Paolo Sassone-Corsi

Paolo Sassone-Corsi (8 June 1956 – 22 July 2020) was an Italian researcher, molecular biologist, and epigeneticist. He is best known for his contributions in the field of transcriptional regulation, epigenetics, circadian biology, and metabolic regulation. Paolo spent three decades pioneering research on the mechanisms regulating transcription and linking these processes to metabolism and circadian clocks. His studies on the regulation of circadian rhythms are milestones advancements in how the daily dark/light cycles modify our physiology. He is also credited as the founder and directer of the “Center for Epigenetics and Metabolism” at the University of California, Irvine in 2011.

Biography

Paolo Sassone-Corsi was born in Naples, Italy on June 8, 1956. He devoted himself to science at an early age. Together with his brother Emilio Sassone-Corsi, they founded the Neapolitan Astronomy Club (Gruppo Astrofili Napoletani). Their studies were awarded the Philips Prize for Young Researchers. They worked at the Paris Meudon Observatory where they studied Saturn. His passions grew from astronomy to biology, and eventually genetics.

Paolo completed his graduate studies on yeast biology and graduated with a doctorate in biological science from the University of Naples Federico II in 1979. Following this, Sassone-Corsi moved to Strasbourg in December. He obtained a post-doctoral degree under the instruction of Pierre Chambon in Strasbourg at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) in Strasbourg, France. During his time under Chambon, Paolo was drawn to transcription mechanisms and contributed to key work on promoters, enhancers and transactivating factors.

In search of innovation, he and his wife moved to San Diego, United States where he worked under Inder Verma at the Salk Institute for Biological Studies from 1986 to 1989. At the Salk Institute, most of his work was focused on the study of the intracellular pathway that leads to the activation of proto-oncogenes c-''fos'' and c-''jun.''

In 1989, he began working as a research director for the French National Centre for Scientific Research at Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) in Strasbourg, France. He started his own independent laboratory at IGBMC and progressed to the director of research at the Centre National de la Recherche Scientifique.  During his time here, Paolo identified and characterized the role of the cAMP-responsive element modulator (CREM) in spermatogenesis.  

Beginning in 2006, he worked for the University of California, Irvine as a professor and head of chair of the pharmacology department.  In 2011, he founded and directed the Center of Epigenetics and Metabolism. 

During the course of his life, Paolo has published multiple books.In 2013, Sassone-Corsi published a book of reflections titled "Ti sembra il Caso?: Schermaglia fra un narratore e un biologo", written alongside Erri De Luca. He also wrote another book with Erri De Luca. in 2016 about the intersections of biology, music and poetry.

Scientific Contribution

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, 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''. He found that proto-oncogenes ''c-fos'' and ''c-jun'' are activated through a pathway which regulates transcription; ''c-fos'' and ''c-jun'' interact with each other to form AP-1 and ''c-fos'' is regulated by cAMP.

Circadian biology research

Sassoni-Corsi illuminated the role of chromatin remodeling in circadian mechanisms through the discovery that CLOCK acts as a histone acetyltransferase (HAT), allowing it to help restore rhythmicity in ''Clock'' mutants. This activity allows CLOCK to control the acetylation of BMAL1 and H3. 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. He also helped find that NAMPT, an important enzyme involved in NAD+ salvaging, has circadian expression regulated by CLOCK:BMAL1. His research showed that NAMPT was essential to altering the circadian expression of genes, and in the same study, he discovered a transcriptional-enzymatic feedback loop between circadian rhythms and cellular metabolism.

Signaling pathways

Sassone-Corsi was influential in investigating the role of chromatin in signaling. 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.

Sassone-Corsi looked further into the coupling of histone modifications and found evidence of synergistic coupling of H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. He identified that EGF stimulation activates the MAP kinase pathway which leads to sequential modifications of chromatin.

Distinctions

*Philips European Award for Young Investigators (1977)
*Member of the European Molecular Biology Organization (1990)
* Medal of the European Molecular Biology Organization (1994)
* Rosen Prize (Fondation de la Recherche Médicale), France (1996)
* Prix Liliane-Bettencourt (1997)
* Segerfalk Award Lecture, Lund University, Sweden (2001)
* ISI Highly Cited (2003)
* Grand Prix Charles-Leopold Mayer of the French Academy of Sciences (2003)
* Edwin B. Astwood Award Lecture of The Endocrine Society, USA (2004)
* The Umesono Memorial Award Lecture, The Salk Institute, San Diego, USA (2004)
* Silver Medal of the French National Centre for Scientific Research (2004)
* Athalie Clarke Achievement Award, University of California, School of Medicine (2010)
* Roy O. Greep Award Lecture, 2011, Laureate Award by The Endocrine Society (2011)
* The Ipsen Award in Endocrinology, France (2011)
* External Member, Max Planck Society, Germany (2011)
* Transatlantic Medal of The Society for Endocrinology, UK (2012)
* Dr. Henry Friesen Plenary Lecture Award, Canada (2013)
* Fellow, American Association for the Advacement of Science, USA (2014)
* August and Marie Krogh Medal, Denmark (2015)
* Leonardo da Vinci Gold Medal, FMSI Federation, Rome, Italy (2016)
* Albert Hogan Memorial Award Lecture, University of Missouri (2017)
* Distinguished Faculty Award for Research, University of California, Irvine (2019)

Books

*''Germ Cells.'' Cold Spring Harbor Laboratory Press (2011)
*''Epigenetics, Brain and Behavior. '' Springer (2012)
*''Ti sembra il caso?: Schermaglia fra un narratore e un biologo.'' Feltrinelli Editore (2013)
*''Le cas du Hasard: Escarmouches entre un écrivain et un biologiste.'' Galimard (2016)
*''A Time for Metabolism and Hormones.'' Springer (2017)
*''Circadian Rhythms.'' Cold Spring Harbor Laboratory Press (2018)

References

{{DEFAULTSORT:Sassone-Corsi, Paolo
1956 births
2020 deaths
Italian molecular biologists
Scientists from Naples
University of Naples Federico II alumni