Perspectives

  • Perspective |

    The clinical translation of stem-cell-based therapeutic interventions has its own ethical and policy challenges requiring collaboration among wide-ranging stakeholders.

    • Amanda MacPherson
    •  & Jonathan Kimmelman
  • Perspective |

    The TRANSNEURO Consortium shares valuable insights that may facilitate planning of human pluripotent stem-cell-derived dopamine cell transplants for future clinical trials on Parkinson’s disease.

    • Roger A. Barker
    • , Krista Farrell
    • , Natalie Valle Guzman
    • , Xiaoling He
    • , Stanley E. Lazic
    • , Sarah Moore
    • , Robert Morris
    • , Pamela Tyers
    • , Ruwani Wijeyekoon
    • , Danielle Daft
    • , Sam Hewitt
    • , Viswas Dayal
    • , Thomas Foltynie
    • , Zinovia Kefalopoulou
    • , Philipp Mahlknecht
    • , Nick P. Lao-Kaim
    • , Paola Piccini
    • , Hjalmar Bjartmarz
    • , Anders Björklund
    • , Olle Lindvall
    • , Jenny Nelander-Wahlestedt
    • , Malin Parmar
    • , Gesine Paul
    • , Hakan Widner
    • , Alistair Church
    • , Stephen Dunnett
    • , Kathryn Peall
    • , Anne Rosser
    • , Jean Marc Gurruchaga
    • , Stéphane Palfi
    • , Tobias Piroth
    •  & Christian Winkler
  • 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
  • Perspective |

    The emerging field of precision epidemiology allows the personalized diagnosis, tracking and treatment of infectious diseases.

    • Jason T. Ladner
    • , Nathan D. Grubaugh
    • , Oliver G. Pybus
    •  & Kristian G. Andersen
  • Perspective |

    A primer for deep-learning techniques for healthcare, centering on deep learning in computer vision, natural language processing, reinforcement learning, and generalized methods.

    • Andre Esteva
    • , Alexandre Robicquet
    • , Bharath Ramsundar
    • , Volodymyr Kuleshov
    • , Mark DePristo
    • , Katherine Chou
    • , Claire Cui
    • , Greg Corrado
    • , Sebastian Thrun
    •  & Jeff Dean
  • Perspective |

    A neoadjuvant approach using combined anti-CTLA4/anti-PD1 treatment prior to lymph node surgery is evaluated in two phase I trials of later stage melanoma finding this a therapeutic angle worth pursuing.

    • Caroline Robert
  • Perspective |

    In this Perspective, Michael Czech presents evidence for whether hyperinsulinemia occurs before insulin resistance upon overfeeding or high-fat diet feeding, or whether insulin resistance causes hyperinsulinemia, thus attempting to delineate the relationship between hyperinsulinemia, obesity and insulin resistance.

    • Michael P Czech
  • Perspective |

    In this Perspective, June, Bluestone and Warshauer discuss potential cellular and molecular explanations for the autoimmunity often associated with immunotherapy, and propose additional research and changes to reporting practices to aid efforts to understand and minimize these toxic side effects.

    • Carl H June
    • , Jeremy T Warshauer
    •  & Jeffrey A Bluestone
  • Perspective |

    Abi-Dargham and Horga discuss the challenges of developing and standardizing brain-imaging technologies to aid with the diagnosis and treatment of psychiatric disorders.

    • Anissa Abi-Dargham
    •  & Guillermo Horga
  • Perspective |

    Recent studies have led to the identification of genetic loci that are shared between psychiatric disorders. Here O’Donovan and Owen argue that it is unlikely that risk alleles exist that are singular to any one such disorder.

    • Michael C O'Donovan
    •  & Michael J Owen
  • Perspective |

    The International AIDS Society Towards a Cure Working Group lays out its scientific strategy to achieve a cure for HIV.

