Nature Medicine Classic Collection

Welcome to the content sampler of Nature Medicine.

Since 1995, our journal has been at the forefront of publishing translational medicine, way before the term was even coined. Our focus on publishing basic and preclinical work that has direct relevance to human disease has been a key characteristic of Nature Medicine that has helped establish the reputation of the journal in the translational research landscape.

To put together this sampler, we have chosen a series of recent articles from our pages, organized them by therapeutic area, and made them freely available in order to give you a glimpse of the breadth of Nature Medicine's coverage, as well as the quality of the science we publish.

In addition, we have chosen a few landmark articles that we had the privilege to publish over the past 15 years in an effort to illustrate why Nature Medicine is the "Home of Translational Research".


Classic Articles

April 1996

Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations

Marybeth Howard, Raymond A. Frizzell & David M. Bedwell

Nature Medicine 2, 467 - 469 (1996)

Codon skipping using antibiotics is now a mainstream idea that was first shown in this study

May 1996

Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells

Brian J. Druker, Shu Tamura, Elisabeth Buchdunger, Sayuri Ohno, Gerald M. Segal, Shane Fanning, Jürg Zimmermann & Nicholas B. Lydon

Nature Medicine 2, 561 - 566 (1996)

Proof of principle that Bcr-Abl could be targeted in leukemia cells, a crucial finding that led to the development of Gleevec

July 1997

Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell

Dominique Bonnet & John E. Dick

Nature Medicine 3, 730 - 737 (1997)

The discovery of cancer stem cells, several years before they were found in solid tumors

July 1997

Identification of tissue transglutaminase as the autoantigen of celiac disease

Walburga Dieterich, Tobias Ehnis, Michael Bauer, Peter Donner, Umberto Volta, Ernst Otto Riecken & Detlef Schuppan

Nature Medicine 3, 797 - 801 (1997)

The identification of the pathogenic antigen in celiac disease

November 1998

Neurogenesis in the adult human hippocampus

Peter S. Eriksson, Ekaterina Perfilieva, Thomas Björk-Eriksson, Ann-Marie Alborn, Claes Nordborg, Daniel A. Peterson & Fred H. Gage

Nature Medicine 4, 1313 - 1317 (1998)

The first evidence of the birth of new neurons in the human brain

December 2003

Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation

Kenyatta Cosby, Kristine S Partovi, Jack H Crawford, Rakesh P Patel, Christopher D Reiter, Sabrina Martyr, Benjamin K Yang, Myron A Waclawiw, Gloria Zalos, Xiuli Xu, Kris T Huang, Howard Shields, Daniel B Kim-Shapiro, Alan N Schechter, Richard O Cannon III & Mark T Gladwin

Nature Medicine 9, 1498 - 1505 (2003)

An important paper in changing our views about nitric oxide function

August 2006

Cardiotoxicity of the cancer therapeutic agent imatinib mesylate

Risto Kerkelä, Luanda Grazette, Rinat Yacobi, Cezar Iliescu, Richard Patten, Cara Beahm, Brian Walters, Sergei Shevtsov, Stéphanie Pesant, Fred J Clubb, Anthony Rosenzweig, Robert N Salomon, Richard A Van Etten, Joseph Alroy, Jean-Bernard Durand & Thomas Force

Nature Medicine 12, 908 - 916 (2006)

First study to raise the issue of the toxic effects of clinically relevant protein kinase inhibitors on the heart



Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis

Sunny Y Wong, Allen D Seol, Po-Lin So, Alexandre N Ermilov, Christopher K Bichakjian, Ervin H Epstein Jr, Andrzej A Dlugosz & Jeremy F Reiter

Nature Medicine 15, 1055 - 1061 (2009)

Dual and opposing roles of primary cilia in medulloblastoma development

Young-Goo Han, Hong Joo Kim, Andrzej A Dlugosz, David W Ellison, Richard J Gilbertson & Arturo Alvarez-Buylla

Nature Medicine 15, 1062 - 1065 (2009)

These two studies show that primary cilia can either mediate or suppress tumorigenesis in models of basal cell carcinoma and medulloblastoma, respectively, depending on the nature of the initial oncogenic event

Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers

Elgene Lim, François Vaillant, Di Wu, Natasha C Forrest, Bhupinder Pal, Adam H Hart, Marie-Liesse Asselin-Labat, David E Gyorki, Teresa Ward, Audrey Partanen, Frank Feleppa, Lily I Huschtscha, Heather J Thorne, kConFab, Stephen B Fox, Max Yan, Juliet D French, Melissa A Brown, Gordon K Smyth, Jane E Visvader & Geoffrey J Lindeman

Nature Medicine 15, 907 - 913 (2009)

