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Erkki Ruoslahti

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Erkki Ruoslahti
Born (1940-02-16) 16 February 1940 (age 84)
Imatra, Finland
NationalityUS, Finland
Alma materUniversity of Helsinki, Finland
Known forWork on cell adhesion and nanomedicine
Awards
Robert J. and Claire Pasarow Foundation Medical Research Award (Cancer, 1990)
Scientific career
FieldsCancer, Tumor biology, Vascular biology, Neurodegeneration
Institutions

Erkki Ruoslahti (born 16 February 1940 in Imatra, Finland) is a cancer researcher and distinguished professor at Sanford Burnham Prebys Medical Discovery Institute.[1] He moved from Finland to the United States in 1976.[2]

Ruoslahti made seminal contributions to biology of extracellular matrix and its receptors.[3] He was one of the discoverers of fibronectin, an adhesion molecule and component of extracellular matrices, and he subsequently identified and cloned a number of other extracellular matrix components and adhesion molecules. In 1984, he identified the sequence within fibronectin that mediates cell attachment, called RGD for the amino acids of which it’s composed,[4] and isolated the cellular receptors that bind that sequence, now known as integrins.[5] The RGD discovery has led to the development of drugs for vascular thrombosis and cancer, among other diseases.[6]

Ruoslahti currently studies specific marker molecules in blood vessels. He introduced the concept of vascular "zip codes," the idea that each tissue bears molecular signatures that can be targeted by affinity ligands, and used in vivo peptide phage display to prove the concept and develop numerous tumor-homing peptides.[7]

Education

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Ruoslahti received his M.D. from the University of Helsinki in 1965 and his Ph.D. from the same institution in 1967. He completed postdoctoral studies at Caltech.

Career

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Ruoslahti held various academic appointments with the University of Helsinki and the University of Turku in Finland and City of Hope National Medical Center in Duarte, California until joining the La Jolla Cancer Research Foundation (now Sanford Burnham Prebys Medical Discovery Institute, or SBP) in 1979. He served as SBP's president from 1989-2002, and was a distinguished professor at the University of California, Santa Barbara from 2005-2015.

Recent work on homing peptides and nanomedicine

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Ruoslahti's research group has developed a novel class of tumor-homing peptides that can be used to enhance delivery of drugs and nanoparticles to tumors.[8][9] These tumor-penetrating peptides selectively home to tumor vessels, where they activate a transport pathway that delivers the peptide, and along with it drugs and even nanoparticles, through the wall of tumor blood vessels and deep into tumor tissue. Having bound to tumor vessels the peptide is cleaved and an amino acid sequence motif named the C-end rule or CendR motif (pronounced "sender") is exposed at the C-terminus of the peptide. Subsequent binding of the peptide to neuropilin-1 activates the CendR transport pathway into and through tumor tissue.[10][11]

The prototype tumor-penetrating peptide, iRGD, is in clinical trials in solid tumor patients tested as an enhancer of cancer therapies.[12] This peptide recognizes many different types of cancers, and it can be used for tumor delivery of various payloads that are either coupled to the peptide, or given together with it.[9][13][14][15][16][17] iRGD has also been shown to effectively deliver drugs to the placenta, which could aid in the treatment of slow fetal growth.[18]

Recently, in vivo phage screening has been used to identify peptides that target hypertensive pulmonary arteries,[19] atherosclerosis,[20] and diseases of the brain.[21]

