Research News

Hotel Influenza
June 11, 2018

Daniel Hoft, M.D., Ph.D., Director of the Division of Infectious Diseases, Allergy & Immunology and Director of the Center for Vaccine Development, announced the opening of a new Extended Stay Research Unit at SLU.

As part of the NIH-funded study to develop a universal flu vaccine, the new research unit will allow investigators to take vaccine testing to the next level. Human influenza challenge studies, where patients are vaccinated and then intentionally exposed to live flu virus, will be conducted at the site. After exposure, patients are quarantined in the unit for up to 10 days, and are monitored daily for flu infection and to see if they are shedding the virus. Patients much be clear of infection for 2 days before they will be allowed to return home.

Rooms in the former Water Tower Inn at Salus Center were converted to be used for these studies. The area is protected from other parts of the building with negative air pressure and an updated HVAC system.

For more information, read the full article in Newslink.

MS Drug Reduces Pain From Cancer Treatment
May 3, 2018

Daniela Salvemini, Ph.D., Professor of Pharmacology & Physiology and her research team published a paper in the Journal of Experimental Medicine detailing their studies on chemotherapy induced neuropathic pain (CINP) caused by a treatment used for multiple myeloma.

A chemotherapy drug, bortezomib, used to treat multiple myeloma and mantle cell lymphoma causes CINP in over 40% of patients. Using an animal model, investigators found that bortezomib increases sphingolipid production and that two metabolites of this molecule accumulate in the spinal cord. These metabolites, sphingosine 1-phosphate and dihydrosphigosine 1-phosphate, activate S1PR1 on the surface of astrocytes and cause neuorinflammation.

An oral drug used to treat multiple sclerosis (MS), finglolimod, inhibits S1PR1 without affecting the chemotherapeutic actions of bortezomib, and may even inhibit tumor growth.

For more information, read the full article in Newslink.

Pain Reduction for Cancer Patients
March 30, 2018

Daniela Salvemini, Ph.D., Professor of Pharmacology & Physiology published a paper in Pain detailing her studies on chemotherapy induced neuropathic pain (CINP) caused by a treatment used for colorectal cancer.

A common platinum-based chemotherapy drug, oxaliplatin, used to treat colorectal cancer causes CINP in over 60% of patients. Using an animal model, investigators found that the pain was caused by an increased expression of adenosine kinase in astrocytes and decreased adenosine signaling at the A3AR receptor. They used A3AR agonists to increase signaling, which blocked the pain without interfering with the efficacy of the anticancer treatment. A3AR agonists are already being evaluated in clinical trials as anticancer agents, and could be readily available for use in conjunction with oxaliplatin treatment.

For more information, read the full article in Newslink.

Cause of Premature Aging in Children
March 23, 2018

Susana Gonzalo, Ph.D., Associate Professor of Biochemistry, and her lab group published a paper in Cell Reports detailing her lab’s studies on Hutchinson-Gilford Progeria Syndrome (HGPS), which is caused by a single mutation in the LMNA gene that encodes the lamin A protein. Children with HGPS age rapidly and show changes typical to older age, such as hair loss, joint pains, and aging of skin, as well as an increased risk of atherosclerosis.

The mutated, shortened form of lamin A produced by the mutated gene is called progerin. The Gonzalo lab found that progerin accumulates in the nucleus of cells, leading to replication stress and stalling, as well as preventing protection of newly replicated DNA. They also found that degraded DNA that has leaked outside of the cell can cause inflammatory responses through an interferon pathway.

Their studies also uncovered a way to improve cell fitness, by treatment with vitamin D and other compounds that reduce replication stress and inflammatory response. They saw a marked reduction in toxicity from progerin after these treatments, which could lead to new therapies for HGPS.

For more information, read the full article in Newslink.

Crystal Structure Solved For Key Inflammation Protein
March 15, 2018

Sergey Korolev, Ph.D., Associate Professor of Biochemistry, published findings in Nature Communications revealing the crystal structure of the calcium-independent form of phospholipase A2β (iPLA2β). The structure sheds new light on the function, cellular localization, and regulation of this enzyme.

Calcium-independent iPLA2β plays a role in regulation of inflammation, calcium homeostasis, and apoptosis, as well as some neurodegenerative diseases, such as Parkinson’s disease. Discovering the crystal structure of the enzyme reveals locations of the catalytic domains and active sites, which could lead to development of therapeutic small molecules for treatment of disease-associated mutations.

Also pictured are Ian Miller (left), Research Assistant in the Korolev lab, and Konstantin Malley, Ph.D. (middle). Dr. Malley is a former graduate student in the department and is first author on the publication. He is in the M.D./Ph.D. program at SLU and is currently pursuing his M.D. degree.

For more information, read the full article in Newslink.

Opioid Cessation and Depression
February 8, 2018

Jeffrey Scherrer, Ph.D., Professor of Family & Community Medicine, published a study in the British Journal of Psychiatry Insight detailing his research on treating depression to increase patient success at opioid cessation.

The researchers found that when patients remained on antidepressants while stopping long-term opioid treatment for non-cancer pain, they experienced a decline in depression symptoms and were more likely to stop opioid use completely. The authors used medical record data from the Veteren’s Health Administration.

For more information, read the full article in Newslink.

