Kazuki Sugahara, MD, PHD
Kazuki N. Sugahara, MD, PhD, is an Assistant Professor of Surgery. Dr. Sugahara studies drug delivery systems to enhance the diagnosis and therapy of various cancers, particularly pancreatic cancer. He has developed various tumor-targeting peptides that deliver compounds selectively to cancer tissue, and reported them in a number of high-profile journals such as Science. One of his peptides, the iRGD tumor-penetrating peptide, is now in a first-in-human Phase 1 clinical trial for metastatic pancreatic cancer. Dr. Sugahara’s work has been recognized through grants and awards from national agencies such as the NIH, Department of Defense, and Pancreatic Cancer Action Network, and also from international societies such as the Japan Society of Drug Delivery Systems.
After receiving his medical degree from Shiga University of Medical Science in Japan, Dr. Sugahara underwent surgery residency at Tazuke Kofukai Kitano Hospital, Osaka, Japan, received a PhD in cancer biology and immunology from the Osaka University Graduate School of Medicine, Japan, and completed a postdoctoral fellowship at the Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California. He came to Columbia University in 2013 to take dual appointment as a categorical resident and a research faculty at the Department of Surgery. He now continues to pursue his career as a surgeon scientist with a special focus on pancreatic cancer.
Finalist, Poster Competition, Society of Surgical Oncology Annual Meeting (USA, 2019)
Blakemore Award, 1st Annual Research Symposium, Columbia University (USA, 2017)
2nd Place, Annual Research Competition, Department of Surgery, Columbia University (USA, 2016)
Finalist, Poster Competition, Society of Surgical Oncology Annual Meeting (USA, 2015)
John Jones Surgical Society Award, Columbia University (USA, 2014)
Career Development Award, AACR-Pancreatic Cancer Action Network (USA, 2012)
Idea Expansion Award, Breast Cancer Research Program, Department of Defense (USA, 2012)
Science and Technology Blasker Award, San Diego Foundation (USA, 2011)
Young Investigator Award, Japan Society of Drug Delivery System (Japan, 2011)
Travel Award - International Symposium, Japan Surgical Society (Japan, 2011)
Young Investigator Award, Japanese Association for Metastasis Research (Japan, 2006)
Best Presentation Awards, Japanese Association for Metastasis Research (Japan, 2003, 2005)
Miyamura N, Yamazaki C, Tsuchikama K, Sugahara KN. Tumor-specific activation of a tissue-penetrating prodrug for enhanced immune-oncotherapy. In preparation.
de Mendoza TH, Mose E, Botta GP, Braun GB, French RP, Ruoslahti E, Lowy A, Sugahara KN. Integrindependent tissue-penetrative targeting of desmoplastic cancer. In preparation.
Liu X, Braun GB, Qin M, Ruoslahti E, Sugahara KN. Tumor-specific in vivo imaging with etchable nanoprobes. Nat Commun 8:343 (2017).
Toome K, Willmore AA, Paiste P, Tobi A, Sugahara KN, Kirsimae K, Ruoslahti E, Braun GB, Teesalu T. Ratiometric in vivo auditioning of targeted silver nanoparticles. Nanoscale 9:10094-100 (2017).
Hunt H, Simon-Gracia L, Tobi A, Kotamraju VR, Sharma S, Nigul M, Sugahara KN, Ruoslahti E, Teesalu T. Targeting of p32 in peritoneal carcinomatosis with intraperitoneal linTT1 peptide-guided pro-apoptotic nanoparticles. J Control Release 260:142-53 (2017).
Ikemoto H, Lingasamy P, Anton Willmore AM, Hunt H, Kurm K, Tammik O, Scodeller P, Simon-Gracia L, Kotamraju VR, Lowy AM, Sugahara KN, Teesalu T. Hyaluronan-binding peptide for targeting peritoneal carcinomatosis. Tumour Biol 39:1010428317701628 (2017).
Simon-Gracia L, Hunt H, Scodeller PD, Gaitzsch J, Kotamraju VR, Sugahara KN, Tammik O, Ruoslahti E, Battaglia G, Teesalu T. iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes. Biomaterials 104:247-57 (2016).
Braun GB, Sugahara KN, Yu OM, Kotamraju VR, Lowy AM, Ruoslahti E, Teesalu T. Urokinase-controlled tumor penetrating peptide. J Control Release 232:188-95 (2016).
Paasonen L, Sharma S, Braun GB, Kotamraju VR, She Z, Sugahara KN, Yliperttula M, Wu B, Pellecchia M, Ruoslahti, Teesalu T. New p32/gC1qR ligands for targeted tumor drug delivery. Chembiochem 17:570-5 (2016).
Willmore AM, Simon-Garcia L, Toome K, Kotamraju VR, Molder T, Sugahara KN, Ruoslahti E, Braun GB, Teesalu T. Targeted silver nanoparticles for ratiometric cellular phenotyping. Nanoscale 8:9096-101 (2016).
