Nov 01, 2021

Advisory Board and Contents

TrendsTalk

Stories in Molecular Medicine November 2021
Life experiences influence our research and motivate us to ask scientific questions and shape research goals. Here, Trends in Molecular Medicine authors share their journey in science. Their portraits highlight the diversity of scientists and that there is no standard career in science. We hope that these inspiring stories help to build bridges of understanding between science and society and motivate others to join the melting pot of scientific disciplines united in Trends in Molecular Medicine.

Spotlight

Special delivery! CAR-T cells transport RN7SL1 to the tumor microenvironment
• W. Sam Nutt,
• Shivani Srivastava
In a recent Cell publication, Johnson et al. demonstrate that engineering chimeric antigen receptor (CAR)-T cells to produce RN7SL1, a novel RNA adjuvant that activates the viral sensors RIG-I and MDA5, improves intrinsic CAR-T cell function, activates tumor-infiltrating myeloid cells, and enhances endogenous tumor-specific T cell responses, resulting in improved tumor control despite CAR antigen loss in multiple mouse models.

Opinion

Targeting synaptic plasticity in schizophrenia: insights from genomic studies
• Arne W. Mould,
• Nicola A. Hall,
• Ira Milosevic,
• Elizabeth M. Tunbridge
Patients with schizophrenia experience cognitive dysfunction and negative symptoms that do not respond to current drug treatments. Historical evidence is consistent with the hypothesis that these deficits are due, at least in part, to altered cortical synaptic plasticity (the ability of synapses to strengthen or weaken their activity), making this an attractive pathway for therapeutic intervention. However, while synaptic transmission and plasticity is well understood in model systems, it has been challenging to identify specific therapeutic targets for schizophrenia.

Reviews

Skeletal muscle mitochondrial network dynamics in metabolic disorders and aging
• Ciarán E. Fealy,
• Lotte Grevendonk,
• Joris Hoeks,
• Matthijs K.C. Hesselink
With global demographics trending towards an aging population, the numbers of individuals with an age-associated loss of independence is increasing. A key contributing factor is loss of skeletal muscle mitochondrial, metabolic, and contractile function. Recent advances in imaging technologies have demonstrated the importance of mitochondrial morphology and dynamics in the pathogenesis of disease. In this review, we examine the evidence for altered mitochondrial dynamics as a mechanism in age and obesity-associated loss of skeletal muscle function, with a particular focus on the available human data.

A map of the altered glioma metabolism
• Ruhi Deshmukh,
• Maria Francesca Allega,
• Saverio Tardito
The frequent occurrence of neomorphic isocitrate dehydrogenase 1 (IDH1) mutations in low-grade glioma led to an IDH-centric classification of these tumors. However, exploiting metabolic alterations of glioma for diagnostic imaging and treatment has marginally improved patients’ prognosis. Here we discuss the nutritional microenvironment of glioma, shaped by the distinctive dependence of the brain on glucose and ketone bodies for energy, and on amino acids for neurotransmission. We highlight the progress in metabolic applications for glioma diagnosis and therapy, and present a map that streamlines the rewired glioma metabolism.

Enhancers in disease: molecular basis and emerging treatment strategies
• Annique Claringbould,
• Judith B. Zaugg
Open Access
Enhancers are genomic sequences that play a key role in regulating tissue-specific gene expression levels. An increasing number of diseases are linked to impaired enhancer function through chromosomal rearrangement, genetic variation within enhancers, or epigenetic modulation. Here, we review how these enhancer disruptions have recently been implicated in congenital disorders, cancers, and common complex diseases and address the implications for diagnosis and treatment. Although further fundamental research into enhancer function, target genes, and context is required, enhancer-targeting drugs and gene editing approaches show great therapeutic promise for a range of diseases.
Secondary failure: immune responses to approved protein therapeutics
• H.A. Daniel Lagassé,
• Quinn McCormick,
• Zuben E. Sauna
Recombinant therapeutic proteins are a broad class of biological products used to replace dysfunctional human proteins in individuals with genetic defects (e.g., factor VIII for hemophilia) or, in the case of monoclonal antibodies, bind to disease targets involved in cancers, autoimmune disorders, or other conditions. Unfortunately, immunogenicity (immune response to the drug) remains a key impediment, potentially affecting the safety and efficacy of these therapeutics. Immunogenicity risk is routinely evaluated during the licensure of therapeutic proteins.

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