Glioblastomas are high-grade and aggressive CNS tumors. Due to heterogeneous composition, rapid growth, and suppressive immune microenvironment, gliomablastomas remain difficult to successfully treat. JCI editors Amy Heimberger, Daniel Brat, and Maciej Lesniak curated the reviews in this issue’s series to confront the many aspects of immune involvement in these clinically challenging tumors. Reviews in this series describe how tumor-associated macrophages, microglia, and neutrophils modulate glioblastoma progression and therapy response. They also explore new concepts for targeting the immune microenvironment in glioblastoma, including strategies targeting immunometabolism or epigenetic regulation, personalized immunotherapy approaches, and next-generation antigen presenting cell-based therapies.
Published February 2023
The Stanley J. Korsmeyer Award recognizes the outstanding achievements of ASCI members in advancing knowledge in a specific field and in mentoring future generations of life science researchers. The recognition, which was first known as the ASCI Award, was renamed in 2006 in honor of Dr. Stanley J. Korsmeyer, a dedicated and accomplished physician-scientist and mentor who was the first recipient in 1998 and who passed away in 2005. 2023 marks the 25th Anniversary of the Korsmeyer Award, and the ASCI and JCI commemorate this milestone with a collection of articles contributed by the award's past winners. Articles will be added to this collection throughout the year.
Published January 2023
Aging plays a central role in many chronic diseases affecting all systems of the body. Nine hallmarks of aging have been identified: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. This new review series on Aging closely examines how these hallmarks contribute to the initiation and progression of disease. Curated by series editor Dr. James Kirkland, topics span aging’s role in immune system function, cancer, cognitive decline and neurodegenerative disease, and metabolism. The reviews also discuss the latest developments in senotherapeutic strategies that destroy senescent cells, reverse senescence, or target specific aging hallmarks with a critical eye.
Published July 2022
Next-generation sequencing (NGS) technology enables rapid, high-throughput sequencing of thousands of genes or even entire genomes. The speed and scale of these techniques makes them powerful tools in medicine, creating an opportunity to build and search deep genetic databases, refine diagnoses, and inform precision medicine approaches. In this series, designed by Ben H. Park, five reviews describe how NGS is revolutionizing clinical insights into disease. Wensel et al. compare key NGS methods for investigating the microbiome, emphasizing the need for careful study design and validation as these techniques become more widely adopted. Schuler et al. outline the capabilities and limitations of current genetic testing approaches and provide examples of clinical scenarios in which NGS was combined with other strategies to make a diagnosis. The contribution from Waarts et al. describes how NGS has contributed to the identification of targetable mutations in a range of cancers and discusses challenges to achieving maximal therapeutic benefit of targeted treatments. Halima et al. focus on high-throughput NGS approaches that are revealing the fundamental genetic processes that govern immunity, influencing how we design and implement cancer immunotherapy. Finally, Dang and Park’s review on circulating tumor DNA discusses the advantages of blood-based diagnosis as well as strategies to overcome technical limitations and improve detection of cancer in its earliest stages.
Published June 2022
Cardiovascular diseases remain a leading cause of death worldwide, and treatment is complicated by the inadequacies of available therapies. This collection of reviews, developed by Daniel P. Kelly, explores emerging strategies for treating a range of cardiac pathologies, including: recent discoveries of epigenetic regulators that can be targeted to combat cardiac fibrosis, state of the art in genome-editing therapies, interactions of the vascular endothelium with metabolic tissues, current understanding of myosin modulators, and novel targets for treating dyslipidemia. Together, the reviews provide a broad update on numerous advances in cardiovascular medicine.
Published March 2022
Studies of the metabolic reprogramming that occurs in activated immune cells may reveal critical therapeutic nodes in immune-related disorders and provide guidance for fine-tuning immune-targeted therapies. In this series, curated by Jonathan Powell, reviews focus on the metabolic pathways underlying immune involvement in disease and treatment: strategies to enhance immune memory, vaccine responses, and cancer immunotherapy by optimizing memory T cell metabolism; metabolites that modulate immune function; the metabolites of the tumor microenvironment that reshape immune cell function in the tumor’s favor; metabolism-targeted small molecule inhibitors developed for oncology applications; and dyslipidemia in autoimmune rheumatic diseases. Together, the reviews illustrate the complex energetic dynamics supporting function and dysfunction in the innate and adaptive immune systems.
Published January 2022
Animals, plants, and bacteria all display behavioral patterns that coincide with Earth’s light and dark cycles. These oscillating behaviors are the manifestation of the molecular circadian clock, a highly conserved network that maintains a near 24-hour rhythm even in the absence of light. In mammals, light signals are transmitted via the superchiasmatic nucleus (SCN) in the hypothalamus to synchronize peripheral clocks and coordinate physiological functions with the organism’s active period. This collection of reviews, curated by Amita Sehgal, considers the critical role of the circadian system in human health. Technology, work, and social obligations can disrupt optimal sleep and wake schedules, leaving humans vulnerable to diseases affecting the heart, brain, metabolism, and more. Sleep disorders as well as normal variations in human chronotype may exacerbate circadian disruptions, with profound consequences. These reviews emphasize that ongoing efforts to understand the complexities of human circadian rhythm will be essential for developing chronotherapies and other circadian-based interventions.
Published October 2021
This collection of reviews focuses on the gut-brain axis, highlighting crosstalk between the gastrointestinal tract and the enteric and central nervous systems. While the enteric nervous system can exert independent control over the gut, multi-directional communication with the central nervous system, as well as intestinal epithelial, stromal, immune, and enteroendocrine cells can result in wide-ranging influences on health and disease. The gut microbiome and its metabolites add further complexity to this intricate interactive network. Reviews in this series take a critical approach to describing the role of gut-brain connections in conditions affecting both gut and brain, with the common goal of illuminating the importance of the central and enteric nervous system interface in disease pathogenesis and identifying nodes that offer therapeutic potential.
Published July 2021
Cancer cells in a solid tumor are supported by vasculature, extracellular matrix, nerves, and an immunological milieu collectively known as the tumor microenvironment. Elements within the tumor microenvironment can act in a coordinated fashion to support tumor growth, immune evasion, and metastasis. In this series, reviews curated by Series Editor Andrew Ewald highlight the tumor microenvironment’s complex effects in cancer, describing its modulation of immune cells and the tumor stroma as well as its role in disseminating metastases.
Published March 2021
Diabetes results from a disturbance in regulating blood sugar. In type 1 diabetes, an autoimmune response triggers the destruction of pancreatic beta cells, which produce insulin that controls glucose uptake in cells, whereas type 2 diabetes is caused by impairments in making or responding to insulin. The discovery of insulin in 1921 led to lifesaving therapy for type 1 diabetes and ushered in the era of modern medicine based on understanding the molecular basis of disease. Curated by JCI’s editor in chief, Rexford S. Ahima, the reviews in this series explore a wide range of topics in diabetes, from insulin’s discovery, insulin secretion and signaling, type 1 diabetes, monogenic diabetes, and insulin resistance syndromes, as well as pharmacological and dietary treatment options for type 2 diabetes. Cumulatively, these reviews highlight the genetic and molecular mechanisms underlying diabetes pathogenesis and discuss existing and potential new therapeutic approaches to treat and manage diabetes.
Published January 2021