Nature Medicine Contents: February 2017 Volume 23 Number 2 pp 137-264

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Drug discovery research grants - awards up to $700,000
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February 2017 Volume 23, Issue 2

News and Views

Nature Reviews Clinical Oncology: Poster on Liquid biopsies in the clinic

This poster highlights the emerging developments in the detection and analysis of circulating tumour material, and its use as liquid biopsies at different stages of tumour evolution.

Available to download free online

Produced with support from
Menarini Silicon Biosystems, Inc

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The Biology of Regenerative Medicine (25-27 April 2017) 
This conference aims to understand the biology that underpins the success or failure of regenerative processes. We will explore the relationship between stem cell biology and regenerative biology so that both can be fully exploited to treat disease.
Deadlines: Bursary: 28 Feb / Abstracts: 14 Mar / Registration: 28 Mar 
Nature Outlook: Precision Medicine

Health care that is tailored on the basis of an individual's genes, lifestyle or environment, is not a modern concept. But advances in genetics and the growing availability of health data for researchers and physicians promise to make this new era of medicine more personalized than ever before.

Access the Outlook free online

Sponsored by:
Illumina, Inc.



The double edge of cancer immunotherapy   p137
Immune-related adverse effects are understudied and not easily treatable risks of cancer immunotherapy. Concerted research efforts to understand the mechanisms of immunotherapy-triggered responses are crucial for developing better treatments.



Channeling chip power: Tissue chips are being put to the test by industry   pp138 - 140
Cassandra Willyard

Correction   p140

Boardroom bound: Efforts to bring more women into biomed industry's top ranks   pp141 - 143
Shraddha Chakradhar

Mapping the mind: A new tool reveals uncharted territories in the brain   pp144 - 146
Madeleine Johnson

News and Views


Exhausting alloreactivity of donor-derived CAR T cells   pp147 - 148
Maksim Mamonkin and Helen E Heslop
A study in mouse models of allogeneic stem cell transplantation with donor-derived CD19 chimeric antigen receptor (CAR) T cells for the treatment of relapsed B cell malignancies indicates that T cell exhaustion might have a role in preventing allogeneic reactivity of CD19 CAR T cells.

See also: Letter by Ghosh et al.

HDAC3 sets the timer on muscle fuel switching   pp148 - 150
Deborah M Muoio
In a recent study in mice, it is shown that circadian oscillations in genomic histone deactylase 3 (HDAC3) occupancy influence fuel switching and carbon flux in muscle to regulate glucose homeostasis and exercise performance.

See also: Article by Hong et al.

Nature Medicine
JOBS of the week
Doctoral Students in Molecular Medicine
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Doctoral Students in Molecular Medicine
Danish Research Institute for Translational Neuroscience (DANDRITE) / Nordic EMBL Partnership
Radiation Oncology Research Faculty, NYU Langone School of Medicine
NYU Langone Medical Center
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α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies   pp1 - 13
Yvette C Wong and Dimitri Krainc
Two decades ago, α-synuclein was identified as a key player in Parkinson's disease pathogenesis. Wong and Krainc review the upstream factors and downstream cellular mechanisms associated with α-synuclein toxicity and discuss therapeutic efforts to target synucleinopathies.

Unexplored opportunities in the druggable human genome

This poster presents a categorization of human proteins based on the amount of data on them, highlighting a knowledge deficit and indicating novel drug discovery opportunities. 

Download the Poster free online

Produced with support from:

Illuminating the Druggable Genome Knowledge Management Center 



Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia   pp164 - 173
Gregory Corder, Vivianne L Tawfik, Dong Wang, Elizabeth I Sypek, Sarah A Low et al.
μ opioid receptors (MORs) expressed on primary afferent nociceptor neurons are responsible for two maladaptive side-effects of chronic opioid use: opioid tolerance and opioid-induced hyperalgesia (pain). A combination therapy of opioid receptor agonism plus peripheral-restricted MOR antagonism abrogates these side-effects while preserving opioid analgesia in rodent models of peri-operative and chronic pain.

Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states   pp174 - 184
David Furman, Junlei Chang, Lydia Lartigue, Christopher R Bolen, Francois Haddad et al.
Differential expression of inflammasome gene modules and inflammasome-activating metabolites correlates with interleukin-1β expression, hypertension, arterial stiffness and longevity in older individuals.

