Erkki Ruoslahti, M.D., Ph.D.

Erkki Ruoslahti, M.D., Ph.D., headshot

Erkki Ruoslahti, M.D., Ph.D.

Distinguished Professor Emeritus

Erkki Ruoslahti's Research Focus

Cancer, Brain Cancer, Breast Cancer, Prostate Cancer, Atherosclerosis, Alzheimer's Disease

The Ruoslahti laboratory studies peptides that home to specific targets in the body, such as tumors, atherosclerotic plaques and injured tissues. These peptides, which usually bind to receptors in the vessels of the target tissue, can be used to selectively deliver diagnostic probes and drugs to the target. The latest development is the discovery of homing peptides with tumor-penetrating properties. The CendR tissue penetration pathway  is a new endocytosis/trans-tissue transport pathway (Pang et al., Nat Comm. 2014). The current focus is on enhancing the effects of coupled and co-injected drugs with the tumor-homing peptides, particularly in mouse models of breast cancer and glioblastoma. This laboratory also studies the receptors for the peptides and the mechanism of their tumor penetration activity.

Erkki Ruoslahti's Research Report

Dr. Ruoslahti’s main scientific contributions are in the field of cell adhesion. He was one of the discoverers of fibronectin.  His laboratory subsequently discovered the RGD cell attachment sequence in fibronectin and isolated RGD-directed cellular receptors, now known as integrins. The RGD discovery has led to the development of drugs for diseases ranging from vascular thrombosis to cancer. 

Dr. Ruoslahti current studies deal with peptides that specifically target a diseased tissue, particularly its blood vessels. The peptides can be used to deliver drugs and nanoparticles to sites of disease, such as a tumor. The molecules targeted by such disease-specific peptides are of interest regarding their possible role in the disease and potential targets for drug development.


Vascular Zip Codes

The Ruoslahti laboratory screens large collections ("libraries") of random peptides to identify those that bind to specific targets in tissues. The peptides in the library are displayed on the surface of phage (a virus that infects bacteria), and the screening is done in vivo. When the library is injected into the circulation of a mouse, phage particles that display peptides capable of binding to a selected target tissue, such as a tumor, accumulate at the target where they can be collected and their peptide identified. The process primarily probes the vasculature of the target tissue, unless the vasculature is very leaky. The method has revealed a wealth of specific features, or "vascular zip codes", in the vessels of individual tissues and tumors. Peptides that specifically home to tumors because they recognize angiogenesis-associated or tumor-type specific markers in tumor blood vessels and can even distinguish the vessels of pre-malignant lesions from those of fully malignant tumors. Homing peptides have also revealed a zip code system of molecular changes in tumor lymphatics.

Synthetic homing peptides have been used to target drugs, biologicals, and nanoparticles into tumors. The targeting can increase the efficacy of a drug while reducing its side effects. Even a non-specifically toxic compound can be converted into a compound that selectively affects the targeted tissue. The peptides make it possible to identify the target molecules (receptors) for the peptides. The receptors of tumor-homing peptides often play a functionally important role in tumor vasculature, and because of this are candidates for drug development.


Tumor-penetrating peptides

A few years ago the laboratory discovered peptides that not only home to tumor vessels, but are transported through the vascular wall and deep into tumor tissue. The key feature of these peptides is a R/KXXR/K sequence motif, named C-end Rule (CendR) motif or element. In tumor-penetrating peptides, the CendR element is cryptic. These peptides penetrate into tumor tissue in a 3-step process: (i) The peptide binds to a primary receptor on tumor endothelium. In iRGD, the RGD motif recognizes the avb3/avb5 integrins; the primary receptor for the LyP-1 family of peptides is cell surface p32/gC1qR. (ii) The peptide is then cleaved by a protease to expose the CendR element at the C-terminus of the peptide; and, (iii) the CendR element mediates binding to neuropilin-1 (NRP-1), to induce vascular and tissue penetration. The CendR transport pathway triggered through NRP-1 resembles macropinocytosis, but differs from it in being receptor-mediated. Importantly, the responsiveness of the pathway to triggering through NRP-1 is regulated by the nutrient status of cells and tissues. Its physiological function is likely to be to transport nutrients into tissues that lack them. Our ability to trigger the pathway specifically in tumors makes it useful in delivering drugs into tumors.


Targeting the brain

The Ruoslahti laboratory has recently also applied phage screening to the identification of peptides that target brain diseases. So far, a peptide that specifically recognizes sites of brain injury, and a panel of peptides that are specific for Alzheimer’s brain have been obtained. This topic will be an expanding focus of the laboratory in the near future.



A major focus is to use homing peptides as targeting elements to deliver nanoparticles into tumors and other sites of disease. Nanoparticles are considered a promising new approach in medicine because they can be designed to perform more functions than a simple drug. The vasculature is an excellent target for nanoparticles because tumor vessels are readily available for circulating particles. In collaboration with chemistry and bioengineering laboratories, multifunctional nanoparticles for tumor targeting have been constructed. These particles can be directed into tumors in a highly selective manner as demonstrated by histology, non-invasive imaging, and tumor treatment results. The laboratory has constructed nanoparticles with the ability to amplify their own homing to tumors, and are currently working on nanoparticles coated with tumor-penetrating peptides. More recent work has dealt with nanoparticles that target brain diseases or atherosclerotic plaques. The general goal is to engineer nanoparticles with multiple functions. In addition to the specific targeting, such functions include avoidance of the reticuloendothelial system, self-amplification of the targeting, exit from vessels into tissue, ability to send signals for imaging, and controlled drug delivery.