Contrary to the belief that basal-like breast cancers develop from mammary stem cells in BRCA1 mutation carriers, an aberrant luminal progenitor population might be the target for transformation in basal tumors in these individuals

A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma

Hayriye V Erkizan, Yali Kong, Melinda Merchant, Silke Schlottmann, Julie S Barber-Rotenberg, Linshan Yuan, Ogan D Abaan, Tsu-hang Chou, Sivanesan Dakshanamurthy, Milton L Brown, Aykut Üren & Jeffrey A Toretsky

Nature Medicine 15, 750 - 756 (2009)

Ewing's sarcomas often depend on the oncogenic fusion protein EWS-FLI1, which interacts with RNA helicase A (RHA) in transcriptional complexes. This study reports on a small molecule that inhibits the interaction of RHA with EWS-FLI1 and impairs the growth of Ewing's sarcoma xenografts in mice, providing evidence that targeting tumor-specific transcription factors may be a feasible approach to treating cancer


Cardiovascular Disease

Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth

Romulo J C Albuquerque, Takahiko Hayashi, Won Gil Cho, Mark E Kleinman, Sami Dridi, Atsunobu Takeda, Judit Z Baffi, Kiyoshi Yamada, Hiroki Kaneko, Martha G Green, Joe Chappell, Jörg Wilting, Herbert A Weich, Satoru Yamagami, Shiro Amano, Nobuhisa Mizuki, Jonathan S Alexander, Martha L Peterson, Rolf A Brekken, Masanori Hirashima, Seema Capoor, Tomohiko Usui, Balamurali K Ambati & Jayakrishna Ambati

Nature Medicine 15, 1023-1030 (2009)

Although endogenous inhibitors of blood vessel growth have been studied extensively, specific inhibitors of lymphatic vessel growth have not been identified. This study reports on the identification of truncated, secreted versions of mouse and human VEGFR-2 receptors generated by alternative splicing. The mouse protein acts as an endogenous inhibitor of lymphatic vessel growth in the cornea and skin, and its administration had therapeutic effects in mouse models of corneal injury and transplantation

Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II-induced aortic aneurysms

Kimio Satoh, Patrizia Nigro, Tetsuya Matoba, Michael R O'Dell, Zhaoqiang Cui, Xi Shi, Amy Mohan, Chen Yan, Jun-ichi Abe, Karl A Illig & Bradford C Berk

Nature Medicine 15, 649-656 (2009)

The pathogenesis of aortic aneurysms involves inflammatory cell recruitment and increased levels of reactive oxygen species and matrix metalloproteases. This study mechanistically links the protein cyclophilin A-expressed in vascular smooth muscle cells-to these known mediators of aortic aneurysm formation and provide evidence in both mice and humans for the importance of cyclophilin A in aortic aneurysm formation

Biomechanical regulation of blood vessel growth during tissue vascularization

Witold W Kilarski, Branka Samolov, Ludvig Petersson, Anders Kvanta & Pär Gerwins

Nature Medicine 15, 657-664 (2009)

This report shows that the rapid formation of new vessels in healing wound tissue does not depend on endothelial cell proliferation and sprouting, which typically have been presumed to be needed for the growth of new blood vessels. Instead, preexisting vessels enlarge and translocate, a process driven by the tension generated by contracting fibroblasts and/or myofibroblasts

A shear gradient-dependent platelet aggregation mechanism drives thrombus formation

Warwick S Nesbitt, Erik Westein, Francisco Javier Tovar-Lopez, Elham Tolouei, Arnan Mitchell, Jia Fu, Josie Carberry, Andreas Fouras & Shaun P Jackson

Nature Medicine 15, 665-673 (2009)

This report describes a new mechanistic model for thrombus growth within a blood vessel, providing evidence that blood flow shear gradients-which can arise from vessel injury, stenosis or obstruction-are important in driving thrombus formation. Rapid changes in blood shear rates lead to dynamic restructuring of membranous structures, called 'tethers', on the platelet surface, facilitating stable platelet deposition onto a growing thrombus



Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates

Tim A Weaver, Ali H Charafeddine, Avinash Agarwal, Alexandra P Turner, Maria Russell, Frank V Leopardi, Robert L Kampen, Linda Stempora, Mingqing Song, Christian P Larsen & Allan D Kirk

Nature Medicine 15, 746-749 (2009)

Immunosuppressive regimens used to prevent rejection of transplanted organs are associated with many adverse side effects. This report shows that combining the use of a CD2-targeting reagent (alefacept) with a co-stimulation blockade-based protocol can prolong survival of kidney allografts in macaques while avoiding the use of standard immunosuppressive agents

Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease

Kim Midwood, Sandra Sacre, Anna M Piccinini, Julia Inglis, Annette Trebaul, Emma Chan, Stefan Drexler, Nidhi Sofat, Masahide Kashiwagi, Gertraud Orend, Fionula Brennan & Brian Foxwell

