Latest Research

  • Letter |

    A pick-the-winner clinical trial design in patients with metastatic triple-negative breast cancer shows that immune induction with doxorubicin or cisplatin may improve clinical responses to PD-1 blockade and induce a more favorable tumor microenvironment.

    • Leonie Voorwerk
    • , Maarten Slagter
    • , Hugo M. Horlings
    • , Karolina Sikorska
    • , Koen K. van de Vijver
    • , Michiel de Maaker
    • , Iris Nederlof
    • , Roelof J. C. Kluin
    • , Sarah Warren
    • , SuFey Ong
    • , Terry G. Wiersma
    • , Nicola S. Russell
    • , Ferry Lalezari
    • , Philip C. Schouten
    • , Noor A. M. Bakker
    • , Steven L. C. Ketelaars
    • , Dennis Peters
    • , Charlotte A. H. Lange
    • , Erik van Werkhoven
    • , Harm van Tinteren
    • , Ingrid A. M. Mandjes
    • , Inge Kemper
    • , Suzanne Onderwater
    • , Myriam Chalabi
    • , Sofie Wilgenhof
    • , John B. A. G. Haanen
    • , Roberto Salgado
    • , Karin E. de Visser
    • , Gabe S. Sonke
    • , Lodewyk F. A. Wessels
    • , Sabine C. Linn
    • , Ton N. Schumacher
    • , Christian U. Blank
    •  & Marleen Kok
  • Article |

    The detrimental effects of aged blood on cognition and nervous system function in mice can be combatted by targeting brain endothelial cell dysfunction via inhibition of aberrant VCAM1 signaling at the blood–brain barrier.

    • Hanadie Yousef
    • , Cathrin J. Czupalla
    • , Davis Lee
    • , Michelle B. Chen
    • , Ashley N. Burke
    • , Kristy A. Zera
    • , Judith Zandstra
    • , Elisabeth Berber
    • , Benoit Lehallier
    • , Vidhu Mathur
    • , Ramesh V. Nair
    • , Liana N. Bonanno
    • , Andrew C. Yang
    • , Todd Peterson
    • , Husein Hadeiba
    • , Taylor Merkel
    • , Jakob Körbelin
    • , Markus Schwaninger
    • , Marion S. Buckwalter
    • , Stephen R. Quake
    • , Eugene C. Butcher
    •  & Tony Wyss-Coray
  • Resource |

    Systematic metabolite profiling across cancer cell lines uncovers patterns associated with genetic and epigenetic features and reveals dysregulated metabolic states that can be exploited for anticancer therapy

    • Haoxin Li
    • , Shaoyang Ning
    • , Mahmoud Ghandi
    • , Gregory V. Kryukov
    • , Shuba Gopal
    • , Amy Deik
    • , Amanda Souza
    • , Kerry Pierce
    • , Paula Keskula
    • , Desiree Hernandez
    • , Julie Ann
    • , Dojna Shkoza
    • , Verena Apfel
    • , Yilong Zou
    • , Francisca Vazquez
    • , Jordi Barretina
    • , Raymond A. Pagliarini
    • , Giorgio G. Galli
    • , David E. Root
    • , William C. Hahn
    • , Aviad Tsherniak
    • , Marios Giannakis
    • , Stuart L. Schreiber
    • , Clary B. Clish
    • , Levi A. Garraway
    •  & William R. Sellers
  • Article |

    Personalized omics profiling can lead to actionable health discoveries and stimulate lifestyle changes.

    • Sophia Miryam Schüssler-Fiorenza Rose
    • , Kévin Contrepois
    • , Kegan J. Moneghetti
    • , Wenyu Zhou
    • , Tejaswini Mishra
    • , Samson Mataraso
    • , Orit Dagan-Rosenfeld
    • , Ariel B. Ganz
    • , Jessilyn Dunn
    • , Daniel Hornburg
    • , Shannon Rego
    • , Dalia Perelman
    • , Sara Ahadi
    • , M. Reza Sailani
    • , Yanjiao Zhou
    • , Shana R. Leopold
    • , Jieming Chen
    • , Melanie Ashland
    • , Jeffrey W. Christle
    • , Monika Avina
    • , Patricia Limcaoco
    • , Camilo Ruiz
    • , Marilyn Tan
    • , Atul J. Butte
    • , George M. Weinstock
    • , George M. Slavich
    • , Erica Sodergren
    • , Tracey L. McLaughlin
    • , Francois Haddad
    •  & Michael P. Snyder
  • Perspective |

    The use and promotion of probiotics is widespread, but debatable in many cases. Prospective large-scale randomized studies that assess their effectiveness in promoting health and curing disease and take into account personalized responses of discrete human subpopulations will help clarify specific indications in which probiotics may be safe and beneficial.

    • Jotham Suez
    • , Niv Zmora
    • , Eran Segal
    •  & Eran Elinav
  • Article |

    Elevated activity of the methionine cycle is essential for cancer stem cell tumorigenesis and represents a therapeutic vulnerability.

    • Zhenxun Wang
    • , Lian Yee Yip
    • , Jia Hui Jane Lee
    • , Zhengwei Wu
    • , Hui Yi Chew
    • , Pooi Kiat William Chong
    • , Chin Chye Teo
    • , Heather Yin-Kuan Ang
    • , Kai Lay Esther Peh
    • , Ju Yuan
    • , Siming Ma
    • , Li Shi Kimberly Choo
    • , Nurhidayah Basri
    • , Xia Jiang
    • , Qiang Yu
    • , Axel M. Hillmer
    • , Wan Teck Lim
    • , Tony Kiat Hon Lim
    • , Angela Takano
    • , Eng Huat Tan
    • , Daniel Shao Weng Tan
    • , Ying Swan Ho
    • , Bing Lim
    •  & Wai Leong Tam
  • Letter |

    Brain organoids derived from human iPSCs are used to study the effects of hypoxia on early cortical neurodevelopment and identify defects in specific human progenitor populations that likely contribute to encephalopathy of prematurity.

