Research News

TDP-43 in Neurodegenerative Diseases
May 15, 2017

Yuna Ayala, Ph.D., Assistant Professor of Biochemistry, published a paper in The Journal of Biological Chemistry detailing studies on TAR DNA-ginding Protein 43 (TDP-43) and its role in neurodegenerative diseases, such as amytrophic lateral sclerosis (ALS).

TDP-43 regulates gene expression through RNA processing, and is essential for development and survival. It also forms intracellular aggregates in ALS and some other neurological diseases, resulting in loss of function of normal TDP-43. The researchers found that double phosphorylation of TDP-43 by MEK, a kinase in the MAPK/ERK signaling pathway that is activated by cellular heat shock response (HSR), did not aggregate and showed decreased splicing activity. These results uncovered a previously unknown mechanism of regulation for TDP-43, which could lead to new strategies to treat aggregation as well as new roles of TDP-43 in cellular metabolism.

For more information, read the full article in Newslink.

Heart Failure Editorial in NEJM
April 19, 2017

Paul Hauptman, M.D., of the Department of Internal Medicine-Cardiology, published an editorial in the New England Journal of Medicine reviewing the results of the Trail of Ularitide Efficacy and Safety in Acute Heart Failure (TRUE-AHF) study. The purpose of the study was to determine the safety and effectiveness of a new synthetic drug, “ularitide”, in treating patients with acute decompensated heart failure (ADHF).

ADHF is a worsening of heart failure symptoms such as difficulty breathing, fatigue, and swelling of legs or feet. The trial sought to determine if a single treatment with ularitide would improve symptoms and if rapid treatment would improve long-term survival. However, it was found that the effects of treatment were limited and short-lived.

For more information, read the full article in Newslink.

REV-ERB Regulation of LDL Cholesterol
March 10, 2017

Thomas Burris, Ph.D., Chair and Professor of Pharmacology and Physiology, published a paper in Biochemical Pharmacology on studies of the nuclear receptor, REV-ERB, and its role in regulation of LDL cholesterol.

Researchers used a mouse model to study the effects of a REV-ERB agonist, SR9009, and showed that it reduced plasma cholesterol in wild-type and LDLR null mice. They also showed that mice with no expression of REV-ERB has increased plasma LDL. Researchers showed that REV-ERB binds to the majority of genes related to cholersterol biosynthesis and suppresses expression of these genes, making it a potential target for treatment of LDL levels in human disease.

For more information, read the full article in Newslink.

Dendritic Cells Conduct Immune Cell Symphony
November 4, 2016

Daniel Hawiger, M.D., Ph.D., Associate Professor of Molecular Microbiology and Immunology, published a paper in Immunity reporting recent research on special immune system cells, dendritic cells, which direct other lymphocytes in the immune system what to do and how to do it. Dendritic cells train T cells how to recognize an infection and fight it, or how to maintain tolerance for the body’s own cells.

This recent paper details the mechanism by which tolerance is achieved and how dendritic cells play a role in activation of T cells.

For more information, read the full article in Newslink.

A New Vaccine for Chagas Disease
November 1, 2016

Daniel Hoft, M.D., Ph.D., Professor of Infectious Diseases, and Catherine Cai, M.D./Ph.D. student, recently published a paper in PLoS Pathogens detailing their findings on Th17 cells, a subset of white blood cells that provide significant protection against Trypanosoma cruzi, the protozoan parasite that causes Chagas disease.

Th17 cells were not formerly thought to play a role in immune function. However, the researchers found that these cells directly and indirectly help boost immunity to T. cruzi, opening the door to development of a vaccine for Chagas disease and possibly other treatment options. This work could also lead to vaccines and treatments for similar intracellular pathogens, such as tuberculosis and HIV.

For more information, read the full article in Newslink.

SLU Launches Trial for Zika Vaccine
June 28, 2016

Sarah George, M.D., Associate Professor of Infectious Diseases, is PI on a clinical trial to test a Zika virus vaccine. The trial will be conducted at the Center for Vaccine Development at SLU in partnership with a research site in Puerto Rico.

Zika is a flavivirus spread by the Aedes mosquito, but can be transmitted sexually as well. Babies born to women who contracted the virus during pregnancy are often born with complications, including microcephaly and vision deficits. Developing a vaccine that can be given early in life could help protect future generations from the devastating effects of this virus.

For more information, read the full article in Newslink.

For an update on the clinical trial for the ZPIV investigational vaccine, see the November story in Newslink.

Teague Publishes Findings to Improve Cancer Studies
June 2, 2016

Ryan Teague, Ph.D., Associate Professor of Molecular Microbiology and Immunology, recently published a Feature Review article in the June 2016 issue of Trends in Immunology detailing ways in which researchers could better design cancer studies using animal models.

Because most cancer patients are elderly, studies on immunotherapy and cancer should include older mice, since the immune systems grows less reponsive with age. In addition, using obese mice in these types of studies would also make the results more relevant to real patients, since obesity and different microbe populations in the gut can affect how well immune therapies might work.

For more information, read the full article in Newslink.