Nature Medicine 15, 774-780 (2009)

TLR4 has a key role in driving inflammation in mouse models of arthritis and may also have a role in the human disease. The extracellular matrix protein tenascin-C is upregulated in the joints of individuals with rheumatoid arthritis. This article shows that tenascin-C is an endogenous activator of TLR4 and that it contributes to the maintenance of arthritis in mice

Netting neutrophils in autoimmune small-vessel vasculitis

Kai Kessenbrock, Markus Krumbholz, Ulf Schönermarck, Walter Back, Wolfgang L Gross, Zena Werb, Hermann-Josef Gröne, Volker Brinkmann & Dieter E Jenne

Nature Medicine 15, 623 - 625 (2009)

Neutrophils release neutrophil extracellular traps (NETs), chromatin fibers that can ensnare bacteria. In small-vessel vasculitis (SVV), a chronic inflammatory condition linked to antineutrophil autoantibodies, these NETs express SVV-associated autoantigens, accumulate in inflamed kidneys and promote the autoimmune response against neutrophils in people with SVV

Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies

Marc Pellegrini, Thomas Calzascia, Alisha R Elford, Arda Shahinian, Amy E Lin, Dilan Dissanayake, Salim Dhanji, Linh T Nguyen, Matthew A Gronski, Michel Morre, Brigitte Assouline, Katharina Lahl, Tim Sparwasser, Pamela S Ohashi & Tak W Mak

Nature Medicine 15, 528 - 536 (2009)

Interleukin-7 (IL-7) promotes immune responses and has been touted as a potential tool for improving immune targeting of tumors. This study investigates the mechanisms by which IL-7 increases antitumor responses and the treatment strategies necessary to optimize its effects


Infectious Diseases

CD4 downregulation by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection

Coreen M Beaumier, Levelle D Harris, Simoy Goldstein, Nichole R Klatt, Sonya Whitted, John McGinty, Cristian Apetrei, Ivona Pandrea, Vanessa M Hirsch & Jason M Brenchley

Nature Medicine 15, 879 - 885 (2009)

Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques

Ann J Hessell, Pascal Poignard, Meredith Hunter, Lars Hangartner, David M Tehrani, Wim K Bleeker, Paul W H I Parren, Preston A Marx & Dennis R Burton

Nature Medicine 15, 951 - 954 (2009)

Studies in macaques have shown that neutralizing antibodies can offer robust protection from infection with a simian counterpart of HIV, yet these studies have also suggested that high concentrations of antibodies are required for efficient protection. However, eliciting such high neutralizing antibody titers by vaccination may not be possible. This study shows that lower concentrations of antibodies can offer protection to macaques if a repeated low-dose challenge model is used-a model that may better recapitulate the acquisition of infection in humans

Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71

Yorihiro Nishimura, Masayuki Shimojima, Yoshio Tano, Tatsuo Miyamura, Takaji Wakita & Hiroyuki Shimizu

Nature Medicine 15, 794 - 797 (2009)

Scavenger receptor B2 is a cellular receptor for enterovirus 71

Seiya Yamayoshi, Yasuko Yamashita, Jifen Li, Nobutaka Hanagata, Takashi Minowa, Taro Takemura & Satoshi Koike

Nature Medicine 15, 798 - 801 (2009)

Enterovirus 71 causes hand, foot and mouth disease, a mild infectious disease that can, however, lead to severe neurological impairments. These studies identify two receptors for the virus-P-selectin glycoprotein ligand-1 (PSGL-1) and scavenger receptor class B, member 2 (SCARB2)



A crucial role for adipose tissue p53 in the regulation of insulin resistance

Tohru Minamino, Masayuki Orimo, Ippei Shimizu, Takeshige Kunieda, Masataka Yokoyama, Takashi Ito, Aika Nojima, Akira Nabetani, Yuichi Oike, Hisahiro Matsubara, Fuyuki Ishikawa & Issei Komuro

Nature Medicine 15, 1082-1087 (2009)

A role for cell senescence and the tumor suppressor p53 in the development of insulin resistance (or prediabetes) has been obscure. This report shows that premature cell senescence occurs in the adipose tissue of obese mice and humans and that genetic deficiency of p53 is sufficient to prevent insulin resistance in mouse models of obesity, suggesting a new target to treat diabetes

Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice

Jian Liu, Adeline Divoux, Jiusong Sun, Jie Zhang, Karine Clèment, Jonathan N Glickman, Galina K Sukhova, Paul J Wolters, Juan Du, Cem Z Gorgun, Alessandro Doria, Peter Libby, Richard S Blumberg, Barbara B Kahn, Gökhan S Hotamisligil & Guo-Ping Shi

