Maintaining adequate oxygen levels in the organs and tissues of multicellular organisms is essential to preserving cellular metabolism and bioenergetics. When oxygen levels fall below normal physiological levels, hypoxia signaling pathways trigger physiological changes meant to evoke adaptive responses at organismal, tissue, and cellular levels. Hypoxia-inducible factors (HIFs) are positioned at the crux of these oxygen-sensing mechanisms, regulating a multitude of transcriptional programs that control angiogenesis, metabolism, immune function, erythropoiesis, and more. In this issue, a review series created by JCI’s deputy editor Gregg Semenza highlights how HIFs contribute to the pathogenesis and treatment of human disease. The reviews describe the hypoxic conditions that drive or exacerbate pathophysiology in diseases ranging from pulmonary hypertension to cancer. Moreover, they highlight HIF-targeting strategies in preclinical and clinical development, discussing their potential to improve the therapeutic outcomes in these diseases.
Latency describes the persistence of a microorganism within its host in the absence of clinical symptoms of disease. Both microorganism and host benefit from induction of latency: the microorganism establishes a stable environment that facilitates survival, and the host avoids progressive damage and disease. Latent states have been observed in bacterial, viral, fungal, and parasitic infectious diseases, though the mechanisms differ within each microorganism and host pair. In this issue, a Review Series on Latency in Infectious Disease explores the different strategies that various microorganisms use to achieve latency. Conceptualized by JCI’s Deputy Editor Arturo Casadevall, the series highlights the latency mechanisms employed by herpesviruses, HIV, Cryptococcus neoformans, and Toxoplasma gondii. In addition to describing mechanisms, the reviews outline the detrimental effects of latent disease and recent progress toward treatment and eradication.
Published July 2020
Immunotherapeutic strategies leveraging the immune system’s antitumor activity have become a mainstay of cancer treatment. Strategies including antibody-directed approaches, stem cell transplantation, immunomodulatory drugs, immune checkpoint inhibitors, CAR T cells, and vaccines have demonstrated particular success in controlling and even eradicating hematological cancers. This Review Series, developed by JCI’s associate editor Leo Luznik, discusses ongoing progress in immunotherapeutic targeting of hematological cancers. Reviews will address the state-of-the-art in immunotherapies for acute myeloid leukemia, multiple myeloma, and lymphoma and highlight recent successes and challenges in clinical trials for these diseases; take a detailed look at recent developments in CAR T therapies for B cell malignancies; and describe how personalized antigen targeting can be applied to immunotherapeutic treatment of blood malignancies.
Published April 2020
The healthcare industry generates massive amounts of data originating from a variety of sources, among them patient health records, pharmacies, clinical trials, insurance providers, regulatory bodies, hospitals and clinics, and wearable devices and sensors. Advances in data processing, analysis, and deep learning techniques have made it possible to leverage this wealth of healthcare data to optimize patient care. In this series, reviews discuss the potential for large-scale datasets to provide valuable insights that help personalize therapies, diagnose and understand rare diseases, optimize clinical trial design, facilitate drug discovery and development, reduce healthcare costs, and more. The reviews also discuss the limitations of existing analysis methods, asserting that analyses of large-scale datasets can complement traditional preclinical and clinical research. As healthcare data increases in volume and complexity, so does its potential to transform medical practice and research.
Published February 2020
Obesity often occurs with a quintessential array of metabolic abnormalities: elevations in blood pressure, visceral fat, and circulating blood lipids, and, importantly, insulin resistance. Together, this constellation of conditions constitutes the metabolic syndrome and forecasts an individual’s increased risk of developing cardiovascular diseases and type 2 diabetes. Although metabolic syndrome presents as dysfunction across multiple tissues, its onset stems from pathological increases in adipose tissue. The 9 review in this series, conceptualized by series editor Philipp Scherer, delve into the complex biology underlying the metabolic syndrome. These reviews address adipocyte and beta cell dysfunction in the metabolic syndrome; the functions of adipose tissue fibrosis, the microbiome, and exosomal communication in obesity; and the concepts we use to define metabolic health.
Published October 2019
The immune system mounts a rapid inflammatory response to injury to mobilize cells and molecular pathways that promote hemostasis and prevent infection, but this acute response is only the first phase of recovery. Wound repair and inflammation-resolving processes are essential to recovering homeostasis in the aftermath of an injury: inefficient healing or prolonged inflammation can drive chronic dysfunction in the affected tissue. The Reparative Immunology series highlights the immune system’s contributions to these critical repair processes, from the roles of T cells, macrophages, neutrophils, and innate lymphoid cells in physiological repair to the influence of cytokine signaling, immunometabolism, and epigenetic reprogramming on pathological outcomes of injury. Together, these reviews emphasize the complexity of the immune environment in injured tissue and indicate numerous potential opportunities to intervene in dysfunctional wound-healing.
Published July 2019
The increasing prevalence of allergies worldwide has spurred numerous efforts to better understand risk factors and mechanisms underlying these potentially life-threatening immune responses. Coordinated by Series Editor Kari Nadeau, these reviews address our evolving understanding of the shared and distinct mechanisms underlying allergic diseases of the skin, respiratory system, and gastrointestinal tract. In topics ranging from the molecular and cellular basis of allergy to the influence of the central nervous system, microbiome, and environment, leaders in the field highlight major insights into allergic responses as well as new concepts in treating and preventing allergy.
Published April 2019
Heritable germline mutations are estimated to drive 10% of all cancers, which can manifest as pediatric as well as adult diseases. This series, curated by Agata Smogorzewska and JCI Associate Editor Mary Armanios, unravels how the biology and genetics underlying familial cancer predisposition syndromes informs understanding of cancer etiology and biology. Reviews focus on cancer-driving mutations in transcription factors, in developmental and metabolic signals, and in pathways that control genetic stability and provide insights linking mechanistic studies with ongoing clinical research. Enhanced understanding of the biological basis for these familial cancers may inform the treatment of cancers driven by both germline and somatic mutations.
Published February 2019
Mitochondria transform nutrients and oxygen into chemical energy that powers a multitude of cellular functions. While mitochondrial aerobic glycolysis generates the majority of a cell’s ATP, its byproducts also have wide-ranging influences on cellular health and longevity. This review series, edited by Dr. Michael Sack, focuses on the many contributions of mitochondria to disease and aging. The reviews highlight evidence linking altered mitochondrial metabolism and oxidative stress to a range of pathophysiological phenomena: inflammation and immune dysfunction, heart failure, cancer development, metabolic disease, and more. In many diseases and conditions, mitochondrial dysfunction is considered the tipping point toward pathological progression. However, as these reviews discuss, therapeutic targeting of mitochondria may be a powerful strategy to subvert disease and aging processes.
Published August 2018
Infection and injury induce self-limited inflammatory responses that mount a defense against pathogens and initiate activities that expedite recovery. However, the benefits of inflammation recede when these responses fail to resolve in a timely manner. This series features a family of specialized lipid mediators that regulate the resolution of inflammation. The reviews, curated by Charles Serhan, highlight the wide-ranging involvement of these bioactive lipids in health and disease. Work by Serhan and others has revealed that the resolvin, protectin, and maresin families of pro-resolving mediators act as immunoresolvents and represent promising alternatives to immunosuppressant and anti-inflammatory therapies. Other lipid mediators, including leukotrienes, ceramides, and sphingolipids have roles in cancer, cardiovascular disease, and aging. Our evolving understanding of lipid mediators in regulating inflammation and disease pathogenesis presents promising opportunities for new therapeutic strategies.
Published July 2018