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals   pp185 - 191
Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis et al.
Florian Klein and colleagues report that treating viremic HIV-1-infected individuals with the broadly neutralizing antibody 10-1074 reduced virus levels in blood, but antibody-resistant virus did emerge.

A chikungunya fever vaccine utilizing an insect-specific virus platform   pp192 - 199
Jesse H Erasmus, Albert J Auguste, Jason T Kaelber, Huanle Luo, Shannan L Rossi et al.
New vaccine approaches that safely elicit immunity are needed to protect against infectious disease. Erasmus et al. report their development of an insect-virus-based platform that they use to engineer a protective vaccine against chikungunya fever.

Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome   pp200 - 212
Jorge Oller, Nerea Mendez-Barbero, E Josue Ruiz, Silvia Villahoz, Marjolijn Renard et al.
Loss of the metalloproteinase Adamts1 leads to aortic pathology in mice due to increased NOS2-dependent NO production. Decreased Adamts1 expression, associated with increased NOS2 expression, occurs in Marfan syndrome (MFS) mice and in MFS patients, and NOS2 inhibition prevents and reverses aortic pathology in MFS mice.

Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader-Willi syndrome   pp213 - 222
Yuna Kim, Hyeong-Min Lee, Yan Xiong, Noah Sciaky, Samuel W Hulbert et al.
A pharmacological screen has identified the histone methyltransferase G9a as a target to reactivate imprinted genes in a mouse model of Prader-Willi Syndrome that improves growth and survival.

Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion   pp223 - 234
Sungguan Hong, Wenjun Zhou, Bin Fang, Wenyun Lu, Emanuele Loro et al.
Genetic deletion of HDAC3, a circadian epigenome regulator, specifically in skeletal muscle alters amino acid metabolism, leading to increased muscle endurance but at the cost of whole-body insulin resistance.

See also: News and Views by Muoio

Nature Biomedical Engineering - NOW LIVE

The first issue of Nature Biomedical Engineering is now live and available for free. 
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Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors   pp235 - 241
Shawn M Davidson, Oliver Jonas, Mark A Keibler, Han Wei Hou, Alba Luengo et al.
Using a device implanted in KRAS-driven pancreatic tumors, authors demonstrate that cancer cells incorporate proteins in their microenvironment as a source of amino acids. This work provides a novel approach to study tumor metabolism that could be applied with therapeutic purposes.

Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity   pp242 - 249
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi et al.
Allogeneic chimeric antigen receptor (CAR) T cells are capable of inducing graft-versus-host disease (GVHD) in recipients, yet this is not commonly seen in the clinic. Marcel van den Brink, Michel Sadelain and colleagues show that alloreactive CAR T cells have reduced effector function due to signaling through the CAR and T cell receptor, resulting in reduced GVHD, while the graft-versus-leukemia effect is maintained by non-alloreactive CAR T cells.

See also: News and Views by Mamonkin & Heslop

SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia   pp250 - 255
Constanze Schneider, Thomas Oellerich, Hanna-Mari Baldauf, Sarah-Marie Schwarz, Dominique Thomas et al.
The therapeutic response of acute myeloid leukemia to the nucleoside analog Ara-C is controlled by SAMHD1, an enzyme that hydrolyzes the active metabolite Ara-CTP.

Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies   pp256 - 263
Nikolas Herold, Sean G Rudd, Linda Ljungblad, Kumar Sanjiv, Ida Hed Myrberg et al.
The therapeutic response of acute myelogenous leukemia to the nucleoside analog ara-C is controlled by SAMHD1, an enzyme that hydrolyzes the activemetabolite ara-CTP.



Corrigendum: Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes   p264
Jenny Aurielle B Babon, Megan E DeNicola, David M Blodgett, Inne Crevecoeur, Thomas S Buttrick et al.

Corrigendum: Zika viral dynamics and shedding in rhesus and cynomolgus macaques   p264
Christa E Osuna, So-Yon Lim, Claire Deleage, Bryan D Griffin, Derek Stein et al.

Corrigendum: Human antibody repertoire after VSV-Ebola vaccination identifies novel targets and virus-neutralizing IgM antibodies   p264
Surender Khurana, Sandra Fuentes, Elizabeth M Coyle, Supriya Ravichandran, Richard T Davey Jr et al.



Erratum: Resting-state connectivity biomarkers define neurophysiological subtypes of depression   p264
Andrew T Drysdale, Logan Grosenick, Jonathan Downar, Katharine Dunlop, Farrokh Mansouri et al.

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