Volume 21 Issue 12, December 2015

Our list of newsmakers this year includes some standout personalities, from a price-hiking, former hedge fund manager to a persistent and now-well-recognized immunotherapy advocate.

In the past year, we have witnessed a flurry of debates in the biomedical arena, from the uproar surrounding price gouging to the ethical hand-wringing over the use of CRISPR-Cas9 technology for genome editing. Beyond these topics, 2015 also made news with vaccine mandates, epigenetic mapping and even an accidental shipment of anthrax.

This year's newsworthy drugs made strides against cancer, heart disease and more. Some drugs made headlines for their inability to succeed in clinical trials, and others are still waiting, stuck in limbo, for a chance to move forward in the pipeline. Here is a look at a few of them.

This year saw a whirlwind of insights gleaned into topics ranging from heart cell proliferation to organoid modeling. Here are a few of the research papers detailing some of these intriguing discoveries.

Microbiota depletion promotes type 2 cytokine signaling and browning in white adipose tissue of mice.

Duchenne muscular dystrophy (DMD) is a devastating X-linked disease that is characterized by progressive muscle degeneration and caused by mutations in dystrophin. Dystrophin is critical for myofiber structural integrity, but a new study reveals an additional important role for this protein in muscle stem cells.

A new study provides a rationale for the use of poly (ADP-ribose) polymerase (PARP) inhibitors to trigger irreparable DNA damage as a therapeutic approach in acute myeloid leukemia (AML). It also provides support for combining PARP inhibitors with agents that reduce HOXA9 protein levels.

Six leaders in aging research discuss how to translate their findings in the field.

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

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.

Toren Finkel reviews how metabolism and aging are connected, and highlights pathways that could be pharmacologically targeted to combat aging and age-related disease.

In this Review, Jan van Deursen and his colleagues discuss the recent progress in understanding the origin and identity of senescent cells in ageing and their contribution to age-related disease, in addition to discussing the potential for targeting these cells to counteract disease.

Treatment with the common diuretic bumetanide during a susceptible developmental window prevents epileptogenesis in a mouse model of a genetic epileptic encephalopathy.

In human FMCD tissue, a small fraction of pS6⁺ neurons are enriched for somatic activating mutations of the PI3K-AKT-mTOR pathway. Sparse electroporation of the AKT3 mutation into the developing mouse brain causes a reelin-dependent, non–cell autonomous disruption of neuronal migration, leading to impaired cortical lamination and seizure-like epileptiform EEG activity.

Dystrophin is expressed in muscle stem cells, in which it regulates their cell division and proper repopulation.

Michael Diamond and colleagues report that TAM receptor deficiency exacerbated West Nile Virus infection in mice and increased the permeability of the blood-brain barrier.

An inhibitor of Aurora kinase promotes megakaryocytic differentiation of cells from patients with primary myelofibrosis and shows antifibrotic effects in mouse models of this disease.

The authors uncover a therapeutic vulnerability to PARP inhibition of acute myeloid leukemias driven by certain oncogenic fusions, and they unravel the mechanisms by which these cancers rely on DNA damage and repair pathways for growth.

The authors identify EZH2 as a general underlying dependency of tumors with mutations in the SWI/SNF chromatin regulator complex, and they show that EZH2's pro-tumorigenic role may be dependent on non-catalytic activities. This may pose new opportunities and challenges for using EZH2 as a cancer therapy target.

Browning of white adipose tissue is induced by depletion of the microbiota, improving metabolic disease and reducing obesity.

Kenzo Tokunaga and colleagues report that MARCH8 inhibits the incorporation of the HIV-1 envelope glycoprotein into virus particles, thereby reducing viral infectivity.

Ralph Baric, Vineet Menachery and colleagues characterize a SARS-like coronavirus circulating in Chinese horseshoe bats to determine its potential to infect primary human airway epithelial cells, cause disease in mice and respond to available therapeutics.

Understanding tumor metastasis is crucial to developing more effective cancer therapies. Here McCreery et al. analyzed the mutational profile of metastases from chemically induced skin tumors in mice and found that parallel evolution of synchronously disseminated tumor cells underlies most metastasis.

Aging is associated with functional impairments in cellular pathways controlling genomic stability, proteostasis and metabolism, and is a major risk factor for several of the most prevalent diseases. This series of Reviews and Perspectives highlights the recent data that point toward the specific molecular pathways that are perturbed during aging and discuss potential ways to manipulate these pathways to prevent or alleviate age-related diseases.