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Erkki Ruoslahti

Born	16 February 1940 Imatra, Finland
Nationality	US, Finland
Alma mater	University of Helsinki, Finland
Known for	Work on cell adhesion and nanomedicine
Awards	Robert J. and Claire Pasarow Foundation Medical Research Award (Cancer, 1990) G.H.A. Clowes Memorial Award, American Association for Cancer Research (1990) Nobel Fellow at the Karolinska Institutet, Stockholm (1995) Gairdner Foundation International Award (1997) Jacobaeus International Prize (1998) Jubilee Lecturer, Biochemical Society (2003) Japan Prize (Cell Biology, 2005) Thomson Reuters Citation Laureate (2012)
Scientific career
Fields	Cancer, Tumor biology, Vascular biology, Neurodegeneration
Institutions	California Institute of Technology University of Turku City of Hope National Medical Center Sanford Burnham Prebys Medical Discovery Institute

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]

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Transcription

My early research had to do with cell adhesion. Although I started it many more years ago than I care to think about, I still do some of that work and my recent work is a derivation of it. What we set out to do is to understand what keeps normal cells in their place in the body. The original hypothesis was that there would be a cell surface recognition mechanism that accomplished this task, and of course no molecules were known at that time that would work in such a way, so it was all new. But that led us, experiments that we developed to study this possibility led us to what we later on named fibronectin, which is a prototype cell adhesion molecule. Then we worked on fibronectin and particularly on its cell attachment site which we got down to a very small peptide that has then became the basis of some drugs and is still much used in the clinic and in clinical trials and so on. We then also identified receptors that bind to this peptide, now known as integrins. The cell attachment site we identified in fibronectin consists only of three amino acids: arginine, glycine and aspartic acid and by the one letter code that is currently mostly used, it translates into: RGD. So the RGD peptide was remarkable because it so small. The fibronectin molecule has 3,000 amino acids, almost 3,000 amino acids, and yet only 3 of them were the key to the, to the binding of cells to the aspartate. The use of RGD in the clinic, the first uses, were to inhibit, prevent the aggregation of the small blood cells that cause blood clotting and participate in blood clotting the platelets. It turns out they aggregate based on this RGD integrin chemistry and that could be inhibited with the soluble RGD peptides. Now, it then turns out that the peptides themselves also have an effect on cancer and there is one drug in clinical trials that makes use of the ability of RGD to prevent the growth of tumor cells, or it actually effects more the blood vessels that nurture the tumor. So, currently my laboratory works on what I call, vascular “zip codes”. We found a way of studying the vasculature in a live mouse, looking for differences in the inner lining of blood vessels from one tissue to another, from one pathology to another and so forth. And it turns out there is a tremendous amount of heterogeneity in the inner lining of blood vessels even though they pretty much look the same, but molecularly they are not the same. Tissues and pathological lesions put their signature on their vasculature, and we find those signatures and one of the signatures actually is the integrins that bind to RGD. So RGD peptides are used a lot to deliver things directly into tumors.

Education

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

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

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]