Sassone-Corsi's work largely focused on the implementation of molecular approaches for
cell signaling,
circadian rhythm,
epigenetics, and the plasticity of the genome. Through the study of signal transduction mechanisms, he investigated how they modulate nuclear functions such as gene expression, chromatin remodeling, and epigenetic control.
Early research on transcription During his time as a postdoc, working under the mentorship of
Pierre Chambon at IGBCM in 1980, Sassone-Corsi studied transcriptional elements and identified the promoter sequence of the adenovirus major late gene, which later became known as the
TATA box. Later, Sassone-Corsi moved to the Salk Institute for Biological Studies and made important advancements in understanding the transcriptional autoregulation of the proto-oncogene,
fos. Oncogenes which encode for nuclear proteins include,
fos, jun, and
p53, just to name a few. As a nuclear oncogene,
fos is able to initiate cell growth, differentiation, and development which can cause cancer if over-induced. The c-fos protein contains a "
leucine zipper" that allows it to form a heterodimer with
jun, another oncogene.
Circadian biology research In 2006, Sassoni-Corsi illuminated the role of
chromatin remodeling in circadian mechanisms through the discovery that
CLOCK acts as a
histone acetyltransferase (HAT) by recruiting
P300 and CBP, allowing it to help restore rhythmicity in
Clock mutants. This activity allows CLOCK to control the acetylation of
BMAL1 and
H3. This was important in demonstrating the role of chromatin remodeling in the core clock mechanism and revealed new associations between cellular physiology and histone acetylation. He later helped discover that the
histone deacetylase (HDAC) activity of
SIRT1, which is
NAD+ dependent, undergoes circadian regulation, counteracts the HAT activity of CLOCK, and has
in vivo circadian control. In 2009, Sassone-Corsi also helped discover that
NAMPT, a rate-limiting step involved in NAD+ salvaging, has circadian expression regulated by CLOCK:BMAL1. His research found that NAMPT was essential to altering the circadian expression of genes; in the same study, he discovered a transcriptional-enzymatic feedback loop between circadian rhythms and cellular metabolism which was an impactful contribution to investigating the links between the two.
Signaling pathways Sassone-Corsi was influential in investigating the role of
chromatin in signaling with a study he conducted in 2000. He revealed that signaling pathways act directly on chromatin components to regulate certain processes; N-terminal tails of histones are acted upon with reversible covalent modifications to elicit responses in multiple pathways. They investigated the interactions that occur when multiple modifications are present on the N-terminal tails at the same time and proposed that H2B-H3 and H2A-H4 are the tails which act as signaling platforms. His research segued into a broader understanding of the role histone modifications play in the complex circuitries of gene regulation. He identified that EGF stimulation activates the
MAP kinase pathway which leads to sequential modifications of chromatin. ==Honors and awards==