Liu X, Braun GB, Zhong H, Hall DJ, Han W, Qin M, Zhao C, Wang M, She ZG, Cao C, Sailor MJ, Stallcup WB, Ruoslahti E, Sugahara KN. Tumor-targeted multimodal optical imaging with versatile cadmium-free quantum dots. Adv Funct Mater 26:267-76 (2016).
Sugahara KN†, Scodeller P, Braun GB, de Mendoza TH, Yamazaki CM, Kluger MD, Kitayama J, Alvarez E, Howell SB, Teesalu T, Ruoslahti E, Lowy AM. A tumor-penetrating peptide enhances circulationindependent targeting of peritoneal carcinomatosis. J Control Release 212:59-69 (2015). (†Correspondence)
Hamilton AM, Aidoudi-Ahmed S, Sharma S, Kotamraju VR, Foster PJ, Sugahara KN, Ruoslahti E, Rutt BK. Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental breast cancer metastasis in the brain. J Mol Med 93:991-1001 (2015).
Sugahara KN†, Braun GB, de Mendoza TH, Kotamraju VR, French R, Lowy AM, Teesalu T, Ruoslahti E. Tumor-penetrating iRGD peptide inhibits metastasis. Mol Cancer Ther 14:120-8 (2015). (†Correspondence).
Pang HB, Braun GB, Friman T, Aza-Blanc P, Ruidiaz M, Sugahara KN, Teesalu T, Ruoslahti E. An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability. Nat Commun 5:4904 (2014).
Braun GB, Friman T, Pang HB, Pallaoro A, de Mendoza TH, Willmore AMA, Kotamraju VR, Sugahara KN, Reich NO, Teesalu T, Ruoslahti E. Etchable plasmonic nanoparticle probes for cell biology. Nat Mater 13:904-11 (2014).
Pang HB, Braun GB, She ZG, Kotamraju VR, Sugahara KN, Teesalu T, Ruoslahti E. A free cysteine prolongs the half-life of a homing peptide and improves its tumor-penetrating activity. J Control Release 175C:48-53 (2013).
Sharma G, Karmali PP, Sugahara KN, Xie H, Kotamraju VR, Ruoslahti E, Smith JW. Depletion of tumorassociated macrophages with clodronate-loaded PLGA nanoparticles. Nano LIFE, 03:04 (2013).
Teesalu T, Sugahara KN, Ruoslahti E. Tumor penetrating peptides. Fron Oncology 3:216 (2013) - invited review article
Agemy L, Kotamraju VR, Friedmann-Morvinski D, Sharma S, Sugahara KN, Ruoslahti E. Proapoptotic peptide-mediated cancer therapy targeted to cell surface p32. Mol Ther 21:2195-204 (2013).
Sanchez-Martin D, Martinez-Torrecuadrada J, Teesalu T, Sugahara KN, Alvarez-Cienfuegos A, Ximenez-Embun P, Fernandez-Perianez R, Martin MT, Molina-Privado I, Ruppen-Canas I, Blanco-Toribio A, Canamero M, Cuesta AM, Compte M, Kremer L, Bellas C, Alonso-Camino V, Guijarro-Munoz I, Sanz L, Ruoslahti E, Alvarez-Vallina L. Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies. Proc Natl Acad Sci USA 110:13791-6 (2013).
Zanuy D, Kotla R, Nussinov R, Teesalu T, Sugahara KN, Aleman C, Haspel N. Sequence dependence of C-end rule peptides in binding and activation of neuropilin-1 receptor. J Struct Biol 182:78-86 (2013).
Chen R, Braun GB, Luo X, Sugahara KN, Teesalu T, Ruoslahti E. Application of a proapoptotic peptide for an intratumoral-spreading cancer therapy. Cancer Res 73:1352-61 (2013).
Alberici L, Roth L, Sugahara KN, Agemy L, Kotamraju VR, Teesalu T, Bordignon C, Traversari C, Rizzardi GP, Ruoslahti E. De novo design of a tumor-penetrating peptide. Cancer Res 73:804-12 (2013).
Roth L, Agemy L, Kotamraju VR, Braun G, Teesalu T, Sugahara KN, Hamzah J, Ruoslahti E. Transtumoral targeting enabled by a novel neuropilin-binding peptide. Oncogene 31:3754-63 (2012).
Teesalu T*†, Sugahara KN*†, Ruoslahti E†. Mapping of vascular zip codes by phage display. Methods Enzymol 503:35-56 (2012). (*Equal contribution, †Correspondence) - invited review article
Agemy L, Friedmann-Morvinski D, Kotamraju VR, Roth L, Sugahara KN, Girard OM, Mattrey RF, Verma IM, Ruoslahti E. Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma. Proc Natl Acad Sci USA 108:17450-5 (2011). Featured in… Proc Natl Acad Sci USA 108:17238 (2011).
Wang J, Liu Y, Teesalu T, Sugahara KN, Adams JD, Ruoslahti E, Xiao Y, Soh HT, Selection of phagedisplayed peptides on live adherent cells in microfluidic channels. Proc Natl Acad Sci USA 108:6909-14 (2011).