    • Anca M. Pașca
    • , Jin-Young Park
    • , Hyun-Woo Shin
    • , Qihao Qi
    • , Omer Revah
    • , Rebecca Krasnoff
    • , Ruth O’Hara
    • , A. Jeremy Willsey
    • , Theo D. Palmer
    •  & Sergiu P. Pașca
  • Letter |

    GITR agonism can be exploited in combination with checkpoint blockade to overcome immune refractoriness in solid tumors.

    • Roberta Zappasodi
    • , Cynthia Sirard
    • , Yanyun Li
    • , Sadna Budhu
    • , Mohsen Abu-Akeel
    • , Cailian Liu
    • , Xia Yang
    • , Hong Zhong
    • , Walter Newman
    • , Jingjing Qi
    • , Phillip Wong
    • , David Schaer
    • , Henry Koon
    • , Vamsidhar Velcheti
    • , Matthew D. Hellmann
    • , Michael A. Postow
    • , Margaret K. Callahan
    • , Jedd D. Wolchok
    •  & Taha Merghoub
  • Article |

    A robust signature of circulating inflammatory proteins is causally associated with 10-year risk of progression to end-stage renal disease in diabetic patients

    • Monika A. Niewczas
    • , Meda E. Pavkov
    • , Jan Skupien
    • , Adam Smiles
    • , Zaipul I. Md Dom
    • , Jonathan M. Wilson
    • , Jihwan Park
    • , Viji Nair
    • , Andrew Schlafly
    • , Pierre-Jean Saulnier
    • , Eiichiro Satake
    • , Christopher A. Simeone
    • , Hetal Shah
    • , Chengxiang Qiu
    • , Helen C. Looker
    • , Paolo Fiorina
    • , Carl F. Ware
    • , Jennifer K. Sun
    • , Alessandro Doria
    • , Matthias Kretzler
    • , Katalin Susztak
    • , Kevin L. Duffin
    • , Robert G. Nelson
    •  & Andrzej S. Krolewski
  • Letter |

    Fusion proteins in cancers with low mutational burden represent functional neoantigens that elicit T cell activation and mediate responses to immunotherapy.

    • Wei Yang
    • , Ken-Wing Lee
    • , Raghvendra M. Srivastava
    • , Fengshen Kuo
    • , Chirag Krishna
    • , Diego Chowell
    • , Vladimir Makarov
    • , Douglas Hoen
    • , Martin G. Dalin
    • , Leonard Wexler
    • , Ronald Ghossein
    • , Nora Katabi
    • , Zaineb Nadeem
    • , Marc A. Cohen
    • , S. Ken Tian
    • , Nicolas Robine
    • , Kanika Arora
    • , Heather Geiger
    • , Phaedra Agius
    • , Nancy Bouvier
    • , Kety Huberman
    • , Katelynd Vanness
    • , Jonathan J. Havel
    • , Jennifer S. Sims
    • , Robert M. Samstein
    • , Rajarsi Mandal
    • , Justin Tepe
    • , Ian Ganly
    • , Alan L. Ho
    • , Nadeem Riaz
    • , Richard J. Wong
    • , Neerav Shukla
    • , Timothy A. Chan
    •  & Luc G. T. Morris
  • Resource |

    A biobank of ovarian cancer organoids recapitulates the histopathological and molecular hallmarks of patient tumors and provides a resource for preclinical research.

    • Oded Kopper
    • , Chris J. de Witte
    • , Kadi Lõhmussaar
    • , Jose Espejo Valle-Inclan
    • , Nizar Hami
    • , Lennart Kester
    • , Anjali Vanita Balgobind
    • , Jeroen Korving
    • , Natalie Proost
    • , Harry Begthel
    • , Lise M. van Wijk
    • , Sonia Aristín Revilla
    • , Rebecca Theeuwsen
    • , Marieke van de Ven
    • , Markus J. van Roosmalen
    • , Bas Ponsioen
    • , Victor W. H. Ho
    • , Benjamin G. Neel
    • , Tjalling Bosse
    • , Katja N. Gaarenstroom
    • , Harry Vrieling
    • , Maaike P. G. Vreeswijk
    • , Paul J. van Diest
    • , Petronella O. Witteveen
    • , Trudy Jonges
    • , Johannes L. Bos
    • , Alexander van Oudenaarden
    • , Ronald P. Zweemer
    • , Hugo J. G. Snippert
    • , Wigard P. Kloosterman
    •  & Hans Clevers
  • Letter |

    Sequencing of circulating tumor DNA from cancer patients is a cost-efficient approach with turnaround time compatible with clinical practice to inform treatment decision-making in a phase 1 trial setting

    • Dominic G. Rothwell
    • , Mahmood Ayub
    • , Natalie Cook
    • , Fiona Thistlethwaite
    • , Louise Carter
    • , Emma Dean
    • , Nigel Smith
    • , Shaun Villa
    • , Joanne Dransfield
    • , Alexandra Clipson
    • , Daniel White
    • , Kamrun Nessa
    • , Saba Ferdous
    • , Matthew Howell
    • , Avinash Gupta
    • , Bedirhan Kilerci
    • , Sumitra Mohan
    • , Kris Frese
    • , Sakshi Gulati
    • , Crispin Miller
    • , Allan Jordan
    • , Helen Eaton
    • , Nicholas Hickson
    • , Ciara O’Brien
    • , Donna Graham
    • , Claire Kelly
    • , Sreeja Aruketty
    • , Robert Metcalf
    • , Jaseela Chiramel
    • , Nadina Tinsley
    • , Alexander J. Vickers
    • , Roopa Kurup
    • , Hannah Frost
    • , Julie Stevenson
    • , Siobhan Southam
    • , Dónal Landers
    • , Andrew Wallace
    • , Richard Marais
    • , Andrew M. Hughes
    • , Ged Brady
    • , Caroline Dive
    •  & Matthew G. Krebs
  • Letter |

    A prospective clinical study of cancer patients (I-PREDICT) demonstrated the feasibility of matching genomic alterations found in tumors to combined drug treatments.

