Lipid Metabolism and Cardiometabolic Disease

Metabolic diseases such as diabetes, steatohepatitis, and coronary artery disease result from the delivery of nutrients that exceed a tissue’s energetic needs or storage capacity. The excess nutrients give rise to deleterious lipid species that impair cellular function. Summers and colleagues found that ceramides, a class of sphingolipids, alter the metabolism of liver and adipose tissue in a way that gives rise to cardiometabolic disease. Continue reading → Lipid Metabolism and Cardiometabolic Disease

Causes of Type 1 Diabetes

More than 1 million Americans suffer from Type 1 diabetes, which occurs when a patient’s immune T cells attack their pancreas. Understanding why this occurs is key to developing treatments that target the cause and not just the symptoms of diabetes. Continue reading → Causes of Type 1 Diabetes

How Cells Choose to Create Energy

To supply their energy needs, cells typically choose between utilizing glucose in the cytoplasm (aerobic glycolysis and lactic acid fermentation) or “burning” pyruvate in the mitochondria (mitochondrial carbohydrate oxidation). Although this is arguably the most fundamental metabolic decision that cells make, before 2012 it was not clear how cells import pyruvate into mitochondria to fuel ATP production. Continue reading → How Cells Choose to Create Energy

Architecture of the Inner Ear

Normal hearing is dependent upon a highly specialized structure in the inner ear called the tectorial membrane. How this precisely organized extracellular matrix is assembled had been unknown. However, Park and colleagues showed the inner ear membrane anchors to the cell surface during development and grows one layer at a time. Continue reading → Architecture of the Inner Ear

Gene Expression and Health Risks

An important area of research involves learning how gene expression influences health and disease risks. The parts of the genome that regulate gene expression are cis-regulatory elements. Gregg and colleagues took an unusual approach to discover these cis-regulatory elements by analyzing the genomes of species that evolved disease resistance “superpowers”. Continue reading → Gene Expression and Health Risks

How Microbes Make Drug-like Molecules

Many life-saving drugs come from natural sources such as microbes. Learning how host organisms produce these drugs is an area of intense interest because scientists could exploit the pathways to produce more and better drug variants. Schmidt and colleagues have elucidated the mechanisms by which microbes produce one class of drug-like molecules, the Ribosomally-synthesized and Post-translationally modified Peptides (RiPPs). Continue reading → How Microbes Make Drug-like Molecules

An EHR Clinical Support App for Monitoring Bilirubin Levels

Electronic health records (EHR) are a rich source of clinical and research data, but clinicians and researchers often cannot access this information efficiently. The Department of Biomedical Informatics has developed the ReImagineEHR initiative to improve the functionality of electronic health record systems. Continue reading → An EHR Clinical Support App for Monitoring Bilirubin Levels

Drug-Free Macromolecular Therapeutics

Monoclonal antibody therapy has numerous benefits but can lack efficacy, often because monovalent binding of antibodies to specific receptors fails to translate into an active response. The Kopeček laboratory has built on their track record in polymeric drug delivery to develop a novel approach to therapeutic design, termed “Drug-Free Macromolecular Therapeutics (DFMT)”. Continue reading → Drug-Free Macromolecular Therapeutics

Analyzing Human Pedigrees to Advance Genetics and Health

Well curated human pedigrees like the iconic pedigrees maintained by the Centre d’Etude du Polymorphism Humain (CEPH) provide an invaluable resource for fundamental discoveries in human genetics and health. The CEPH collection includes families collected by R. White (Utah), J. Dausset (French), J. Gusella (Venezuelan), and J. Egeland (Amish). Continue reading → Analyzing Human Pedigrees to Advance Genetics and Health

Cellular Origins of Pancreatic Cancer

Our pancreas has two main functions, endocrine control of blood sugar and exocrine production of the enzymes that digest our food. These enzymes are synthesized by pancreatic acinar cells and transported to the intestine through a network of pancreatic duct cells. Pancreatic cancer, the third deadliest cancer in the U.S., was previously assumed, based on histology and gene expression, to arise from duct cells. Continue reading → Cellular Origins of Pancreatic Cancer

Biological Consequences of Reduced Energy Flux and Inefficient Energy Generation

Energy transfer processes are never perfectly efficient. Funai and colleagues have discovered that the degree of inefficiency in cellular energy exchange, particularly during oxidative phosphorylation, has important biological implications. Continue reading → Biological Consequences of Reduced Energy Flux and Inefficient Energy Generation

