The term autophagy, or “self-eating”, refers to the processes by which cells deliver cytoplasmic constituents to lysosomes for degradation. Autophagy provides biosynthetic precursors and energy sources to sustain metabolism and cell growth and prevent the accumulation of toxic components. These processes are invoked in response to stressors, including changing nutrient conditions, damage to organelles, intracellular pathogens, and accumulation of reactive oxygen species, among others, in order to maintain cellular homeostasis. Autophagy becomes insufficient with age and is perturbed in multiple disease states; consequently, pathogenic aberrations in autophagy have emerged as a major focus in the development of novel therapeutic strategies. Reviews in this series detail specific autophagic mechanisms; the role of autophagy in cardiovascular disease, cancer, neurodegeneration, lifespan, and the immune system; and methods to develop autophagy-centered therapeutic modalities.
Published January 2015
The human gastrointestinal tract harbors approximately one hundred trillion microbial cells, collectively known as the gut microbiome. We have been aware of these friendly bacteria for around a century, but we are only now beginning to appreciate their influence in multiple aspects of human physiology and disease. Our understanding of the gut microbiome is constantly evolving and is currently being aided by new technologies and approaches that combine ecological principles with biomedical techniques. These new studies take into account both the pathological and commensal aspects of the microbes that inhabit our bodies. Reviews in this series explore how perturbation of the microbiome not only contributes to disease, but also helps to reveal its function; the impact of the microbiome on the metabolism of therapeutics and dietary nutrients; the contributions of commensal bacteria to disease, including cancer and cardiovascular disease; and the role of the microbiome in the development and maintenance of the immune system.
Published October 2014
Nephrology encompasses the study of normal kidney function, kidney disease, and kidney replacement therapy, including kidney transplantation and dialysis. Kidney diseases are a serious public health problem, with nearly 12% of American adults suffering from chronic kidney disease (CKD). Importantly, kidney dysfunction is associated with the increasingly common conditions of obesity, diabetes, and hypertension. Recent technological advances, including genetic and epigenetic screens, metabolic profiling, new model systems, and the use of kidney biopsies for diagnosis and treatment, have created new avenues for the study of kidney pathology. Reviews in this series provide a survey of kidney pathogenesis, including hypertension, diabetic kidney disease, IgA nephropathy, idiopathic membranous nephropathy, acute kidney injury, fibrosis, and mechanisms mediating graft failure after transplantation.
Published June 2014
Significant progress in the last 15 years has transformed the field of lymphatic vasculature research into a boom area. The relatively recent identification of specific growth factors and molecular markers that distinguish endothelial cells of the lymphatic and blood vasculature lineages were pivotal for this development. Given the almost ubiquitous distribution of lymphatic vessels in most organs, it is not surprising that this type of vasculature is actively or passively involved in a large number of human diseases. The reviews in this series aim to describe a number of emerging areas in lymphatic biology, including mechanisms that mediate lymphangiogenesis, the development of mammalian lymphatic vasculature, the genetics of lymphatic anomalies, new technologies for studying the lymphatic vasculature, and the role of lymphatics in disease, including lymphedema and cancer, and physiological processes, such as inflammation and immunity. Cover image credit: K.Pichler/CeMM/MedUni Wien/Josephinum (www.josephinum.ac.at).
Published March 2014
A key characteristic of cancer cells is the presence of genome alterations, including changes in epigenetic modifications that can profoundly impact gene expression and cellular function. Regulators of DNA methylation and histone modification can thus be considered as potential therapeutic targets in oncology. In recent years, DNA methyltransferase inhibitors and histone deacetylase inhibitors have shown efficacy in treating some hematological malignancies. Intense efforts are underway to develop the next generation of inhibitors, including targeting additional epigenetic regulators, and further to test treatment of solid tumors. The reviews in this series explore advances in cancer epigenetics driven by high-throughput sequencing studies, the clinical use of DNA methyltransferase inhibitors, the development of inhibitors targeting histone modifying enzymes, biomarkers of drug efficacy, and aging-related changes in the epigenome. In his overview, series editor Peter Jones highlights ongoing basic and clinical efforts as well as future challenges in translating epigenetic research to patient therapy.
Published January 2014
An association between cancer and altered cellular metabolism has been known for decades, and clinically this aspect of tumor biology is exploited by imaging techniques that rely on the uptake of labeled glucose analogues to identify tumors. Following the discovery of oncogenic mutations in several metabolic enzymes, there has been a resurgence of interest in recent years on the role that altered metabolism plays in tumor development and maintenance. The reviews in this series address many key facets of cancer metabolism, including the role of isocitrate dehydrogenase (IDH) mutations and oncometabolites, the link between tumor hypoxia and metabolism, as well as lactate and glucose metabolism in tumors. Further, these reviews collectively explore emerging therapeutic and imaging options that target metabolic pathways in cancer. Image credit, Drs. Changho Choi and Elizabeth Maher.
Published September 2013
The liver plays vital roles in digestion, metabolism, and detoxification. Remarkably, the adult liver has a unique ability to regenerate, with a capacity to regenerate even after two-thirds of the organ is removed by partial hepatectomy. The reviews in this series explore the roles of hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells, and hepatic stem/progenitor cells in development, repair, and pathogenesis. Improved understanding of the cellular process underlying development and regeneration may provide important insights into liver injury caused by disease and aberrant cellular replication in liver cancers. Image credit: Dr. Kenichiro Furuyama.
Published May 2013
Aging is an inevitable facet of life. However, research into the molecular mechanisms of aging suggests potential targets that could be therapeutically modified to slow the aging process and increase the span of healthy living. The articles in this series explore selected cellular mechanisms of aging and their link to age-related clinical conditions. These mechanisms include short telomeres, the induction of the senescence-associated secretory phenotype (SASP) in systemic aging, sirtuin regulation of metabolism and aging-associated diseases, mitochondrial metabolism in aging, the mTOR signaling pathway and longevity, aging and immune system function, and aging-associated changes in pancreatic β-cells.
Published March 2013
Despite incredible progress in cardiology research, cardiovascular disease remains the leading cause of death in industrialized nations. The reviews in this series explore selected areas of cardiovascular research that show promising translational potential. Areas of interest include therapeutic antagomirs targeting cardiac microRNAs, the genetic basis of cardiomyopathies and cardiac arrhythmias, the role of chronic inflammation in atherosclerosis, S-nitrosylation in vasodilatation, as well as emerging approaches to treat heart failure, such as gene therapy, stem cell regeneration, therapeutics that restore normal calcium cycling, and interventions to reduce reperfusion injury following myocardial infarction. Advances stemming from these ongoing research efforts may soon be poised to make an impact on the clinical management of cardiovascular disease. Image credit: BSIP / Science Source.
Published January 2013
Cancers derived from lymphoid cells, including B cell and T cell lineages, often exhibit aberrant processes of lymphoid differentiation or activation, resulting in a broad spectrum of diverse and complex lymphomas and leukemias. The reviews in this series focus on recent progress in selected lymphoid malignancies, with an emphasis on the molecular mechanisms and genetic alterations that drive oncogenesis, including new mutations identified by genome-wide analyses. These newly identified genes are improving our mechanistic understanding of how these cancers develop and progress, and provide new opportunities for therapeutic intervention. Cover image credit: Aaron Polliack / Photo Researchers, Inc.
Published October 2012