New Treatment for Pancreatic Fibrosis
April 14, 2016

Barbara Ulmasov, Ph.D., Associate Research Professor of Gastroenterology, recently published a paper in Cellular and Molecular Gastroenterology and Hepatology reporting her findings on a possible new treatment for pancreatic fibrosis. The study was done in a mouse model of the disease.

Fibrosis, or scarring, of the pancreas occurs during chronic pancreatitis, a progressive disease causing chronic pain, malnutrition, and diarrhea. Their research found that cytokine transforming growth factor beta (TGFB) activated cells in the pancreas that regulate the development of pancreatitis. The researchers created a mouse model of pancreatic fibrosis and then treated the mice with an integrin inhibitor, which blocks the action of TGFB. The mice treated with the integrin inhibitor showed less scarring and halted the progress of the fibrosis. These studies showed that a treatment for a prevalent disease may be available, not only halting the fibrosis, but perhaps allowing healing of the pancreas cells as well.

For more information, read the full article in Newslink.

Vindigni Lab Studies DNA Stress
March 31, 2016

Alessandro Vindigni, Ph.D., Professor of Biochemistry, recently published a paper in Nature Structural & Molecular Biology detailing his studies on how cells manage replication stress, allowing them to overcome DNA lesions or replication-fork obstacles in order to produce viable daughter cells and transmission of the genetic code.

Cell stressors can include exposure to free radicals, UV radiation, X-rays, or chemicals, and can cause DNA lesions as often as 100,000 times per day. These lesions block the progress of replication forks during DNA replication. Cells use several methods to overcome these stressors: fork repriming, fork reversal, fork degradation and backtracking, replication-fork breakage, and replisome dynamics during replication-fork restart. Each method allows the cell to repair the obstacle and avoid passing on genetic mutations or losing genetic information. Understanding these cellular mechanisms can help scientists develop preventions and treatments for diseases, including cancer.

For more information, read the full article in Newslink. Dr. Vindigni was also interviewed about his research on the Fox2News morning show.

SBGrid Streamlines Data Analysis
March 22, 2016

Enrico Di Cera, M.D., Professor and Chairman of Biochemistry, is one of the authors on a paper recently published in Nature Communications. Researchers from institutions all over the world were involved in the creation of the Structural Biology Grid Consortium, in which experimental data sets and raw data can be uploaded and made available to all researchers for analysis and verification of crystallographic structures.

The Consortium will manage raw, experimental data sets, curate and support the data collection process, establish a publication system for data sets, and integrate storage resources of multiple researchers and institutions. It is a true global effort, giving researchers unprecedented access to data and data analysis resources.

For more information, read the full article in Newslink.

RSV Intasome Structure Solved
February 29, 2016

Duane Grandgenett, Ph.D., Professor of the Institute for Molecular Virology, along with colleagues from the University of Minnesota and Cornell University, recently published a paper in Nature reporting the crystal structure of the Rous sarcoma virus (RSV) intasome.

The intasome is involved in integration of the virus into the host genome via integrase and is an essential step in the viral life cycle. The structure of the RSV instasome is very similar to that of HIV, which could aid in understanding integration of HIV and other retroviruses. Dr. Grandgenett discovered integrase in 1978 and this enzyme is now the basis for the safe and effective class of drugs used to treat HIV infection.

For more information, read the full article in Newslink.

Opioid Use and Depression
January 21, 2016

Jeffrey Scherrer, Ph.D., Associate Professor of Family and Community Medicine, published an article on opioid use and depression. The study entitled “Prescription Opioid Duration, Dose, and Increased Risk of Depression in 3 Large Patient Populations” was published in the January/February 2016 issue of the Annals of Family Medicine. The article reports his group’s findings on the link between length of use of opioid pain medications and onset of new depression symptoms.

The researchers collected patient data from several health systems from 2000-2012. After analyzing the data, they found that new-onset depression resulted from length of use of opioids and was not related to dosage. The findings were consistent even though the patient demographics and characteristics from the health systems were very different.

For more information, read the full article in Newslink.

Possible New Treatment for Autism
December 8, 2015

Thomas Burris, Ph.D., Professor and Chair of Pharmacology and Physiology, recently published an article in ACS Chemical Neuroscience reporting studies to treat the underlying pathology of autism spectrum disorder (ASD).

The researchers identified a nuclear receptor, retinoic acid receptor-related orphan receptor α (RORα) that has reduced expression in many individuals with ASD. They developed a compound, SR1078, which reduced ASD-related behaviors, such as overgrooming, in mice and also increased expression of RORα target genes in mice and in a neuroblastoma cell line. These genes are underexpressed in autistic brains. These results indicate that SR1078 may be a viable treatment for ASD.

For more information, read the full article in Newslink.

Fighting Viruses in Immunosuppressed Patients
September 2, 2015

William Wold, Ph.D., Professor and Chair of Molecular Microbiology & Immunology, recently published an article in PLoS Pathogens reporting studies to prevent a group of common viruses, called adenoviruses, from causing sickness in immunosuppressed patients. While these viruses are generally not serious for most people, they can be life-threatening for patients undergoing immunosuppressive treatments.