    • Jason K. Sicklick
    • , Shumei Kato
    • , Ryosuke Okamura
    • , Maria Schwaederle
    • , Michael E. Hahn
    • , Casey B. Williams
    • , Pradip De
    • , Amy Krie
    • , David E. Piccioni
    • , Vincent A. Miller
    • , Jeffrey S. Ross
    • , Adam Benson
    • , Jennifer Webster
    • , Philip J. Stephens
    • , J. Jack Lee
    • , Paul T. Fanta
    • , Scott M. Lippman
    • , Brian Leyland-Jones
    •  & Razelle Kurzrock
  • Letter |

    A new anti-CD19 CAR T cell therapy induces potent antitumor responses without causing severe cytokine-release syndrome or neurotoxicity in patients with lymphoma.

    • Zhitao Ying
    • , Xue F. Huang
    • , Xiaoyu Xiang
    • , Yanling Liu
    • , Xi Kang
    • , Yuqin Song
    • , Xiaokai Guo
    • , Hanzhi Liu
    • , Ning Ding
    • , Tingting Zhang
    • , Panpan Duan
    • , Yufu Lin
    • , Wen Zheng
    • , Xiaopei Wang
    • , Ningjing Lin
    • , Meifeng Tu
    • , Yan Xie
    • , Chen Zhang
    • , Weiping Liu
    • , Lijuan Deng
    • , Shunyu Gao
    • , Lingyan Ping
    • , Xuejuan Wang
    • , Nina Zhou
    • , Junqing Zhang
    • , Yulong Wang
    • , Songfeng Lin
    • , Mierzhati Mamuti
    • , Xueyun Yu
    • , Lizhu Fang
    • , Shuai Wang
    • , Haifeng Song
    • , Guan Wang
    • , Lindsey Jones
    • , Jun Zhu
    •  & Si-Yi Chen
  • Letter |

    Prospective analysis of transcriptomic and genomic alterations increases the proportion of patients with solid cancer who are eligible for receiving matched therapies and shows promise in improving clinical outcomes.

    • Jordi Rodon
    • , Jean-Charles Soria
    • , Raanan Berger
    • , Wilson H. Miller
    • , Eitan Rubin
    • , Aleksandra Kugel
    • , Apostolia Tsimberidou
    • , Pierre Saintigny
    • , Aliza Ackerstein
    • , Irene Braña
    • , Yohann Loriot
    • , Mohammad Afshar
    • , Vincent Miller
    • , Fanny Wunder
    • , Catherine Bresson
    • , Jean-François Martini
    • , Jacques Raynaud
    • , John Mendelsohn
    • , Gerald Batist
    • , Amir Onn
    • , Josep Tabernero
    • , Richard L. Schilsky
    • , Vladimir Lazar
    • , J. Jack Lee
    •  & Razelle Kurzrock
  • Author Correction |

    • Junfei Zhao
    • , Andrew X. Chen
    • , Robyn D. Gartrell
    • , Andrew M. Silverman
    • , Luis Aparicio
    • , Tim Chu
    • , Darius Bordbar
    • , David Shan
    • , Jorge Samanamud
    • , Aayushi Mahajan
    • , Ioan Filip
    • , Rose Orenbuch
    • , Morgan Goetz
    • , Jonathan T. Yamaguchi
    • , Michael Cloney
    • , Craig Horbinski
    • , Rimas V. Lukas
    • , Jeffrey Raizer
    • , Ali I. Rae
    • , Jinzhou Yuan
    • , Peter Canoll
    • , Jeffrey N. Bruce
    • , Yvonne M. Saenger
    • , Peter Sims
    • , Fabio M. Iwamoto
    • , Adam M. Sonabend
    •  & Raul Rabadan
  • Article |

    In situ vaccine recruits and activates cross-presenting dendritic cells and augments PD1 blockade efficacy in patients with indolent non-Hodgkin’s lymphoma.

    • Linda Hammerich
    • , Thomas U. Marron
    • , Ranjan Upadhyay
    • , Judit Svensson-Arvelund
    • , Maxime Dhainaut
    • , Shafinaz Hussein
    • , Yougen Zhan
    • , Dana Ostrowski
    • , Michael Yellin
    • , Henry Marsh
    • , Andres M. Salazar
    • , Adeeb H. Rahman
    • , Brian D. Brown
    • , Miriam Merad
    •  & Joshua D. Brody
  • Article |

    Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma

    • Mohsen Malehmir
    • , Dominik Pfister
    • , Suchira Gallage
    • , Marta Szydlowska
    • , Donato Inverso
    • , Elena Kotsiliti
    • , Valentina Leone
    • , Moritz Peiseler
    • , Bas G. J. Surewaard
    • , Dominik Rath
    • , Adnan Ali
    • , Monika Julia Wolf
    • , Hannah Drescher
    • , Marc E. Healy
    • , Daniel Dauch
    • , Daniela Kroy
    • , Oliver Krenkel
    • , Marlene Kohlhepp
    • , Thomas Engleitner
    • , Alexander Olkus
    • , Tjeerd Sijmonsma
    • , Julia Volz
    • , Carsten Deppermann
    • , David Stegner
    • , Patrick Helbling
    • , César Nombela-Arrieta
    • , Anahita Rafiei
    • , Martina Hinterleitner
    • , Marcel Rall
    • , Florian Baku
    • , Oliver Borst
    • , Caroline L. Wilson
    • , Jack Leslie
    • , Tracy O’Connor
    • , Christopher J. Weston
    • , David H. Adams
    • , Lozan Sheriff
    • , Ana Teijeiro
    • , Marco Prinz
    • , Ruzhica Bogeska
    • , Natasha Anstee
    • , Malte N. Bongers
    • , Mike Notohamiprodjo
    • , Tobias Geisler
    • , Dominic J. Withers
    • , Jerry Ware
    • , Derek A. Mann
    • , Hellmut G. Augustin
    • , Alexandros Vegiopoulos
    • , Michael D. Milsom
    • , Adam J. Rose
    • , Patricia F. Lalor
    • , Josep M. Llovet
    • , Roser Pinyol
    • , Frank Tacke
    • , Roland Rad
    • , Matthias Matter
    • , Nabil Djouder
    • , Paul Kubes
    • , Percy A. Knolle
    • , Kristian Unger
    • , Lars Zender
    • , Bernhard Nieswandt
    • , Meinrad Gawaz
    • , Achim Weber
    •  & Mathias Heikenwalder
  • Article |

    Cross-study analysis defines fecal microbial species associated with colorectal cancer.