    • Steven G Deeks
    • , Sharon R Lewin
    • , Anna Laura Ross
    • , Jintanat Ananworanich
    • , Monsef Benkirane
    • , Paula Cannon
    • , Nicolas Chomont
    • , Daniel Douek
    • , Jeffrey D Lifson
    • , Ying-Ru Lo
    • , Daniel Kuritzkes
    • , David Margolis
    • , John Mellors
    • , Deborah Persaud
    • , Joseph D Tucker
    • , Françoise Barre-Sinoussi
    • , International AIDS Society Towards a Cure Working Group
    • , Galit Alter
    • , Judith Auerbach
    • , Brigitte Autran
    • , Dan H Barouch
    • , Georg Behrens
    • , Marina Cavazzana
    • , Zhiwei Chen
    • , Éric A Cohen
    • , Giulio Maria Corbelli
    • , Serge Eholié
    • , Nir Eyal
    • , Sarah Fidler
    • , Laurindo Garcia
    • , Cynthia Grossman
    • , Gail Henderson
    • , Timothy J Henrich
    • , Richard Jefferys
    • , Hans-Peter Kiem
    • , Joseph McCune
    • , Keymanthri Moodley
    • , Peter A Newman
    • , Monique Nijhuis
    • , Moses Supercharger Nsubuga
    • , Melanie Ott
    • , Sarah Palmer
    • , Douglas Richman
    • , Asier Saez-Cirion
    • , Matthew Sharp
    • , Janet Siliciano
    • , Guido Silvestri
    • , Jerome Singh
    • , Bruno Spire
    • , Jeffrey Taylor
    • , Martin Tolstrup
    • , Susana Valente
    • , Jan van Lunzen
    • , Rochelle Walensky
    • , Ira Wilson
    •  & Jerome Zack
  • Perspective |

    • Lillian L Siu
    • , Mark Lawler
    • , David Haussler
    • , Bartha Maria Knoppers
    • , Jeremy Lewin
    • , Daniel J Vis
    • , Rachel G Liao
    • , Fabrice Andre
    • , Ian Banks
    • , J Carl Barrett
    • , Carlos Caldas
    • , Anamaria Aranha Camargo
    • , Rebecca C Fitzgerald
    • , Mao Mao
    • , John E Mattison
    • , William Pao
    • , William R Sellers
    • , Patrick Sullivan
    • , Bin Tean Teh
    • , Robyn L Ward
    • , Jean Claude ZenKlusen
    • , Charles L Sawyers
    •  & Emile E Voest
  • Perspective |

    In this Perspective, the mechanisms by which proteostasis is coordinated within and between cells is discussed with an emphasis on how these mechanisms are deregulated upon aging.

    • Susmita Kaushik
    •  & Ana Maria Cuervo
  • Perspective |

    In this Perspective, the current approaches to drug aging, and how new approaches may be developed in the future are discussed.

    • Celine E Riera
    •  & Andrew Dillin
  • Perspective |

    In this Perspective, the authors discuss the currently available models for psychiatric disease modeling. They present a framework for translating new knowledge by placing more emphasis on identifying neurophysiological defects.

    • Tobias Kaiser
    •  & Guoping Feng
  • Perspective |

    In this Perspective, the authors discuss the importance of intrinsic and extrinsic factors in muscle regeneration, and they conclude that both are necessary for the action of muscle stem cells in the aging process.

    • Helen M Blau
    • , Benjamin D Cosgrove
    •  & Andrew T V Ho
  • Perspective |

    In this Perspective, attendees of the Herrenhausen Tumour Heterogeneity meeting discuss the challenges in understanding tumour heterogeneity and propose ways forward for overcoming these hurdles.

    • Ash A Alizadeh
    • , Victoria Aranda
    • , Alberto Bardelli
    • , Cedric Blanpain
    • , Christoph Bock
    • , Christine Borowski
    • , Carlos Caldas
    • , Andrea Califano
    • , Michael Doherty
    • , Markus Elsner
    • , Manel Esteller
    • , Rebecca Fitzgerald
    • , Jan O Korbel
    • , Peter Lichter
    • , Christopher E Mason
    • , Nicholas Navin
    • , Dana Pe'er
    • , Kornelia Polyak
    • , Charles W M Roberts
    • , Lillian Siu
    • , Alexandra Snyder
    • , Hannah Stower
    • , Charles Swanton
    • , Roel G W Verhaak
    • , Jean C Zenklusen
    • , Johannes Zuber
    •  & Jessica Zucman-Rossi
  • Perspective |

    In this Perspective, Fred De Sauvage and Stephen Gould discuss the suitability of different mouse models for modeling cancer pathogenic processes, with an emphasis on applicability to developing cancer therapies.

    • Stephen E Gould
    • , Melissa R Junttila
    •  & Frederic J de Sauvage
  • Perspective |

    Understanding the regenerative capacity of the adult mammalian heart and the cell types involved is essential for developing therapies for cardiac repair.

    • Jop H van Berlo
    •  & Jeffery D Molkentin
  • Perspective |

    Our understanding of stem cell biology is increasing, but the translation of this knowledge into regenerative medicine therapies for aged or diseased tissues is proving challenging. In this Perspective, four experts in the field discuss strategies for overcoming the major hurdles facing the translational regenerative field.