Signaling Pathways That Underlie Heart Disease

Diseases affecting heart function exact an enormous toll on human health, but many of the genetic and molecular mechanisms underlying heart disease remain unknown. Yost and colleagues discovered novel roles for the same developmental signaling pathway in two seemingly unrelated sources of cardiac dysfunction: adult heart failure and embryonic heart malformation. Continue reading → Signaling Pathways That Underlie Heart Disease

Neuronal Circuits that Modulate Pain and Defensive Responses

Understanding pain-processing mechanisms and the neural circuits involved is central to developing new therapeutic strategies for the treatment of pain. The Douglass lab investigated brain regions that modulate behavioral responses to noxious stimuli in zebrafish. Continue reading → Neuronal Circuits that Modulate Pain and Defensive Responses

Generation and Treatment of Antibiotic Resistance

Antibiotics are responsible for the most significant increase in lifespan in human history. However, microbes are becoming resistant to antibiotics at an alarming rate. The Mulvey lab found that microbes within a single colonized site, such as the human bladder, can pass antibiotic resistance genes back and forth, propagating resistance as the infecting microbes evolve in response to serial antibiotic treatment. Continue reading → Generation and Treatment of Antibiotic Resistance

Structures and Mechanisms of Protein Remodeling Machines

When a cellular protein has done its job or lost its utility, it should be removed, recycled, or remodeled. These tasks are performed by members of the ubiquitous family of AAA ATPases (ATPases associated with diverse cellular activities) that convert the energy of ATP hydrolysis into mechanical forces that can unfold protein aggregates, degrade unwanted proteins, and remodel protein complexes. Continue reading → Structures and Mechanisms of Protein Remodeling Machines

Pinpointing Environmental Sources of Pediatric Asthma

Identifying the sources that trigger pediatric asthma is critical for successful therapeutic interventions. The University scientists collaborated with the families to develop a biomedical informatics platform to crowdsource and link air quality data with personal health monitoring data and other data resources to pinpoint environmental causes of patient symptoms. Continue reading → Pinpointing Environmental Sources of Pediatric Asthma

Commensal Microbes That Help Prevent Metabolic Disease

Our intestines are colonized by a vast consortium of bacteria, viruses, and fungi that we now know have essential influences on gut health. Research in the Round lab has recently shown that intestinal antibody responses select for specific organisms within the gut that prevent metabolic disease by limiting fat absorption within the intestine. Continue reading → Commensal Microbes That Help Prevent Metabolic Disease

Improved Prognostic Testing for Patients with Triple Negative Breast Cancer

Approximately 40% of patients with stage I-III triple-negative breast cancer (TNBC) have recurrences after standard treatment, whereas the remaining 60% experience long-term disease-free survival. However, there are currently no clinical tests to assess the risk of recurrence in TNBC patients. Continue reading → Improved Prognostic Testing for Patients with Triple Negative Breast Cancer

Developing New Chemical Reactions that Can Be Performed in Living Cells

The development of bioorthogonal chemical reactions—chemical reactions that can be conducted in living cells—has been one of the most significant areas of advancement in chemistry in recent years. Franzini and colleagues have developed a series of highly efficient chemical reactions, termed “dissociative bioorthogonal reactions”, that do just that. Continue reading → Developing New Chemical Reactions that Can Be Performed in Living Cells

The Role of Cholesterol in Activating a Key Cellular Signaling Pathway

Hedgehog signaling promotes embryonic development and, when aberrant, can lead to malignancies. The seven-transmembrane transducer Smoothened (SMO) occupies a key node in this pathway and is activated by cholesterol. Continue reading → The Role of Cholesterol in Activating a Key Cellular Signaling Pathway

Impact of Policy on VA Healthcare Utilization

Significant internal and external changes have affected the utilization of healthcare services in the Department of Veterans Affairs (VA). The VA is the largest integrated healthcare system in the U.S., with 9 million enrollees and 6 million users per year. Continue reading → Impact of Policy on VA Healthcare Utilization

MicroRNA Regulation of Inflammation and Immunity

MicroRNAs provide a crucial level of control for cell development and function through their post-transcriptional regulation of gene expression. Their importance is highlighted by their diverse functions in a range of cell types, including immune cells. Continue reading → MicroRNA Regulation of Inflammation and Immunity