    • Jakob Wirbel
    • , Paul Theodor Pyl
    • , Ece Kartal
    • , Konrad Zych
    • , Alireza Kashani
    • , Alessio Milanese
    • , Jonas S. Fleck
    • , Anita Y. Voigt
    • , Albert Palleja
    • , Ruby Ponnudurai
    • , Shinichi Sunagawa
    • , Luis Pedro Coelho
    • , Petra Schrotz-King
    • , Emily Vogtmann
    • , Nina Habermann
    • , Emma Niméus
    • , Andrew M. Thomas
    • , Paolo Manghi
    • , Sara Gandini
    • , Davide Serrano
    • , Sayaka Mizutani
    • , Hirotsugu Shiroma
    • , Satoshi Shiba
    • , Tatsuhiro Shibata
    • , Shinichi Yachida
    • , Takuji Yamada
    • , Levi Waldron
    • , Alessio Naccarati
    • , Nicola Segata
    • , Rashmi Sinha
    • , Cornelia M. Ulrich
    • , Hermann Brenner
    • , Manimozhiyan Arumugam
    • , Peer Bork
    •  & Georg Zeller
  • Article |

    A small molecule that restores the integrity of the intestinal barrier provides a novel therapeutic strategy for inflammatory bowel diseases.

    • W. Vallen Graham
    • , Weiqi He
    • , Amanda M. Marchiando
    • , Juanmin Zha
    • , Gurminder Singh
    • , Hua-Shan Li
    • , Amlan Biswas
    • , Ma. Lora Drizella M. Ong
    • , Zhi-Hui Jiang
    • , Wangsun Choi
    • , Harmon Zuccola
    • , Yitang Wang
    • , James Griffith
    • , Jingshing Wu
    • , Harry J. Rosenberg
    • , Yingmin Wang
    • , Scott B. Snapper
    • , David Ostrov
    • , Stephen C. Meredith
    • , Lawrence W. Miller
    •  & Jerrold R. Turner
  • Article |

    Multicohort analysis identifies microbial signatures of colorectal cancer in fecal microbiomes.

    • Andrew Maltez Thomas
    • , Paolo Manghi
    • , Francesco Asnicar
    • , Edoardo Pasolli
    • , Federica Armanini
    • , Moreno Zolfo
    • , Francesco Beghini
    • , Serena Manara
    • , Nicolai Karcher
    • , Chiara Pozzi
    • , Sara Gandini
    • , Davide Serrano
    • , Sonia Tarallo
    • , Antonio Francavilla
    • , Gaetano Gallo
    • , Mario Trompetto
    • , Giulio Ferrero
    • , Sayaka Mizutani
    • , Hirotsugu Shiroma
    • , Satoshi Shiba
    • , Tatsuhiro Shibata
    • , Shinichi Yachida
    • , Takuji Yamada
    • , Jakob Wirbel
    • , Petra Schrotz-King
    • , Cornelia M. Ulrich
    • , Hermann Brenner
    • , Manimozhiyan Arumugam
    • , Peer Bork
    • , Georg Zeller
    • , Francesca Cordero
    • , Emmanuel Dias-Neto
    • , João Carlos Setubal
    • , Adrian Tett
    • , Barbara Pardini
    • , Maria Rescigno
    • , Levi Waldron
    • , Alessio Naccarati
    •  & Nicola Segata
  • Publisher Correction |

    • Conan G. Kinsey
    • , Soledad A. Camolotto
    • , Amelie M. Boespflug
    • , Katrin P. Guillen
    • , Mona Foth
    • , Amanda Truong
    • , Sophia S. Schuman
    • , Jill E. Shea
    • , Michael T. Seipp
    • , Jeffrey T. Yap
    • , Lance D. Burrell
    • , David H. Lum
    • , Jonathan R. Whisenant
    • , G. Weldon Gilcrease III
    • , Courtney C. Cavalieri
    • , Kaitrin M. Rehbein
    • , Stephanie L. Cutler
    • , Kajsa E. Affolter
    • , Alana L. Welm
    • , Bryan E. Welm
    • , Courtney L. Scaife
    • , Eric L. Snyder
    •  & Martin McMahon
  • Brief Communication |

    Mass cytometry identifies a unique phenotype enriched in CD4+ T cells isolated from autoimmune disease patients.

    • Asbjørn Christophersen
    • , Eivind G. Lund
    • , Omri Snir
    • , Elsa Solà
    • , Chakravarthi Kanduri
    • , Shiva Dahal-Koirala
    • , Stephanie Zühlke
    • , Øyvind Molberg
    • , Paul J. Utz
    • , Mina Rohani-Pichavant
    • , Julia F. Simard
    • , Cornelia L. Dekker
    • , Knut E. A. Lundin
    • , Ludvig M. Sollid
    •  & Mark M. Davis
  • Letter |

    Post-transplantation relapse in acute myeloid leukemia patients without genomic loss of HLA is driven by transcriptional alterations in antigen presentation and T cell costimulation genes.

    • Cristina Toffalori
    • , Laura Zito
    • , Valentina Gambacorta
    • , Michela Riba
    • , Giacomo Oliveira
    • , Gabriele Bucci
    • , Matteo Barcella
    • , Orietta Spinelli
    • , Raffaella Greco
    • , Lara Crucitti
    • , Nicoletta Cieri
    • , Maddalena Noviello
    • , Francesco Manfredi
    • , Elisa Montaldo
    • , Renato Ostuni
    • , Matteo M. Naldini
    • , Bernhard Gentner
    • , Miguel Waterhouse
    • , Robert Zeiser
    • , Jurgen Finke
    • , Maher Hanoun
    • , Dietrich W. Beelen
    • , Ivana Gojo
    • , Leo Luznik
    • , Masahiro Onozawa
    • , Takanori Teshima
    • , Raynier Devillier
    • , Didier Blaise
    • , Constantijn J. M. Halkes
    • , Marieke Griffioen
    • , Matteo G. Carrabba
    • , Massimo Bernardi
    • , Jacopo Peccatori
    • , Cristina Barlassina
    • , Elia Stupka
    • , Dejan Lazarevic
    • , Giovanni Tonon
    • , Alessandro Rambaldi
    • , Davide Cittaro
    • , Chiara Bonini
    • , Katharina Fleischhauer
    • , Fabio Ciceri
    •  & Luca Vago
  • Letter |

    Newborn neurons are continuously incorporated into the healthy adult human hippocampus up to the ninth decade of life. However, robust adult hippocampal neurogenesis sharply declines during the progression of Alzheimer’s disease.

