Riccardo_Cortese

Riccardo Cortese

Riccardo Cortese

Italian scientist and entrepreneur


Riccardo Cortese (Siena, Italy, March 29, 1944 – Basel, Switzerland, April 27, 2017) was an Italian scientist, entrepreneur, and innovator in the field of gene expression, drug discovery and genetic vaccines. His work led to the development of novel therapeutic strategies for the prevention and cure of viral infections, including HIV, HCV, Ebola and RSV. He pioneered a novel platform technology based on simian adenoviral vectors for prophylactic and therapeutic vaccines, and authored more than 300 publications in peer-reviewed journals in the field of gene expression, transcriptional control, molecular virology and immunology.

Quick Facts Born, Died ...

Education

Riccardo Cortese received his medical degree in 1968 from the University of Naples, Italy. Shortly after, he joined the lab of Bruce Ames at the University of California Berkeley as a PhD student, where he studied transcriptional regulation and RNA post-transcriptional modification in bacteria. In 1973, he returned to Naples as an assistant professor at the Institute of Biochemistry of the II Medical School, where he pursued research efforts investigating post-transcriptional modifications of tRNA dealing in particular with tRNA pseudouridylation.[1][2][3]

Scientific career

In 1976 he took a post-doctoral position at the MRC Laboratory of Molecular Biology in Cambridge, England, where he forged lasting professional relationships with leading figures in Molecular Biology, including Max Perutz, John Gurdon, Fred Sanger and Sydney Brenner. While at the MRC, his research focus was the maturation of tRNAs in eukaryotic systems.[4][5][6][7]

In 1979 Cortese was recruited as Group Leader at the EMBL-Heidelberg, and subsequently established and directed the Gene Expression Programme (now the Genome Biology Unit).[citation needed]

During this period, Cortese and his lab published numerous seminal papers on the transcriptional regulation of RNA polymerase III-transcribed genes[8][9][10][11][12][13] and on liver-specific gene expression. To identify gene products enriched in the liver, he undertook the first ever direct DNA sequencing experiment on tissue-specific cDNAs libraries.[14]

In 1990, Cortese left EMBL to found and direct the Istituto di Ricerche di Biologia Molecolare (IRBM) in Pomezia (Rome, Italy), a joint venture between Merck and Sigma Tau, where he remained until 2006. In 2000, Merck bought out the shares it did not own in IRBM, making it a fully owned subsidiary.[citation needed]

At IRBM, Cortese created an internationally renowned research center with approximately 200 employees. IRBM's research focus was the development of drugs and vaccines for the treatment of infectious diseases. He used Phage display technology to isolate peptides for diagnostic and vaccination purposes.[15][16][17][18][19][20][21][22][excessive citations]

A substantial research effort at IRBM was in drug discovery aimed at identifying inhibitors of the hepatitis C virus (HCV), a virus that had been recently discovered but not yet fully characterized. The work at IRBM elucidated key features of the HCV replication cycle[23][24][25] and infection mechanisms[26] and positioned the IRBM among the leading research centers in the field of HCV. This work would later inform the development of a novel class of antiretroviral agents, HIV integrase inhibitors, and ultimately of an approved drug product, Isentress, the first anti-integrase of HIV to reach the market.[27][28][29][30]

In his last years at IRBM, Cortese oversaw the development of a new approach to vaccines based on chimpanzee adenoviral vectors.[31] This became the founding idea of Okairos, a biotech company that he founded in 2007 upon leaving IRBM.[citation needed]

With Okairos, Cortese made major scientific contributions, establishing a successful pipeline of candidate vaccines against HCV, malaria, RSV and Ebola. These vaccines were tested in animal models and in clinical trials, demonstrating safety and immunogenicity[32][33][34][35][36][37][38][39][40][excessive citations]

The success of Okairos led to its acquisition by Glaxo-Smith Kline (GSK) in 2013; from that date the company changed its name to ReiThera, and continued independent work in the further development and manufacture of viral vector-based therapeutics and vaccines.

In 2015, Cortese founded a new company, Nouscom, dedicated to the generation of anti-cancer vaccines.

During his career, Cortese received many academic and professional recognitions. Among others, he was elected member of the Academia Europaea; associate foreign member of the Academie des Sciences; elected Member of the Council of the European Molecular Biology Organization; President of the Italian Society of Life Science (FISV); and recipient of the Assobiotec Award in 2017.

Death

Cortese died in Basel, Switzerland on April 27, 2017, of metastatic cancer. He was survived by his wife of almost 50 years, Karen Jonkman, two children, and five grandchildren.