Research Report

Schematic representation of the CendR trans-tissue transport pathway

Note that CendR effect enhances the tissue penetration of molecules (depicted here as a black dots) that are co-administered with the peptide, as well as of cargo coupled to the peptide. The inset shows an electron microscopic image of a CendR endocytic vesicle that is budding from the cell surface into the cytoplasm and contains CendR peptide-coated gold nanoparticles (dark dots) See Ruoslahti, Adv. Drug Deliv. Rev. 2016.


Ruoslahti E. Tumor penetrating peptides for improved drug delivery. Adv Drug Deliv Rev. 2016 Apr 1. pii: S0169-409X(16)30094-1. doi: 10.1016/j.addr.2016.03.008. Review. PMID: 27040947

Ruoslahti, E. Peptides as targeting elements and tissue penetration devices for nanoparticles. Adv. Mat. (review article) 24:3747-3756. (2012). PMCID: PMC3947925


Erkki Ruoslahti's Bio

Erkki Ruoslahti earned his M.D. and Ph.D. from the University of Helsinki in Finland in 1967. After postdoctoral training at the California Institute of Technology, he 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. He joined Sanford Burnham Prebys in 1979 and served as its President from 1989-2002. He was a Distinguished Professor at University of California Santa Barbara in Biological Sciences 2005-2015. His honors include elected membership to the U.S. National Academy of Sciences, National Academy of Medicine, American Academy of Arts and Sciences, and the European Molecular Biology Organization, the Japan Prize, Gairdner Foundation International Award, G.H.A. Clowes Award, Robert J. and Claire Pasarow Foundation Award, and Jacobaeus International Prize. He was a Nobel Fellow at the Karolinska Institute in Stockholm in 1995, and is an Honorary Doctor of Medicine from the University of Lund, as well as a Knight and Commander of the Orders of the White Rose the the Lion of Finland. In 2022, Dr. Ruoslahti was announced as one of three winners of the Albert Lasker Basic Medical Research Award.



1966: M.D., University of Helsinki in Finland
1967: Ph.D., University of Helsinki in Finland


Awards and honors

2022: Albert Lasker Award for Basic Medical Research
Commander of the Order of the Lion of Finland
Knight of the Order of the White Rose of Finland
2012: Thomson Reuters Citation Laureate
2005: Japan Prize in Cell Biology
2003: Jubilee Lecturer, Biochemical Society
1998: Jacobaeus International Prize
1997: Gairdner Foundation International Award
1995: Nobel Fellow at the Karolinska Institutet in Stockholm
1991: Honorary doctorate in medicine from Lund University, Sweden
1990: American Association for Cancer Research - G.H.A. Clowes Memorial Award


National Academy of Sciences
National Academy of Medicine
American Academy of Arts and Sciences
European Molecular Biology Organization

TMC Accessory


An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability.

Pang HB, Braun GB, Friman T, Aza-Blanc P, Ruidiaz ME, Sugahara KN, Teesalu T, Ruoslahti E

Nat Commun 2014 Oct 3 ;5:4904

Tumor-penetrating iRGD peptide inhibits metastasis.

Sugahara KN, Braun GB, de Mendoza TH, Kotamraju VR, French RP, Lowy AM, Teesalu T, Ruoslahti E

Mol Cancer Ther 2015 Jan ;14(1):120-8

Tumor penetrating peptides for improved drug delivery.

Ruoslahti E

Adv Drug Deliv Rev 2017 Feb ;110-111:3-12

Show All Select Publications

Author Correction: Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.

Maldonado H, Savage BD, Barker HR, May U, Vähätupa M, Badiani RK, Wolanska KI, Turner CMJ, Pemmari T, Ketomäki T, Prince S, Humphries MJ, Ruoslahti E, Morgan MR, Järvinen TAH

Nat Commun 2024 Jan 3 ;15(1):234

Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.

Maldonado H, Savage BD, Barker HR, May U, Vähätupa M, Badiani RK, Wolanska KI, Turner CMJ, Pemmari T, Ketomäki T, Prince S, Humphries MJ, Ruoslahti E, Morgan MR, Järvinen TAH

Nat Commun 2023 Dec 6 ;14(1):8069

Reflections on Integrins-Past, Present, and Future: The Albert Lasker Basic Medical Research Award.

Hynes RO, Ruoslahti E, Springer TA

JAMA 2022 Oct 4 ;328(13):1291-1292

Molecular ZIP codes in targeted drug delivery.

Ruoslahti E

Proc Natl Acad Sci U S A 2022 Jul 12 ;119(28):e2200183119

iRGD-liposomes enhance tumor delivery and therapeutic efficacy of antisense oligonucleotide drugs against primary prostate cancer and bone metastasis.

Guan J, Guo H, Tang T, Wang Y, Wei Y, Seth P, Li Y, Dehm SM, Ruoslahti E, Pang HB

Adv Funct Mater 2021 Jun 9 ;31(24)

Tumor-penetrating therapy for β5 integrin-rich pancreas cancer.

Hurtado de Mendoza T, Mose ES, Botta GP, Braun GB, Kotamraju VR, French RP, Suzuki K, Miyamura N, Teesalu T, Ruoslahti E, Lowy AM, Sugahara KN

Nat Commun 2021 Mar 9 ;12(1):1541

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