    • Elena P. Moreno-Jiménez
    • , Miguel Flor-García
    • , Julia Terreros-Roncal
    • , Alberto Rábano
    • , Fabio Cafini
    • , Noemí Pallas-Bazarra
    • , Jesús Ávila
    •  & María Llorens-Martín
  • Letter |

    Optimized conditions for ribonucleoprotein delivery of Cas9–sgRNA complexes enables precise and efficient gene editing to restore fetal hemoglobin expression in sickle cell disease patient-derived HSCs

    • Yuxuan Wu
    • , Jing Zeng
    • , Benjamin P. Roscoe
    • , Pengpeng Liu
    • , Qiuming Yao
    • , Cicera R. Lazzarotto
    • , Kendell Clement
    • , Mitchel A. Cole
    • , Kevin Luk
    • , Cristina Baricordi
    • , Anne H. Shen
    • , Chunyan Ren
    • , Erica B. Esrick
    • , John P. Manis
    • , David M. Dorfman
    • , David A. Williams
    • , Alessandra Biffi
    • , Carlo Brugnara
    • , Luca Biasco
    • , Christian Brendel
    • , Luca Pinello
    • , Shengdar Q. Tsai
    • , Scot A. Wolfe
    •  & Daniel E. Bauer
  • Letter |

    A longitudinal survey of maternal antiviral antibodies in newborns provides a blueprint for understanding infectious disease susceptibility and vaccine development, and inform vaccine scheduling in newborn children.

    • Christian Pou
    • , Dieudonné Nkulikiyimfura
    • , Ewa Henckel
    • , Axel Olin
    • , Tadepally Lakshmikanth
    • , Jaromir Mikes
    • , Jun Wang
    • , Yang Chen
    • , Anna Karin Bernhardsson
    • , Anna Gustafsson
    • , Kajsa Bohlin
    •  & Petter Brodin
  • Letter |

    In a nested case-control study from the China Kadoorie Biobank, lowering blood low-density lipoprotein cholesterol levels confers lower risk for ischemic stroke but elevated risk for intracerebral hemorrhage, which was confirmed by genetic Mendelian randomization analyses.

    • Luanluan Sun
    • , Robert Clarke
    • , Derrick Bennett
    • , Yu Guo
    • , Robin G. Walters
    • , Michael Hill
    • , Sarah Parish
    • , Iona Y. Millwood
    • , Zheng Bian
    • , Yiping Chen
    • , Canqing Yu
    • , Jun Lv
    • , Rory Collins
    • , Junshi Chen
    • , Richard Peto
    • , Liming Li
    • , Zhengming Chen
    • , Junshi Chen
    • , Zhengming Chen
    • , Robert Clarke
    • , Rory Collins
    • , Yu Guo
    • , Liming Li
    • , Jun Lv
    • , Richard Peto
    • , Robin Walters
    • , Daniel Avery
    • , Derrick Bennett
    • , Ruth Boxall
    • , Fiona Bragg
    • , Yumei Chang
    • , Yiping Chen
    • , Zhengming Chen
    • , Robert Clarke
    • , Huaidong Du
    • , Simon Gilbert
    • , Alex Hacker
    • , Michael Holmes
    • , Christiana Kartsonaki
    • , Rene Kerosi
    • , Garry Lancaster
    • , Kuang Lin
    • , John McDonnell
    • , Iona Millwood
    • , Qunhua Nie
    • , Jayakrishnan Radhakrishnan
    • , Paul Ryder
    • , Sam Sansome
    • , Dan Schmidt
    • , Rajani Sohoni
    • , Iain Turnbull
    • , Robin Walters
    • , Jenny Wang
    • , Lin Wang
    • , Neil Wright
    • , Ling Yang
    • , Xiaoming Yang
    • , Zheng Bian
    • , Yu Guo
    • , Xiao Han
    • , Can Hou
    • , Biao Jing
    • , Chao Liu
    • , Jun Lv
    • , Pei Pei
    • , Yunlong Tan
    • , Canqing Yu
    • , Zengchang Pang
    • , Ruqin Gao
    • , Shanpeng Li
    • , Shaojie Wang
    • , Yongmei Liu
    • , Ranran Du
    • , Yajing Zang
    • , Liang Cheng
    • , Xiaocao Tian
    • , Hua Zhang
    • , Yaoming Zhai
    • , Feng Ning
    • , Xiaohui Sun
    • , Feifei Li
    • , Silu Lv
    • , Junzheng Wang
    • , Wei Hou
    • , Mingyuan Zeng
    • , Ge Jiang
    • , Xue Zhou
    • , Liqiu Yang
    • , Hui He
    • , Bo Yu
    • , Yanjie Li
    • , Qinai Xu
    • , Quan Kang
    • , Ziyan Guo
    • , Dan Wang
    • , Ximin Hu
    • , Hongmei Wang
    • , Jinyan Chen
    • , Yan Fu
    • , Zhenwang Fu
    • , Xiaohuan Wang
    • , Min Weng
    • , Zhendong Guo
    • , Shukuan Wu
    • , Yilei Li
    • , Huimei Li
    • , Zhifang Fu
    • , Ming Wu
    • , Yonglin Zhou
    • , Jinyi Zhou
    • , Ran Tao
    • , Jie Yang
    • , Jian Su
    • , Fang Liu
    • , Jun Zhang
    • , Yihe Hu
    • , Yan Lu
    • , Liangcai Ma
    • , Aiyu Tang
    • , Shuo Zhang
    • , Jianrong Jin
    • , Jingchao Liu
    • , Zhenzhu Tang
    • , Naying Chen
    • , Ying Huang
    • , Mingqiang Li
    • , Jinhuai Meng
    • , Rong Pan
    • , Qilian Jiang
    • , Jian Lan
    • , Yun Liu
    • , Liuping Wei
    • , Liyuan Zhou
    • , Ningyu Chen
    • , Ping Wang
    • , Fanwen Meng
    • , Yulu Qin
    • , Sisi Wang
    • , Xianping Wu
    • , Ningmei Zhang
    • , Xiaofang Chen
    • , Weiwei Zhou
    • , Guojin Luo
    • , Jianguo Li
    • , Xiaofang Chen
    • , Xunfu Zhong
    • , Jiaqiu Liu
    • , Qiang Sun
    • , Pengfei Ge
    • , Xiaolan Ren
    • , Caixia Dong
    • , Hui Zhang
    • , Enke Mao
    • , Xiaoping Wang
    • , Tao Wang
    • , Xi Zhang
    • , Ding Zhang
    • , Gang Zhou
    • , Shixian Feng
    • , Liang Chang
    • , Lei Fan
    • , Yulian Gao
    • , Tianyou He
    • , Huarong Sun
    • , Pan He
    • , Chen Hu
    • , Xukui Zhang
    • , Huifang Wu
    • , Min Yu
    • , Ruying Hu
    • , Hao Wang
    • , Yijian Qian
    • , Chunmei Wang
    • , Kaixu Xie
    • , Lingli Chen
    • , Yidan Zhang
    • , Dongxia Pan
    • , Qijun Gu
    • , Yuelong Huang
    • , Biyun Chen
    • , Li Yin
    • , Huilin Liu
    • , Zhongxi Fu
    • , Qiaohua Xu
    • , Xin Xu
    • , Hao Zhang
    • , Huajun Long
    • , Xianzhi Li
    • , Libo Zhang
    •  & Zhe Qiu
  • Letter |