Researchers found that Type I interferon is needed to fight adenvirus infection and multiplication. They used a genetically modified Syrian hamster model, which had the gene controlling the interferon pathway, STAT2, knocked out, and compared the amount of virus present in the knockout hamsters with that present in wild-type hamsters. The knockout hamsters had 100 to 1000 times more virus, thus showing how important interferon is in fighting adenovirus infection.

For more information, read the full article in Newslink.

Fighting the Warburg Effect in Cancer Cells
July 7, 2015

Thomas Burris, Ph.D., Professor and Chair of Pharmacological and Physiological Science, recently published an article in Cancer Cell. The article details his research on stopping cancer cell growth by targeting the energy source that tumors use to grow.

Cancer cells almost always prefer glucose as their energy source and use glycolysis, also called the Warburg effect, to reproduce. The researchers found that a drug they developed, SR9243, can inhibit the Warburg effect by inducing the nuclear receptor, liver-X-receptor (LXR), which regulates the expression of key glycolytic and lipogenic genes, thus disrupting key oncogenic metabolic pathways. The drug also induced apoptosis in tumor cells with few side effects.

So far, SR9243 has been tested in cultured cancer cells and in some animal models with promising results for some cancers, including lung, prostate, and colorectal cancer. There is also evidence that SR9243 could increase the effectiveness of existing chemotherapy drugs when they are used in combination.

For more information, read the full article in Newslink.

Increasing Bone Formation in Osteoporosis
May 29, 2015

Rajeev Aurora, Ph.D., Associate Professor of Molecular Microbiology and Immunology, published an article in the May 2015 issue of the Journal of Bone and Mineral Research. The article details his research on the causes of bone resorption and formation in osteoporosis.

The group showed that the protein, RANKL (receptor-activator of NF-kappa B ligand), stimulates osteoclasts and induces a pathway of bone resorption in high doses, causing bone disorders such as osteoporosis, periodontitis, and rheumatoid arthritis. However, they found that when RANKL was given to mice in small doses, it had the opposite effect of suppressing osteoclast activity and increasing bone formation. Their research has potential clinical significance in developing new treatments for bone disorders.

Treatment for Chronic Pain
April 24, 2015

Daniela Salvemini, Ph.D., Professor of Pharmacological and Physiological Science, recently published an article in Journal of Neuroscience reporting studies to block chronic neuropathic pain. The studies were done in collaboration with researchers at the NIH, the University of Arizona, and two institutes in Quebec, Canada.

The researchers previously found that activating the A3 adenosine receptor (A3AR) pathway provides significant pain reduction. Their current studies aimed at discovering the mechanism by which A3AR provides pain relief. They found that the A3AR drugs activated gamma amino-butyric acid (GABA). This inhibitory transmitter system turns off the signals that cause the pain sensation in the brain and spinal cord. In patients with chronic pain, GABA signaling is reduced or lost.

A3AR drugs are already in clinical trials as anti-inflammatory and anti-cancer treatments with good results, which could mean that this treatment may be on its way to helping patients suffering from chronic pain.

For more information, read the full article in Newslink.

DNA2 and Replication Fork Reversal
April 15, 2015

Alessandro Vindigni, Ph.D., recently published a paper in the Journal of Cell Biology detailing the Vindigni Lab’s work on the role of DNA2 in reversed replication fork processing and restart. The article was selected as a Faculty of 1000 publication for its significance in the field. This group of over 5000 expert scientists and researchers review and highlight top biomedical research.

DNA lesions occur frequently as a result of environmental exposures. If the lesions are not repaired correctly, they can lead to mutations, cell death, or cancer. Fork reversal allows the cell to repair these lesions using reversed forks. These results are not only important for showing how cells prevent mutations or cancers from forming, but could also show possible therapies for blocking cancer cells from replicating by preventing the fork reversal process from working. Control of DNA replication forks is highly important to maintaining genome integrity, and these studies identify a new mechanism in the maintenance of this system.

The lab also published an article in the same Journal of Cell Biology issue detailing their related work on the role of Rad51, a central homologous recombination factor, in fork reversal. The journal highlighted both of these articles in an In Focus discussion.

You can read the full story in Newslink.

Access the recommendation on F1000Prime

T-Cell “Policement” Help Regulate Immune System
March 31, 2015

Daniel Hawiger, M.D., Ph.D., Assistant Professor of Molecular Microbiology and Immunology, recently published an article in Immunity. Dr. Hawiger reported his research on self-reactive T-cells and their ability to “police” the overactive immune responses of other T-cells.

Some T-cells develop self-reactive properties during the T-cell education process. These cells, if left unchecked, can cause autoimmune disorders such as multiple sclerosis, and are usually deleted. However, the researchers discovered that CD5, a molecule that preserves these autoreactive T-cells from being destroyed, can retrain the cells to be regulatory T-cells that are able to help control overactive immune responses, turning potentially harmful cells into beneficial cells and minimizing the potential for autoimmune responses in the process.

For more information, read the full article in Newslink.