Awards and honors

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References

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Scholia has an author profile for Erkki Ruoslahti.
  1. ^ "Erkki Ruoslahti". Sanford Burnham Prebys Medical Discovery Institute. Retrieved October 30, 2017.
  2. ^ Closing In on Cancer : In Search of a Cure, a La Jolla Research Center Reaches Into the Outer Limits Los Angeles Times
  3. ^ Ruoslahti, E; Pierschbacher, MD (1987). "New perspectives in cell adhesion: RGD and integrins". Science. 238 (4826): 491–497. Bibcode:1987Sci...238..491R. doi:10.1126/science.2821619. PMID 2821619.
  4. ^ Pierschbacher, MD; Ruoslahti, E (1984). "Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule". Nature. 309 (5963): 30–33. Bibcode:1984Natur.309...30P. doi:10.1038/309030a0. PMID 6325925. S2CID 4371931.
  5. ^ Dedhar, S; Ruoslahti, E; Pierschbacher, MD (1987). "A cell surface receptor complex for collagen type I recognizes the Arg-Gly-Asp sequence". J Cell Biol. 104 (3): 585–593. doi:10.1083/jcb.104.3.585. PMC 2114550. PMID 3469204.
  6. ^ Ley, K; Rivera-Nieves, J; Sandborn, WJ; Shattil, S (2016). "Integrin-based therapeutics: biological basis, clinical use and new drugs". Nat Rev Drug Discov. 15 (3): 173–183. doi:10.1038/nrd.2015.10. PMC 4890615. PMID 26822833.
  7. ^ Ruoslahti, E. (2004). "Vascular zip codes in angiogenesis and metastasis". Biochem Soc Trans. 32 (3): 397–402. doi:10.1042/bst0320397. ISSN 0300-5127. PMID 15157146.
  8. ^ Teesalu, T.; Sugahara, K. N.; Kotamraju, V. R.; Ruoslahti, E. (2009). "C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration". Proc Natl Acad Sci USA. 106 (38): 16157–16162. Bibcode:2009PNAS..10616157T. doi:10.1073/pnas.0908201106. PMC 2752543. PMID 19805273.
  9. ^ a b Sugahara, K. N.; Teesalu, T.; Karmali, P. P.; Kotamraju, V. R.; Agemy, L.; Girard, O. M.; Hanahan, D.; Mattrey, R. F.; Ruoslahti, E. (2009). "Tissue-Penetrating Delivery of Compounds and Nanoparticles into Tumors". Cancer Cell. 16 (6): 510–520. doi:10.1016/j.ccr.2009.10.013. PMC 2791543. PMID 19962669.
  10. ^ Pang, HB; Braun, GB; Friman, T; Aza-Blanc, P; Ruidiaz, ME; Sugahara, KN; Teesalu, T; Ruoslahti, E (2014). "An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability". Nat Commun. 5: ncomms5904. Bibcode:2014NatCo...5.4904P. doi:10.1038/ncomms5904. PMC 4185402. PMID 25277522.
  11. ^ Pang, HB; Braun, GB; Ruoslahti, E (2015). "Neuropilin-1 and heparan sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides". Sci Adv. 1 (10): e1500821. Bibcode:2015SciA....1E0821P. doi:10.1126/sciadv.1500821. PMC 4640594. PMID 26601141.
  12. ^ "Compound discovered at Sanford Burnham Prebys advances into Phase 1 trial for pancreatic cancer | SBP".
  13. ^ "Cancer Drug Effectiveness Substantially Advanced". Archived from the original on May 7, 2010. Retrieved April 17, 2010.
  14. ^ Sugahara, K. N.; Teesalu, T.; Karmali, P. P.; Kotamraju, V. R.; Agemy, L.; Greenwald, D. R.; Ruoslahti, E. (2010). "Coadministration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs". Science. 328 (5981): 1031–1035. Bibcode:2010Sci...328.1031S. doi:10.1126/science.1183057. PMC 2881692. PMID 20378772.
  15. ^ Couzin-Frankel, Jennifer (8 April 2010). "New Peptide Helps Cancer Drugs Break Into Tumors". ScienceNOW. Archived from the original on June 8, 2013. Retrieved March 14, 2013.
  16. ^ Agemy, L; Kotamraju, VR; Friedmann-Morvinski, D; Sharma, S; Sugahara, KN; Ruoslahti, E (2013). "Proapoptotic Peptide-Mediated Cancer Therapy Targeted to Cell Surface p32". Mol Ther. 21 (12): 2195–2204. doi:10.1038/mt.2013.191. PMC 3863797. PMID 23959073.
  17. ^ Sharma, S; Kotamraju, VR; Mölder, T; Tobi, A; Teesalu, T; Ruoslahti, E (2017). "Tumor-Penetrating Nanosystem Strongly Suppresses Breast Tumor Growth". Nano Lett. 17 (3): 1356–1364. Bibcode:2017NanoL..17.1356S. doi:10.1021/acs.nanolett.6b03815. PMC 5819594. PMID 28178415.
  18. ^ King, A; Ndifon, C; Lui, S; Widdows, K; Kotamraju, VR; Agemy, L; Teesalu, T; Glazier, JD; Cellesi, F; Tirelli, N; Aplin, JD; Ruoslahti, E; Harris, LK (2016). "Tumor-homing peptides as tools for targeted delivery of payloads to the placenta". Sci Adv. 2 (5): e1600349. Bibcode:2016SciA....2E0349K. doi:10.1126/sciadv.1600349. PMC 4928982. PMID 27386551.
  19. ^ Toba, M; Alzoubi, A; O’Neill, K; Abe, ohtaro; Urakami, T; Komatsu, M; Alvarez, D; Järvinen, TAH; Mann, D (2014). "A Novel Vascular Homing Peptide Strategy to Selectively Enhance Pulmonary Drug Efficacy in Pulmonary Arterial Hypertension". Am J Pathol. 184 (2): 369–375. doi:10.1016/j.ajpath.2013.10.008. PMC 3906494. PMID 24401613.
  20. ^ She, ZG; Hamzah, J; Kotamraju, VR; Pang, HB; Jansen, S; Ruoslahti, E (2016). "Plaque-penetrating peptide inhibits development of hypoxic atherosclerotic plaque". J Control Release. 238: 212–220. doi:10.1016/j.jconrel.2016.07.020. PMID 27423327.
  21. ^ Mann, AP; Scodeller, P; Hussain, S; Joo, J; Kwon, E; Braun, GB; Mölder, T; She, Z; Kotamraju, VR; Ranscht, B; Krajewski, S; Teesalu, T; Bhatia, S; Sailor, MJ; Ruoslahti, E (2016). "A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries". Nat Commun. 7: 11980. Bibcode:2016NatCo...711980M. doi:10.1038/ncomms11980. PMC 4931241. PMID 27351915.
  22. ^ Albert Lasker Award for Basic Medical Research.
  23. ^ AACR Academy Fellows: Erkki Ruoslahti.
  24. ^ "Erkki Ruoslahti". United States National Academy of Sciences. Retrieved 14 March 2013.
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