    iPSC-derived brain organoids from patients with neurodevelopmental disease reveal dysfunction in neural progenitors underlying impaired migration of developing neurons in periventricular heterotopia.

    • Johannes Klaus
    • , Sabina Kanton
    • , Christina Kyrousi
    • , Ane Cristina Ayo-Martin
    • , Rossella Di Giaimo
    • , Stephan Riesenberg
    • , Adam C. O’Neill
    • , J. Gray Camp
    • , Chiara Tocco
    • , Malgorzata Santel
    • , Ejona Rusha
    • , Micha Drukker
    • , Mariana Schroeder
    • , Magdalena Götz
    • , Stephen P. Robertson
    • , Barbara Treutlein
    •  & Silvia Cappello
  • Publisher Correction |

    • Bahtiyar Yilmaz
    • , Pascal Juillerat
    • , Ove Øyås
    • , Charlotte Ramon
    • , Francisco Damian Bravo
    • , Yannick Franc
    • , Nicolas Fournier
    • , Pierre Michetti
    • , Christoph Mueller
    • , Markus Geuking
    • , Valerie E. H. Pittet
    • , Michel H. Maillard
    • , Gerhard Rogler
    • , Karim Abdelrahman
    • , Gentiana Ademi
    • , Patrick Aepli
    • , Amman Thomas
    • , Claudia Anderegg
    • , Anca-Teodora Antonino
    • , Eva Archanioti
    • , Eviano Arrigoni
    • , Diana Bakker de Jong
    • , Bruno Balsiger
    • , Polat Bastürk
    • , Peter Bauerfeind
    • , Andrea Becocci
    • , Dominique Belli
    • , José M. Bengoa
    • , Luc Biedermann
    • , Janek Binek
    • , Mirjam Blattmann
    • , Stephan Boehm
    • , Tujana Boldanova
    • , Jan Borovicka
    • , Christian P. Braegger
    • , Stephan Brand
    • , Lukas Brügger
    • , Simon Brunner
    • , Patrick Bühr
    • , Bernard Burnand
    • , Sabine Burk
    • , Emanuel Burri
    • , Sophie Buyse
    • , Dahlia-Thao Cao
    • , Ove Carstens
    • , Dominique H. Criblez
    • , Sophie Cunningham
    • , Fabrizia D’Angelo
    • , Philippe de Saussure
    • , Lukas Degen
    • , Joakim Delarive
    • , Christopher Doerig
    • , Barbara Dora
    • , Susan Drerup
    • , Mara Egger
    • , Ali El-Wafa
    • , Matthias Engelmann
    • , Jessica Ezri
    • , Christian Felley
    • , Markus Fliegner
    • , Nicolas Fournier
    • , Montserrat Fraga
    • , Yannick Franc
    • , Pascal Frei
    • , Remus Frei
    • , Michael Fried
    • , Florian Froehlich
    • , Raoul Ivano Furlano
    • , Luca Garzoni
    • , Martin Geyer
    • , Laurent Girard
    • , Marc Girardin
    • , Delphine Golay
    • , Ignaz Good
    • , Ulrike Graf Bigler
    • , Beat Gysi
    • , Johannes Haarer
    • , Marcel Halama
    • , Janine Haldemann
    • , Pius Heer
    • , Benjamin Heimgartner
    • , Beat Helbling
    • , Peter Hengstler
    • , Denise Herzog
    • , Cyrill Hess
    • , Roxane Hessler
    • , Klaas Heyland
    • , Thomas Hinterleitner
    • , Claudia Hirschi
    • , Petr Hruz
    • , Pascal Juillerat
    • , Carolina Khalid-de Bakker
    • , Stephan Kayser
    • , Céline Keller
    • , Christina Knellwolf (-Grieger)
    • , Christoph Knoblauch
    • , Henrik Köhler
    • , Rebekka Koller
    • , Claudia Krieger(-Grübel)
    • , Patrizia Künzler
    • , Rachel Kusche
    • , Frank Serge Lehmann
    • , Andrew J. Macpherson
    • , Michel H. Maillard
    • , Michael Manz
    • , Astrid Marot
    • , Rémy Meier
    • , Christa Meyenberger
    • , Pamela Meyer
    • , Pierre Michetti
    • , Benjamin Misselwitz
    • , Patrick Mosler
    • , Christian Mottet
    • , Christoph Müller
    • , Beat Müllhaupt
    • , Leilla Musso
    • , Michaela Neagu
    • , Cristina Nichita
    • , Jan Niess
    • , Andreas Nydegger
    • , Nicole Obialo
    • , Diana Ollo
    • , Cassandra Oropesa
    • , Ulrich Peter
    • , Daniel Peternac
    • , Laetitia Marie Petit
    • , Valérie Pittet
    • , Daniel Pohl
    • , Marc Porzner
    • , Claudia Preissler
    • , Nadia Raschle
    • , Ronald Rentsch
    • , Alexandre Restellini
    • , Sophie Restellini
    • , Jean-Pierre Richterich
    • , Frederic Ris
    • , Branislav Risti
    • , Marc Alain Ritz
    • , Gerhard Rogler
    • , Nina Röhrich
    • , Jean-Benoît Rossel
    • , Vanessa Rueger
    • , Monica Rusticeanu
    • , Markus Sagmeister
    • , Gaby Saner
    • , Bernhard Sauter
    • , Mikael Sawatzki
    • , Michael Scharl
    • , Martin Schelling
    • , Susanne Schibli
    • , Hugo Schlauri
    • , Dominique Schluckebier
    • , Daniela Schmid
    • , Sybille Schmid (-Uebelhart)
    • , Jean-François Schnegg
    • , Alain Schoepfer
    • , Vivianne Seematter
    • , Frank Seibold
    • , Mariam Seirafi
    • , Gian-Marco Semadeni
    • , Arne Senning
    • , Christiane Sokollik
    • , Joachim Sommer
    • , Johannes Spalinger
    • , Holger Spangenberger
    • , Philippe Stadler
    • , Peter Staub
    • , Dominic Staudenmann
    • , Volker Stenz
    • , Michael Steuerwald
    • , Alex Straumann
    • , Bruno Strebel
    • , Andreas Stulz
    • , Michael Sulz
    • , Aurora Tatu
    • , Michela Tempia-Caliera
    • , Joël Thorens
    • , Kaspar Truninger
    • , Radu Tutuian
    • , Patrick Urfer
    • , Stephan Vavricka
    • , Francesco Viani
    • , Jürg Vögtlin
    • , Roland Von Känel
    • , Dominique Vouillamoz
    • , Rachel Vulliamy
    • , Paul Wiesel
    • , Reiner Wiest
    • , Stefanie Wöhrle
    • , Samuel Zamora
    • , Silvan Zander
    • , Tina Wylie
    • , Jonas Zeitz
    • , Dorothee Zimmermann
    • , Reiner Wiest
    • , Jörg Stelling
    •  & Andrew J. Macpherson
  • Article |