Girard OM, Du J, Agemy L, Sugahara KN, Kotamraju VR, Ruoslahti E, Bydder GM, Mattrey RF. Optimization of Iron Oxide Nanoparticle Detection Using Ultrashort TE Pulse Sequences: Comparison of T1, T2* and Synergistic T1-T2* Contrast Mechanisms. Magn Reson Med 65:1649-60 (2011).
Agemy L, Sugahara KN, Kotamraju VR, Gujraty K, Girard OM, Kono Y, Mattrey RF, Park J, Sailor MJ, Jimenez AI, Cativiela C, Zanuy D, Sayago FJ, Aleman C, Nussinov R, Ruoslahti E. Nanoparticle-induced vascular blockade in prostate cancer. Blood 116:2847-56 (2010).
Sugahara KN*, Teesalu T*, Karmali PP, Kotamraju VR, Agemy L, Greenwald RD, Ruoslahti E. Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science 328:1031-5 (2010). (*Equal contribution) Featured in… Science (Vol. 328; Issue 5981, cover article); Nat Rev Cancer 10:384-5 (2010); Nat Rev Drug Discov 9:434 (2010); Nat Biotechnol 28:566 (2010); Sci Transl Med 2:34ps26 (2010); San Diego Union Tribune (4/9/2010 front-page article); Santa Barbara News Press (4/10/2010)
Sugahara KN*, Teesalu T*, Karmali PP, Kotamraju VR, Agemy L, Girard OM, Hanahan D, Mattrey RF, Ruoslahti E. Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell, 16:510-520 (2009). (*Equal contribution) Featured in… Nature 462:700 (2009); Nat Rev Drug Discov 9:106 (2010); Pigment Cell Melanoma Res 23:157-9 (2010); Santa Barbara News Press (12/9/2009); Santa Barbara Independent (1/26/ 2010)
Teesalu T*, Sugahara KN*, Kotamraju VR, Ruoslahti E. C-end Rule: Peptides with C-terminal arginine mediate neuropilin-1 dependent cell, vascular and tissue penetration. Proc Natl Acad Sci USA 106:16157-62 (2009). (*Equal contribution) Featured in… Pigment Cell Melanoma Res 23:157-9 (2010)
Basappa, Murugan S, Sugahara KN, Lee CM, ten Dam GB, van Kuppevelt TH, Miyasaka M, Yamada S, Sugahara K. Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells. Glycobiology 19:735-42 (2009).
Fogal V, Sugahara KN, Ruoslahti E, Christian S. Cell surface nucleolin antagonist causes endothelial cell apoptosis and normalization of tumor vasculature. Angiogenesis 12:91-100 (2009).
Sugahara KN, Hirata T, Tanaka T, Ogino S, Takeda M, Terasawa H, Shimada I, Tamura J, ten Dam GB, van Kuppevelt TH, Miyasaka M. Chondroitin sulfate E fragments enhance CD44 cleavage and CD44-dependent motility in tumor cells. Cancer Res 68:7191-9 (2008). Featured in… Nat Rev Cancer, 8:828 (2008); Nature Functional Glycomics Gateway, October (2008)
Takeda M, Ogino S, Umemoto R, Sakakura M, Kajiwara M, Sugahara KN, Hayasaka H, Miyasaka M, Terasawa H, Shimada I. Ligand-induced structural changes of the CD44 hyaluronan-binding domain revealed by NMR. J Biol Chem 281:40089-95 (2006).
Stern R, Asari A, Sugahara KN. Hyaluronan oligosaccharides: an information-rich system. European J Cell Biol 85:699-715 (2006).
Sugahara KN, Hirata T, Hayasaka H, Stern R, Murai T, Miyasaki M. Tumor cells enhance their own CD44 cleavage and motility by generating hyaluronan fragments. J Biol Chem 281:5861-8 (2006).
Murai T, Miyazaki Y, Nishinakamura H, Sugahara KN, Miyauchi T, Sako Y, Yanagida T, Miyasaka M. Engagement of CD44 promotes Rac activation and CD44 cleavage during tumor cell migration. J Biol Chem 279:4541-50 (2004).
Sugahara KN†, Hirata T, Murai T, Miyasaka M. Hyaluronan oligosaccharides and tumor progression. Trends Glycosci Glycotechnol 16:pp.171-81 (2004). (†Correspondence) - invited review article
Sugahara KN, Murai T, Nishinakamura H, Kawashima H, Saya H, Miyasaka M. Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. J Biol Chem 278:32259-65 (2003).
Sugahara KN, Nakamura H, Kanai M, Iwata S, Kawai Y, Taki Y, Yodoi J, Takabayashi A. Surgical stress during operation for gastrointestinal cancer increases plasma thioredoxin levels and decreases mitochondrial membrane potential in peripheral blood lymphocytes. Redox Rep 7:165-9 (2002).
Sugahara KN, Nakamura H, Iwata S, Kanai M, Denno R, Taki R, Yodoi J, Takabayashi A. The effects of surgical stress during operation for gastrointestinal cancer on mitochondrial membrane potential in peripheral blood lymphocytes and plasma thioredoxin levels. Digestive Organ Immunol 37:28-30 (2000).