References

  1. Singer, Cliff E.; et al. (1972). "Mutant tRNAHis ineffective in repression and lacking two pseudouridine modifications". Nature New Biology. 238 (81): 72–74. doi:10.1038/newbio238072a0. PMID 4558263.
  2. Cortese, Riccardo; et al. (1974). "Biosynthesis of pseudouridine in transfer Ribonucleic Acid". Journal of Biological Chemistry. 249 (4): 1103–1108. doi:10.1016/S0021-9258(19)42947-5. PMID 4592259.
  3. Cortese, Riccardo; et al. (1974). "Pleiotrophy of hisT mutants blocked in pseudouridine synthesis in tRNA: leucine and isoleucine-valine operons". Proceedings of the National Academy of Sciences of the United States. 71 (5): 1857–1861. Bibcode:1974PNAS...71.1857C. doi:10.1073/pnas.71.5.1857. PMC 388341. PMID 4151955.
  4. Cortese, R.; et al. (1980). "Transcription of tRNA genes in vivo: Single-stranded compared to double-stranded templates". Proceedings of the National Academy of Sciences of the United States of America. 77 (7): 4147–4151. Bibcode:1980PNAS...77.4147C. doi:10.1073/pnas.77.7.4147. PMC 349787. PMID 7001455.
  5. Melton, D. A.; et al. (1980). "Order and intracellular location of the events involved in the maturation of a spliced tRNA". Nature. 284 (5752): 143–148. Bibcode:1980Natur.284..143M. doi:10.1038/284143a0. PMID 6987526. S2CID 4234355.
  6. Ciampi, M. S.; et al. (1982). "Site-directed mutagenesis of a tRNA gene: base alterations in the coding region affect transcription". Proceedings of the National Academy of Sciences of the United States of America. 79 (5): 1388–1392. Bibcode:1982PNAS...79.1388C. doi:10.1073/pnas.79.5.1388. PMC 345978. PMID 6951183.
  7. Ciliberto, G.; et al. (1982). "Promoter of a eukaryotic tRNAPro gene is composed of three noncontiguous regions". Proceedings of the National Academy of Sciences of the United States of America. 79 (4): 1195–1199. Bibcode:1982PNAS...79.1195C. doi:10.1073/pnas.79.4.1195. PMC 345928. PMID 6951168.
  8. Ciliberto, G.; et al. (1982). "Relationship between the two components of the split promoter of eukaryotic tRNA genes". Proceedings of the National Academy of Sciences of the United States of America. 79 (6): 1921–1925. Bibcode:1982PNAS...79.1921C. doi:10.1073/pnas.79.6.1921. PMC 346093. PMID 6952243.
  9. Ciliberto, G.; et al. (1983). "Common and interchangeable elements in the promoters of genes transcribed by RNA polymerase III". Cell. 32 (3): 725–733. doi:10.1016/0092-8674(83)90058-2. PMID 6299574. S2CID 6357594.
  10. Traboni, C.; et al. (1984). "Mutations in Box B of the promoter of a eucaryotic tRNAPro gene affect rate of transcription, processing, and stability of the transcripts". Cell. 36 (1): 179–187. doi:10.1016/0092-8674(84)90087-4. PMID 6559106. S2CID 33914591.
  11. Cortese, Riccardo; et al. (1995). "Identification of biologically active peptides using random libraries displayed on phage". Current Opinion in Biotechnology. 6 (1): 73–80. doi:10.1016/0958-1669(95)80012-3. PMID 7534506.
  12. Martin, Franck; et al. (1996). "Coupling protein design and in vitro selection strategies: improving specificity and affinity of a designed β-protein IL-6 antagonist". Journal of Molecular Biology. 255 (1): 86–97. doi:10.1006/jmbi.1996.0008. PMID 8568877.
  13. Galfrè, Giovanni; et al. (1996). "Immunization with phage-displayed mimotopes". Combinatorial Chemistry. Methods in Enzymology. Vol. 267. pp. 109–115. doi:10.1016/S0076-6879(96)67008-6. ISBN 9780121821685. PMID 8743312.
  14. Cortese, I.; et al. (1996). "Identification of peptides specific for cerebrospinal fluid antibodies in multiple sclerosis by using phage libraries". Proceedings of the National Academy of Sciences of the United States of America. 93 (20): 11063–11067. Bibcode:1996PNAS...9311063C. doi:10.1073/pnas.93.20.11063. PMC 38284. PMID 8855309.
  15. Steinkühler, Christian; et al. (1998). "Product inhibition of the hepatitis C virus NS3 protease". Biochemistry. 37 (25): 8899–8905. doi:10.1021/bi980313v. PMID 9636031.
  16. Summa, Vincenzo; et al. (2004). "Discovery of alpha,gamma-diketo acids as potent selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase". Journal of Medicinal Chemistry. 47 (1): 14–17. doi:10.1021/jm0342109. PMID 14695815.
  17. Summa, Vincenzo; et al. (2004). "HCV NS5b RNA-dependent RNA polymerase inhibitors: from alpha,gamma-diketoacids to 4,5-dihydroxypyrimidine- or 3-methyl-5-hydroxypyrimidinonecarboxylic acids. Design and synthesis". Journal of Medicinal Chemistry. 47 (22): 5336–5339. doi:10.1021/jm0494669. PMID 15481971.
  18. Petrocchi, Alessia; et al. (2007). "From dihydroxypyrimidine carboxylic acids to carboxamide HIV-1 integrase inhibitors: SAR around the amide moiety". Bioorganic & Medicinal Chemistry Letters. 17 (2): 350–353. doi:10.1016/j.bmcl.2006.10.054. PMID 17107799.
  19. Hazuda, Daria J.; et al. (2004). "A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase". Proceedings of the National Academy of Sciences of the United States of America. 101 (31): 11233–11238. doi:10.1073/pnas.0402357101. PMC 509174. PMID 15277684.
  20. Folgori, A.; et al. (2006). "A T-cell based HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees". Nature Medicine. 12 (2): 190–197. doi:10.1038/nm1353. PMID 16462801. S2CID 24882355.
  21. Stanley, Daphne A.; et al. (2014). "Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge". Nature Medicine. 20 (10): 1126–1129. doi:10.1038/nm.3702. PMID 25194571. S2CID 20712490.
  22. Ledgerwood, Julie E.; et al. (2017). "Chimpanzee Adenovirus Vector Ebola Vaccine". The New England Journal of Medicine. 376 (10): 928–938. doi:10.1056/NEJMoa1410863. PMID 25426834. S2CID 205097251.
  23. Ewer, Katie; et al. (2016). "A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA". The New England Journal of Medicine. 374 (17): 1635–1646. doi:10.1056/NEJMoa1411627. PMC 5798586. PMID 25629663. S2CID 73185008.

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