    Defects in the regulation of leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity.

    • Olof S. Dallner
    • , Jill M. Marinis
    • , Yi-Hsueh. Lu
    • , Kivanc Birsoy
    • , Emory Werner
    • , Gulya Fayzikhodjaeva
    • , Brian D. Dill
    • , Henrik Molina
    • , Arden Moscati
    • , Zoltán Kutalik
    • , Pedro Marques-Vidal
    • , Tuomas O. Kilpeläinen
    • , Niels Grarup
    • , Allan Linneberg
    • , Yinxin Zhang
    • , Roger Vaughan
    • , Ruth J. F. Loos
    • , Mitchell A. Lazar
    •  & Jeffrey M. Friedman
  • Review Article |

    The microbiome influences response to cancer therapy, including cancer immunotherapy, and also plays a role in therapeutic toxicity.

    • Beth A. Helmink
    • , M. A. Wadud Khan
    • , Amanda Hermann
    • , Vancheswaran Gopalakrishnan
    •  & Jennifer A. Wargo
  • Article |

    An integrated high-dimensional measurement of immune age describes a person’s immune status better than chronological age and predicts all-cause mortality.

    • Ayelet Alpert
    • , Yishai Pickman
    • , Michael Leipold
    • , Yael Rosenberg-Hasson
    • , Xuhuai Ji
    • , Renaud Gaujoux
    • , Hadas Rabani
    • , Elina Starosvetsky
    • , Ksenya Kveler
    • , Steven Schaffert
    • , David Furman
    • , Oren Caspi
    • , Uri Rosenschein
    • , Purvesh Khatri
    • , Cornelia L. Dekker
    • , Holden T. Maecker
    • , Mark M. Davis
    •  & Shai S. Shen-Orr
  • Letter |

    QPCTL is a modifier of CD47-SIRPα binding and its blockade enhances macrophage- and neutrophil-mediated antibody dependent cellular cytotoxicity towards tumor cells.

    • Meike E. W. Logtenberg
    • , J. H. Marco Jansen
    • , Matthijs Raaben
    • , Mireille Toebes
    • , Katka Franke
    • , Arianne M. Brandsma
    • , Hanke L. Matlung
    • , Astrid Fauster
    • , Raquel Gomez-Eerland
    • , Noor A. M. Bakker
    • , Simone van der Schot
    • , Koen A. Marijt
    • , Martijn Verdoes
    • , John B. A. G. Haanen
    • , Joost H. van den Berg
    • , Jacques Neefjes
    • , Timo K. van den Berg
    • , Thijn R. Brummelkamp
    • , Jeanette H. W. Leusen
    • , Ferenc A. Scheeren
    •  & Ton N. Schumacher
  • Letter |

    Targeted inhibition of RAF–MEK–ERK signaling induces autophagy through the LKB1–AMPK axis, creating a therapeutic vulnerability that can be exploited for treating patients with pancreatic cancer and potentially other RAS-mutant tumors.

    • Conan G. Kinsey
    • , Soledad A. Camolotto
    • , Amelie M. Boespflug
    • , Katrin P. Guillen
    • , Mona Foth
    • , Amanda Truong
    • , Sophia S. Schuman
    • , Jill E. Shea
    • , Michael T. Seipp
    • , Jeffrey T. Yap
    • , Lance D. Burrell
    • , David H. Lum
    • , Jonathan R. Whisenant
    • , G. Weldon Gilcrease III
    • , Courtney C. Cavalieri
    • , Kaitrin M. Rehbein
    • , Stephanie L. Cutler
    • , Kajsa E. Affolter
    • , Alana L. Welm
    • , Bryan E. Welm
    • , Courtney L. Scaife
    • , Eric L. Snyder
    •  & Martin McMahon
  • Letter |

    Rearrangements in MAP3K8 respond to MEK inhibition and represent the most common genetic driver in pediatric spitzoid melanoma, and in some adult melanomas lacking other MAPK alterations and for which clinical testing is warranted.

