Research News

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. The trial is set to begin in a few months.

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.

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.

Research Reveals New Drug to Treat NASH Liver Damage
February 18, 2015

Thomas Burris, Ph.D., Professor and Chair of Pharmacological and Physiological Science, recently published an article in Molecular Metabolism. Dr. Burris and a team of researchers, including Colin Flaveny, Ph.D., Kristine Griffett, Ph.D., Grant Kolar, Ph.D., Brent A. Neuschwander-Tetri, M.D., and Ryan Welch, reported their findings on a possible new drug to prevent nonalcoholic steatohepatitis (NASH), a form of fatty liver disease caused by accumulation of fat in the liver.

The researchers developed a liver-specific drug, SR9238, that targets a receptor in the liver that regulates fat synthesis and transport. Mice on a special diet that mimics the high trans-fat and high fructose diet consumed by patients with NASH were treated with SR9238, which stopped the scarring and damage that ofter occurs during disease progression. Though clinical trials will need to be done, these early results are promising for a disease that currently has no approved treatment.

For more information, read the full article in Newslink.

Opioids and Depression
February 9, 2015

Jeffrey Scherrer, Ph.D., Associate Professor of Community and Family Medicine, recently published an article entitled “Change in opioid dose and change in depression in a longitudinal primary care patient cohort” in the February 2015 issue of Pain (156(2):348-355). Dr. Scherrer found that patients taking high doses of opioid medicines to manage pain had an increased incidence of depression.

The researchers used questionnaires from patients in nine different practices to assess pain level, duration of pain, and dose of opioid medication to determine how these factors affect on-going and new-onset depression. They found a strong correlation between length of use of opioid medication and increased risk of depression. The team is now analyzing medical records from the Veterans Administration to continue their research.

For more information, read the full article in Newslink.

Promising New Therapy for Type II Diabetes
January 30, 2015

Andrew Butler, Ph.D., Professor of Pharmacological and Physiological Science, recently published an article in Molecular Metabolism. The article details his research on adropin, the hormone that regulates whether fat or sugar is burned during feeding or fasting cycles.

The researchers found that treatment of obese, diabetic mice with adropin improved glucose utilization and enhanced insulin action, alleviating the effects of glucose intolerance and diabetic symptoms. These results could lead to promising new treatments for diabetic patients to control blood sugar, or even to prevent the development of diabetes in glucose-intolerant patients.

Dr. Butler’s group previously reported on adropin and its role in feeding and fasting several years ago and recently published a paper in Diabetes reporting how adropin helps regulate what fuel muscle cells utilize during fasting and feeding cycles.

For more information, read the full article in Newslink.

Improved Antibiotics for Staph Infections
January 27, 2015

Francis Yap, Ph.D., Assistant Professor of Biochemistry and Molecular Biology, recently published an article in the Proceedings of the National Academy of Science. The article reports her findings on how bacteria become resistant to antibiotics, perhaps giving researchers a way to circumvent this mechanism.

The researchers studied a process in bacterial ribosomes called “ribosome stalling,” which allows the bacteria to delay genetic material copying, allowing the bacteria to survive in the presence of antibiotics and giving it time to activate translation of the resistance gene. The team hopes to show that this process is universal among bacteria and that it will help improve the effectiveness of antibiotics currently in use.

For more information, read the full article in Newslink.

Preventing Type I Diabetes in Mice
January 24, 2015

Thomas Burris, Ph.D., Chair of Pharmacological and Physiological Science, recently published an article in Endocrinology detailing his group’s studies on whether blocking the autoimmune process that destroys pancreatic beta cells, which produce insulin, would prevent mice from developing Type I diabetes.

The researchers found that mice treated with SR1001, a selective agonist developed by Dr. Burris, did not develop diabetes, even when the treatment was started after significant beta cell damage had occurred. Their treatment could slow or even eliminate diabetic symptoms in patients with Type I diabetes or help significantly reduce their dependence on insulin.

For more information, read the full article in Newslink.