Blog

Advocacy by the research community – a renewed beginning

Guest Blog By: Peter Vitiello, PhD - Assistant Scientist, Environmental Influences on Health and Disease Group, Sanford Research

Science advocates across 65 countries will participate in over 600 coordinated marches to highlight the influence of research on our society and promote a call of support for the research community. Some skeptics think these organized events can paint scientists as a partisan special interest group in polarized political climates. Regardless of your opinion on the value of these marches, it is undeniable that many scientists have a renewed desire to voice their opinion by building long-standing relationships with their local communities and representatives in government.

There are several easy ways to communicate with your local representatives. Social media outlets such as Twitter can quickly engage groups of individuals and comments are monitored by staffers. However, the impact of social media activism can depend on your number of followers. Although email may be a preferred method, writing a letter to your representative’s local office is often more effective because it guarantees that it will be read. The most effective thing to do is call their local office because it is the most timely approach and staffers will document and communicate your message. Just be sure to be kind and thank the staffers answering the phones since they may be fielding nonstop phone calls for eight hours every day.

While this strategy is an excellent way to register your message, it doesn’t necessarily communicate the value of your opinion as a scientist. An excellent way to articulate information about yourself and your professional opinion is to communicate with people in your community, since most of them have never met a single scientist. I was recently able to interact with several community organizations to discuss the influence of research on our society. One group was from the Osher Lifelong Learning Institute which provides learning opportunities for people over 50 years old. Another group was the Lions Club comprised of local business leaders. These networking organizations (local chambers, policy advocacy groups) can also serve as a gateway to local representatives. I found these dynamic forums to be an excellent way to overcome and important stigmatic barrier, allowing community members to interact with local scientists.

As researchers, we are constantly inundated with communicating our ideas and findings to the rest of the scientific community but often neglect ways to interact with people and leaders in our own backyards. The best way to be heard is to take ownership of being a community leader, a responsibility that should be embraced by every scientist.

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Meet a Real Woman in Science: Yvonne Janssen-Heininger

Dr. Yvonne Janssen-Heininger of the University of Vermont’s Dept. of Pathology and Laboratory Medicine grew up in the Netherlands and first discovered her love of lung research as an undergraduate, when she looked at different organ tissues under a microscope.   Yvonne and her team currently investigate the role of redox biology and fibrosis in the lungs to elucidate pathology mechanisms and to develop novel drugs to treat chronic lung disease. 

Dr. Janssen-Heininger is a leading author in scientific publications and her discoveries are highly cited by her peers (Hirsch index h = 46, Scopus). She is a world-leading expert on protein-thiol redox signaling, the biology of epithelial cells and pulmonary fibrosis. Since 2010, Yvonne has served as a member and elected Chair of the Lung Injury Repair and Remodeling Study Section of the National Institutes of Health. She has been a member of SfRBM since 1997 and served on the leadership Council as Secretary-Treasurer.

Although Yvonne loves science and enjoys reading articles on lung injury, she also enjoys reading Nicholas Sparks novels; it’s on her recommended reading list!  Yvonne also enjoys cooking and calls herself a “hit and mostly miss cook” because she is forever trying new recipes, which range from absolutely delicious to maybe not so great.

SfRBM’s Women in Science Committee is proud to recognize Yvonne Janssen-Heininger and her research. To learn more about Yvonne and other amazing female scientists like Daret St. Clair and Samantha Giordano, check out the SfRBM “Featured Women in Science” page here (http://sfrbm.org/resources/women-in-science/).

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Category: SfRBM Member Profile


New Study on Mice May Hold Keys to Disease Therapies

Scientists at Sanford Research have just developed a new model that could have lasting implications for some of the world’s most dangerous diseases like cancer, diabetes, neurodegeneration, heart disease, and respiratory distress syndrome.

The new study, led by Peter Vitiello, PhD, Associate Scientist, Children's Health Research Center at Sanford Research, was recently published in Free Radical Biology and Medicine, a journal of the Society for Redox Biology and Medicine (SfRBM).

Many tissue processes and disease pathologies in the human body are influenced by disturbances in cellular redox, an imbalance in the generation and detoxification of chemical oxidants. Thioredoxin-1 (Trx1) is an antioxidant enzyme synthesized by every human cell to detoxify proteins damaged by chemical oxidants. Understanding fundamental molecular functions of Trx1 may provide new therapeutic strategies to prevent disease progression during cellular redox imbalance.

To understand how Trx1 functions during redox alterations and disease pathogenesis, the study described a novel mouse genetically engineered to identify proteins detoxified by Trx1 in lung.