    • Scott Newman
    • , Liying Fan
    • , Allison Pribnow
    • , Antonina Silkov
    • , Stephen V. Rice
    • , Seungjae Lee
    • , Ying Shao
    • , Bridget Shaner
    • , Heather Mulder
    • , Joy Nakitandwe
    • , Sheila Shurtleff
    • , Elizabeth M. Azzato
    • , Gang Wu
    • , Xin Zhou
    • , Raymond Barnhill
    • , John Easton
    • , Kim E. Nichols
    • , David W. Ellison
    • , James R. Downing
    • , Alberto Pappo
    • , Philip M. Potter
    • , Jinghui Zhang
    •  & Armita Bahrami
  • Article |

    Blockade of ERK signaling in KRAS-mutant pancreatic cancer increases the dependence on autophagic flux through different mechanisms and provides a rationale for combinatorial targeting with autophagy inhibitors.

    • Kirsten L. Bryant
    • , Clint A. Stalnecker
    • , Daniel Zeitouni
    • , Jennifer E. Klomp
    • , Sen Peng
    • , Andrey P. Tikunov
    • , Venugopal Gunda
    • , Mariaelena Pierobon
    • , Andrew M. Waters
    • , Samuel D. George
    • , Garima Tomar
    • , Björn Papke
    • , G. Aaron Hobbs
    • , Liang Yan
    • , Tikvah K. Hayes
    • , J. Nathaniel Diehl
    • , Gennifer D. Goode
    • , Nina V. Chaika
    • , Yingxue Wang
    • , Guo-Fang Zhang
    • , Agnieszka K. Witkiewicz
    • , Erik S. Knudsen
    • , Emanuel F. Petricoin III
    • , Pankaj K. Singh
    • , Jeffrey M. Macdonald
    • , Nhan L. Tran
    • , Costas A. Lyssiotis
    • , Haoqiang Ying
    • , Alec C. Kimmelman
    • , Adrienne D. Cox
    •  & Channing J. Der
  • Article |

    Blockade of sialic acid-binding protein Siglec-15 expressed in cancer and tumor-infiltrating myeloid cells reverses immunesupression and represents a novel target for cancer immunotherapy independent from the PD-1/PD-L1 axis.

    • Jun Wang
    • , Jingwei Sun
    • , Linda N. Liu
    • , Dallas B. Flies
    • , Xinxin Nie
    • , Maria Toki
    • , Jianping Zhang
    • , Chang Song
    • , Melissa Zarr
    • , Xu Zhou
    • , Xue Han
    • , Kristina A. Archer
    • , Thomas O’Neill
    • , Roy S. Herbst
    • , Agedi N. Boto
    • , Miguel F. Sanmamed
    • , Solomon Langermann
    • , David L. Rimm
    •  & Lieping Chen
  • Letter |

    Neoadjuvant PD-1 blockade in patients with resectable melanoma followed by adjuvant maintenance results in early immunological effects driving clinical benefit and reveals transcriptional and genomic mechanisms of response.

    • Alexander C. Huang
    • , Robert J. Orlowski
    • , Xiaowei Xu
    • , Rosemarie Mick
    • , Sangeeth M. George
    • , Patrick K. Yan
    • , Sasikanth Manne
    • , Adam A. Kraya
    • , Bradley Wubbenhorst
    • , Liza Dorfman
    • , Kurt D’Andrea
    • , Brandon M. Wenz
    • , Shujing Liu
    • , Lakshmi Chilukuri
    • , Andrew Kozlov
    • , Mary Carberry
    • , Lydia Giles
    • , Melanie W. Kier
    • , Felix Quagliarello
    • , Suzanne McGettigan
    • , Kristin Kreider
    • , Lakshmanan Annamalai
    • , Qing Zhao
    • , Robin Mogg
    • , Wei Xu
    • , Wendy M. Blumenschein
    • , Jennifer H. Yearley
    • , Gerald P. Linette
    • , Ravi K. Amaravadi
    • , Lynn M. Schuchter
    • , Ramin S. Herati
    • , Bertram Bengsch
    • , Katherine L. Nathanson
    • , Michael D. Farwell
    • , Giorgos C. Karakousis
    • , E. John Wherry
    •  & Tara C. Mitchell
  • Letter |

    Clinical insights from patients with a rare genetic skeletal disorder led to the discovery of the first case of a pathogenic gain-of-function miRNA mutation.

    • Giedre Grigelioniene
    • , Hiroshi I. Suzuki
    • , Fulya Taylan
    • , Fatemeh Mirzamohammadi
    • , Zvi U. Borochowitz
    • , Ugur M. Ayturk
    • , Shay Tzur
    • , Eva Horemuzova
    • , Anna Lindstrand
    • , Mary Ann Weis
    • , Gintautas Grigelionis
    • , Anna Hammarsjö
    • , Elin Marsk
    • , Ann Nordgren
    • , Magnus Nordenskjöld
    • , David R. Eyre
    • , Matthew L. Warman
    • , Gen Nishimura
    • , Phillip A. Sharp
    •  & Tatsuya Kobayashi
  • Publisher Correction |

    • Jinglan Zhang
    • , Jianli Li
    • , Jennifer B. Saucier
    • , Yanming Feng
    • , Yanjun Jiang
    • , Jefferson Sinson
    • , Anne K. McCombs
    • , Eric S. Schmitt
    • , Sandra Peacock
    • , Stella Chen
    • , Hongzheng Dai
    • , Xiaoyan Ge
    • , Guoli Wang
    • , Chad A. Shaw
    • , Hui Mei
    • , Amy Breman
    • , Fan Xia
    • , Yaping Yang
    • , Anne Purgason
    • , Alan Pourpak
    • , Zhao Chen
    • , Xia Wang
    • , Yue Wang
    • , Shashikant Kulkarni
    • , Kwong Wai Choy
    • , Ronald J. Wapner
    • , Ignatia B. Van den Veyver
    • , Arthur Beaudet
    • , Sheetal Parmar
    • , Lee-Jun Wong
    •  & Christine M. Eng