Nature Medicine 15, 940-945 (2009)

Mast cells, which are involved in inflammation and wound healing, have a role in obesity and diabetes, according to this report. Pharmacological inhibition of mast cell function reduces metabolic disturbances in mice, suggesting a new therapeutic avenue for these disorders

GOAT links dietary lipids with the endocrine control of energy balance

Henriette Kirchner, Jesus A Gutierrez, Patricia J Solenberg, Paul T Pfluger, Traci A Czyzyk, Jill A Willency, Annette Schürmann, Hans-Georg Joost, Ronald J Jandacek, John E Hale, Mark L Heiman & Matthias H Tschöp

Nature Medicine 15, 741 - 745 (2009)

It has been a long-held belief that the hormone ghrelin is activated when an animal is hungry, inducing the brain to increase food intake. This study shows that it is not the deficiency of calories per se that activates ghrelin, but the presence of energy-rich medium-chain dietary fats

Impaired gastric acidification negatively affects calcium homeostasis and bone mass

Thorsten Schinke, Arndt F Schilling, Anke Baranowsky, Sebastian Seitz, Robert P Marshall, Tilman Linn, Michael Blaeker, Antje K Huebner, Ansgar Schulz, Ronald Simon, Matthias Gebauer, Matthias Priemel, Uwe Kornak, Sandra Perkovic, Florian Barvencik, F Timo Beil, Andrea Del Fattore, Annalisa Frattini, Thomas Streichert, Klaus Pueschel, Anna Villa, Klaus-Michael Debatin, Johannes M Rueger, Anna Teti, Jozef Zustin, Guido Sauter & Michael Amling

Nature Medicine 15, 674 - 681 (2009)

Proper calcium levels are needed to maintain healthy bones. This article reports that gastric acidification is a key part of in this process. These findings have important clinical implications for patients with osteoporosis and/or those on proton-pump inhibitors, as well as those with a rare genetic disease that causes excess bone mass



Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery

Muge Yemisci, Yasemin Gursoy-Ozdemir, Atay Vural, Alp Can, Kamil Topalkara & Turgay Dalkara

Nature Medicine 15, 1031 - 1037 (2009)

Ischemia causes pericytes on brain microvessels to contract, obstructing erythrocyte transit even after blood flow is restored. This contraction, which depends on the production of oxygen and nitrogen radicals, represents a novel pathophysiological mechanism in stroke

Pivotal role of cerebral interleukin-17-producing bold gamma delta T cells in the delayed phase of ischemic brain injury

Takashi Shichita, Yuki Sugiyama, Hiroaki Ooboshi, Hiroshi Sugimori, Ryusuke Nakagawa, Ichiro Takada, Toru Iwaki, Yasunori Okada, Mitsuo Iida, Daniel J Cua, Yoichiro Iwakura & Akihiko Yoshimura

Nature Medicine 15, 946 - 950 (2009)

Inflammatory cells invade the brain after stroke, but their role in disease has been unclear. This paper reports that a particular population of T cells that express the inflammatory cytokine IL-17 plays a key role in stroke progression: depletion of these cells-even as late as 1 day after stroke-can alleviate brain injury in mice

Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis

Gurumoorthy Krishnamoorthy, Amit Saxena, Lennart T Mars, Helena S Domingues, Reinhard Mentele, Avraham Ben-Nun, Hans Lassmann, Klaus Dornmair, Florian C Kurschus, Roland S Liblau & Hartmut Wekerle

Nature Medicine 15, 626 - 632 (2009)

T-cell recognition of autoantigens is important in the development of autoimmune disease. This report shows that organ-specific autoimmune responses may be driven by T cells that simultaneously respond to two different autoantigens found within the same target tissue

A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia

Stephen J Huffaker, Jingshan Chen, Kristin K Nicodemus, Fabio Sambataro, Feng Yang, Venkata Mattay, Barbara K Lipska, Thomas M Hyde, Jian Song, Dan Rujescu, Ina Giegling, Karine Mayilyan, Morgan J Proust, Armen Soghoyan, Grazia Caforio, Joseph H Callicott, Alessandro Bertolino, Andreas Meyer-Lindenberg, Jay Chang, Yuanyuan Ji, Michael F Egan, Terry E Goldberg, Joel E Kleinman, Bai Lu & Daniel R Weinberger

Nature Medicine 15, 509 - 518 (2009)

Polymorphisms in a primate-specific isoform of K+ channel KCNH2 are associated with schizophrenia. This isoform induces a rapidly deactivating K+ current and high-frequency neuronal firing pattern. The disease-associated alleles predict lower intelligence quotient scores, lower speed of cognitive processing and altered memory. This channel isoform represents a potential new drug target for psychotherapy

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