A Link Between Sepsis and ARDS
February 1, 2018

David Ford, Ph.D., Professor of Biochemistry, and Jane McHowat, Ph.D., Professor of Pathology, published a paper linking sepsis to lung injury and death in patients with elevated levels of chlorinated lipids. Their findings were published in the Journal of Clinical Investigation Insight.

The paper shows that the presence of chlorinated lipids in patient blood samples at the time of hospital admission predicted whether ARDS, or acute repiratory distress syndrome, would develop as well as whether the lung injury would result in death within 30 days.

For more information, read the full article in Newslink.

Results from Phase 1 Zika Vaccine Trials
December 13, 2017

Sarah George, M.D., Associate Professor of Infectious Diseases, Allergy & Immunology, is Principal Investigator of the SLU trial to study three different doses of a Zika vaccine. The trial is part of a larger three-part investigation of the vaccine, which was developed by the Walter Reed Army Institute of Research.

Investigators recently published early Phase 1 results in Lancet, which show that the vaccine is well tolerated and has produced an immune response in over 90% of study volunteers.

For more information, read the full article in Newslink.

Studies on BRCA2-Deficient Cancer Cells
December 1, 2017

Alessandro Vindigni, Ph.D., Professor of Biochemistry, published studies in Nature Communications on BRCA-deficient cancer cells, including why these cells are more sensitive to chemotherapy drugs and a pathway used to rescue cells after drug removal.

Many chemotherapy drugs work by inducing DNA lesions, causing replication forks and blocking replication of the cell. BRCA proteins protect these stalled replication forks from degradation. The lack of protection in BRCA-deficient cells results in an increased sensitivity to chemotherapy drugs.

The researchers also found that even after the replication forks have stalled and been degraded, the cells can use the break-induced replication (BIR) pathway to rescue the degraded forks and avoid cell death. This alternate pathway could provide a second target to sensitize BRCA-deficient cells even more to chemotherapy drugs and to prevent cells from developing resistance to chemotherapy.

For more information, read the full article in Newslink.

New Drug Targets for FSHD
November 13, 2017

Francis Sverdrup, Ph.D., Research Fellow in Biochemistry, has identified several potential new drug therapies for the treatment of facioscapulohumeral muscualr dystrophy (FSHD). His findings were published in Skeletal Muscle.

FSHD is an inherited disease affecting mainly young adults. It is caused by mis-expression of the double homeobox 4 (DUX4) transcription factor in skeletal muscle. Sverdrup and colleagues screened known drug libraries and tested drugs on FSHD cells to identify the pathways involved in expression of the DUX4 gene, providing potential new therapies for treatment of the disease.

For more information, read the full article in Newslink.

The Role of Hibernating Ribosomes
October 18, 2017

Arnab Basu, Ph.D., and Mee-Ngan F. Yap, Ph.D., of the Department of Biochemistry, published recent findings on hibernating ribosomes in Staphylococcus aureus in a second high-profile journal. The article in Nature Communications details Dr. Basu’s studies on 100S ribosomes in two different bacterial species.

Staph bacteria constantly contain hibernating 100S ribosomes, while E. coli bacteria mainly form 100S ribosomes under stressful or nutrient poor conditions. In staph, only one protein factor, HPF, is needed to form the 100S ribosome and the complex is assembled differently than in E. coli. These findings may indicate possible targets for treatment of staph and other Gram-positive bacteria.

This work is related to the Yap Lab’s recent publication in PNAS. You can read more details in Newslink.

Waking Up Ribosomes
September 15, 2017

Arnab Basu, Ph.D., Postdoctoral Fellow, and Mee-Ngan F. Yap, Ph.D., Associate Professor, in the Department of Biochemistry, have discovered how hibernating, or 100S, ribosomes are re-activated by the cell. Their findings were published in the Proceedings of the National Academy of Science USA.

Bacteria conserve energy under stressful conditions by hibernating ribosomes. The Yap Lab discovered that in Staphylococcus aureus, a GTP hydrolase enzyme, HflX, wakes up the ribosomes so they can return to the active 70S form. This pathway was previously unknown.

For more information, read the full article in Newslink.

REV-ERB for Muscle Regeneration
June 20, 2017

Thomas Burris, Ph.D., Professor and Chair of Pharmacology and Physiology, and Colin Flaveny, Ph.D., Assistant Professor of Pharmacology and Physiology, published a paper in Molecular Metabolism detailing studies on the role of the nuclear receptor, REV-ERB, in muscle regeneration.

Dr. Burris previously published research showing that REV-ERB plays a role in lowering LDL cholesterol and also helps regulate internal clocks in mammals. This study showed that REV-ERB has differing roles in the different stages of muscle cell development, making it a key target for acceleration of muscle regeneration after traumatic injuries such as congestive heart failure, burns, cancer, and chronic obstructive pulmonary disease. Their research could lead to novel therapies for recovering patients.

For more information, read the full article in Newslink.

Relief for Cancer-Induced Bone Pain
June 9, 2017

Daniela Salvemini, Ph.D., Professor of Pharmacology and Physiology, published a paper in Pain detailing studies on treating metastatic bone pain, the most common form of pain in cancer patients.

Dr. Salvemini recently discovered molecular pathways that lead to pain and found that sphingosine 1-phosphate receptor subtype 1, or S1PR1, is key in the molecular cascade. Increases in S1PR1 lead to increased pain. The researchers found that blocking S1PR1 in an animal model of breast cancer metastatized to the femur resulted in blocking pain signals.

For more information, read the full article in Newslink.

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.