Volume 25 Issue 5, May 2019

Volume 25 Issue 5

Modeling injury in the developing human brain

Premature infants often undergo repeated episodes of hypoxia and can develop a condition called encephalopathy of prematurity with long-term neurodevelopmental impairments. In this issue, Paşca et al. use human pluripotent stem cells to develop a three-dimensional brain-organoid-based model of early brain injury and investigate the cellular effects of oxygen deprivation on human cortical development. The cover illustrates efforts to generate in vitro cellular models of the developing human brain to study and prevent injury.

Image credit: Andy Pots. Cover design: Erin Dewalt

Editorial

  • Editorial |

    Immune interventions capable of preventing or eradicating HIV infection have yet to achieve broad success in humans. Renewed vigor in the clinical trial arena may bring us closer to that goal.

News Feature

  • News Feature |

    • Hannah Valantine
    • , Elizabeth Travis
    • , Wafa El-Adhami
    • , Isabelle Vernos
    • , Laura Mosqueda
    • , Elizabeth Wayne
    • , Fiona Kearns-Zimmerman
    • , Lauren Bonefont
    • , Sandhya S. Visweswariah
    • , Wuraola Akande-Sholabi
    •  & Jessica Polka

Turning Points

  • Turning Points |

    Ami Bhatt is a physician-scientist and assistant professor of medicine and genetics at Stanford University. Her research deploys next-generation sequencing to explore host–microbiome interactions, including those in cancer.

    • Ami S. Bhatt
  • Turning Points |

    Max Nieuwdorp is an internist, endocrinologist and vascular medicine specialist at Amsterdam University Medical Centers. He chairs the Diabetes Center there and is chief of the Department and Laboratory of Vascular Medicine.

    • Max Nieuwdorp

Research Highlights

News & Views

  • News & Views |

    Three innovative precision medicine studies show the utility of evidence beyond that from tumor DNA sequencing to guide therapy in patients with cancer.

    • Christophe Le Tourneau
    • , Edith Borcoman
    •  & Maud Kamal
  • News & Views |

    Human survivors of Ebola virus disease are more likely than uninfected controls to develop memory loss, uveitis, and other abnormal conditions, and Ebola virus remains in semen much longer than previously thought.

    • Daniel S. Chertow

Perspectives

  • 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

Brief Communications

Letters

  • 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 |

    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
  • 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
  • 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
  • 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 |

    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

Articles

  • 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
  • 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
  • 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 |

    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

Resources

  • 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
  • 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

Amendments & Corrections