Mechanisms of Circulatory Abnormalities and Fatigue in Patients with Cardiovascular Diseases

Markus Amann, PhD, and colleagues recently discovered that both heart failure and hypertension impair an important neurocirculatory control mechanism in humans—specifically, a reflex loop mediated by neural feedback from muscles to the central nervous system. This impairment results in excessive sympathetic nervous system activity, and largely accounts for the circulatory abnormalities observed during physical activities. Continue reading → Mechanisms of Circulatory Abnormalities and Fatigue in Patients with Cardiovascular Diseases

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

Bone-Anchored Devices that Permanently Pass Through the Skin to Maximize Amputee Function

A common orthopedic approach to recreating damaged joints is to securely attach a metal implant to the patient’s own bone, a process known as osseointegration. Our research explores a new approach by engineering percutaneous osseointegration devices, in which the metal implant that pass permanently through the skin and permit connection to an external prosthetic limb when desired. The connection can not only be accomplished easily as needed; it also improves the function of the prosthesis. Continue reading → Bone-Anchored Devices that Permanently Pass Through the Skin to Maximize Amputee Function

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

Finding New Ways to Treat Kidney Disease

Research in the Kohan lab, using genetically engineered mice, has helped identify the peptide, endothelin-1, and its receptor, ETA, as key regulators of blood pressure and kidney function in health. They have also helped determine that kidney ET-1 production is increased in many kidney diseases and, via activation of ETA receptors on most kidney cell types, leads to inflammation, scarring and decreased kidney function. Continue reading → Finding New Ways to Treat Kidney Disease

Combination Therapy for Treatment-Resistant Pancreatic Cancer

McMahon and colleagues reported that simultaneous combined inhibition of MEK plus autophagy displayed synergistic anti-proliferative effects against cultured pancreatic cancer cell lines and promoted regression of xenografted patient-derived pancreatic tumors in mice. Continue reading → Combination Therapy for Treatment-Resistant Pancreatic Cancer