    • Stefanie Dimmeler
    • , Sheng Ding
    • , Thomas A Rando
    •  & Alan Trounson
  • Perspective |

    Synthetic lethality describes a situation in which defects in either one of two genes are not detrimental, but combining defects in the two genes is lethal. The targeting of BRCA-deficient tumors by PARP inhibitors is the first clinical example utilizing the principle of synthetic lethality to treat cancer. Despite the promise of this approach, a number of resistance mechanisms have been identified, and this Perspective describes these mechanisms and their clinical relevance.

    • Christopher J Lord
    •  & Alan Ashworth
  • Perspective |

    There is much interest in the applications of pluripotent stem cells for regenerative medicine. In this Perspective, the authors discuss the factors that might contribute to the potential risk of tumorigenicity from pluripotent stem cell therapies. They also outline recent developments in techniques that allow the sorting of tumorigenic species from nontumorigenic cells and offer a viewpoint into the future hurdles for moving pluripotent stem cell–based therapies from bench to bedside.

    • Andrew S Lee
    • , Chad Tang
    • , Mahendra S Rao
    • , Irving L Weissman
    •  & Joseph C Wu
  • Perspective |

    Persistence of hepatitis C virus contributes to chronic infection, which can lead to liver fibrosis and even liver cancer. Different factors, such as host genetics and immunity and viral immune evasion strategies, account for the outcome of the infection and the patient response to antivirals. This Perspective discusses how the interaction of these factors modulates viral immunity and how they might be used to identify the key targets to mount an effective immune response that will clear the virus and improve drug response.

    • Stacy M Horner
    •  & Michael Gale Jr
  • Perspective |

    Autism spectrum disorders (ASDs) are a clinically heterogeneous group of neurodevelopmental disorders characterized by social and communication deficits and repetitive behaviors. In a subset of individuals with ASD, mutations in genes involved in synaptic function have been identified, and this Perspective discusses the evidence from mouse models of ASD that synaptic deficits can be ameliorated in the mature brain. The authors also suggest a strategy for designing more informative clinical trials for ASD therapies that stratify patients according to their specific synaptic mutations.

    • Richard Delorme
    • , Elodie Ey
    • , Roberto Toro
    • , Marion Leboyer
    • , Christopher Gillberg
    •  & Thomas Bourgeron
  • Perspective |

    Rapid and effective host responses keep herpes simplex virus-2 (HSV-2) at bay, preventing genital mucosa lesions. However, periodic shedding and frequent reactivation of the latent virus allow for silent transmission, posing a challenge to virus elimination. The rapid clearance of HSV-2 in the genital mucosa by resident and virus-specific immune cells that persist in the mucosa suggests new ways to harness the immune system to develop effective therapies.

    • Joshua T Schiffer
    •  & Lawrence Corey
  • Perspective |

    Malaria's death toll has been reduced as a result of global efforts over the last decade. Yet the rise of drug resistance and the plateauing of funding are still obstacles to eradicating the disease and reducing malaria burden. This review brings up the goals and challenges faced by researchers and the public health workforce and a way forward to effectively control and eliminate malaria.

    • Pedro L Alonso
    •  & Marcel Tanner
  • Perspective |

    There is renewed enthusiasm in developing an HIV vaccine and in understanding the requirements to elicit broadly neutralizing HIV-specific antibodies. In May 2012, a workshop convened researchers to discuss the interplay of CD4+ T cell and antibody responses to help identify key questions and areas of research that can inform future vaccine development. This Perspective summarizes the discussion of three main topics on the role of CD4+ T cells in HIV vaccine design.

    • Hendrik Streeck
    • , M Patricia D'Souza
    • , Dan R Littman
    •  & Shane Crotty
  • Perspective |

    The term 'mesenchymal stem cells' is widely used, yet the capabilities and characteristics of these postnatal bone marrow stem cells still warrant further examination. A further understanding and clarification of the true potential of these mesenchymal stem cells is crucial for their appropriate exploitation in the clinic.

    • Paolo Bianco
    • , Xu Cao
    • , Paul S Frenette
    • , Jeremy J Mao
    • , Pamela G Robey
    • , Paul J Simmons
    •  & Cun-Yu Wang
  • Perspective |

    Large-scale sequencing has recently revealed the presence of highly complex, localized chromosomal rearrangements in cancer genomes. The authors discuss the evidence that such rearrangements can occur through at least two mechanisms: chromosomal shattering (chromothripsis) and template switching initiated by local defective DNA replication (chromoanasynthesis). They propose use of the term chromoanagenesis to describe this class of rearrangements, regardless of the initiating mechanism.

    • Andrew J Holland
    •  & Don W Cleveland