resultingin cell cycle arrest or apoptosis.
dm2 contributes to cell cycle arrest and prevents apoptosis.Following stress, p53 activates different transcriptional programs resultingin cell cycle arrest or apoptosis.
03

Cell-fate decisions

We study how p53-dependent gene regulation is integrated with p21, apoptotic pathways and cellular cofactors to choose arrest, senescence or death.

Central question

What determines whether p53 activation produces survival and repair or irreversible cell elimination?
Explore this programme →
Cellular stress induces p53‐dependent responses. In response to cellular stress such as DNA damage, the p53 protein becomes stabilized. In the nucleus, p53 binds to specific promoters and activates transcription of its target genes.
Cellular stress induces p53‐dependent responses. In response to cellular stress such as DNA damage, the p53 protein becomes stabilized. In the nucleus, p53 binds to specific promoters and activates transcription of its target genes.
04

The p53 regulatory network

We investigate the cofactors, protein modifications and feedback loops that tune p53 transcriptional output and tumor suppression.

Central question

How do MDM2, the p53 C terminus and chromatin context reshape the p53 response?
Explore this programme →