“As we better understand how molecules sense and regulate cellular responses to redox imbalances at the core of so many human disease, we can then improve therapies and treatments that will save lives,” said Dr. Peter Vitiello an Associate Scientist at Sanford Research and SFRBM member.  “By creating this transgenic mouse designed to identify proteins targeted by thioredoxin-1, we can learn new information about molecular responses in cells during redox perturbations which we hope will lead to new therapeutic approaches that hinder progression of diseases such as respiratory distress syndrome and neurodegeneration.”

Specifically, Dr. Vitiello’s research team engineered a mutation in the thioredoxin-1 mouse gene that stabilizes interactions with proteins targeted for detoxification by thioredoxin-1. The mutant thioredoxin-1 is then purified along with any bound proteins which are subsequently identified by mass spectrometry.  To demonstrate how this technology can be applied to understand disease processes, transgenic mice were treated with excess oxygen to cause lung injury, and Dr. Vitiello found that there were unique sets proteins bound to thioredoxin-1 which were exclusively detected in either control of treatment groups.

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Redox Biomarker Could Predict Progression of Epilepsy

Approximately 2.9 million people in the United States suffer from epilepsy, according to the CDC. For patients living with this diagnosis and their doctors it is often difficult to predict the onset or progression of chronic seizures. Thanks to a newly published study from the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences at the Anschutz Medical Campus, that may be changing.

The study, led by Drs. Manisha Patel and Li-Ping Liang of the University of Colorado, was recently published in Redox Biology, a journal of the Society for Redox Biology and Medicine (SFRBM).

The study was designed to determine if the ratio of reduced and oxidized forms of an amino acid, cysteine and cystine respectively, could serve as an accurate biomarker to predict the onset or progression of seizures associated with epilepsy. Using a rat model, it was determined that decreased cysteine/cystine ratio in plasma may serve as a redox biomarker in epilepsy.

Specifically, seizures were chemically-induced in rats, which were then monitored closely for behavioral changes. Plasma was then taken from the rats 48 hours and 12 weeks after treatment to mimic acute and chronic epileptic conditions. It was found that cysteine/cystine ratio was an accurate redox biomarker for epilepsy. Plasma cysteine/cystine was reduced over 60% in rats with acute epileptic responses and over 37% in rats with chronic epilepsy. Interestingly, cysteine/cystine ratio was unaltered in rats also treated with an antioxidant known to prevent epileptic brain injury.

“Currently the field of epilepsy lacks peripheral blood-based biomarkers that could predict the onset or progression of chronic seizures following an epileptogenic injury,” said Dr. Manisha Patel a Professor at the University of Colorado School of Pharmacy and SFRBM Member. “We are confident that this study is a significant step toward changing this, and will one day help those living with temporal lobe epilepsy.”

About Dr. Patel’s lab

The overarching theme of research in Dr. Patel’s laboratory is to understand the role of redox and metabolic mechanisms in epilepsy. Her laboratory has provided compelling evidence for the role of reactive species and mitochondrial dysfunction in animal models of epilepsy. Furthermore, her research has identified reactive species as novel targets for co-morbidities of epilepsy.

About the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

Since its inception in 1911, the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences has experienced numerous milestones and is ranked in the top 20 percent of all schools of pharmacy in the country, and fourth in the nation for total NIH funding. Committed to pharmaceutical education, research and patient care, the School educates students in the properties of medicinal agents, the biology of disease, the actions of drugs, and best practices for clinical and therapeutic uses of drugs. Located at the Anschutz Medical Campus, the University of Colorado is the only completely new education, research and patient care facility in the nation today.

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Categories: Free Radical Biology and Medicine, Redox Biology, Research


Simultaneous quantitation of oxidized and reduced glutathione via LC-MS/MS: An insight into the redox state of hematopoietic stem cells

Click here to read the full study in the journal: Free Radical Biology and Medicine

Cellular redox balance plays a significant role in the regulation of hematopoietic stem-progenitor cell (HSC/MPP) self-renewal and differentiation. Unregulated changes in cellular redox homeostasis are associated with the onset of most hematological disorders. However, accurate measurement of the redox state in stem cells is difficult because of the scarcity of HSC/MPPs. Glutathione (GSH) constitutes the most abundant pool of cellular antioxidants. Thus, GSH metabolism may play a critical role in hematological disease onset and progression.

A major limitation to studying GSH metabolism in HSC/MPPs has been the inability to measure quantitatively GSH concentrations in small numbers of HSC/MPPs. Current methods used to measure GSH levels not only rely on large numbers of cells, but also rely on the chemical/structural modification or enzymatic recycling of GSH and therefore are likely to measure only total glutathione content accurately.

Here, we describe the validation of a sensitive method used for the direct and simultaneous quantitation of both oxidized and reduced GSH vialiquid chromatography followed by tandem mass spectrometry (LC-MS/MS) in HSC/MPPs isolated from bone marrow. The lower limit of quantitation (LLOQ) was determined to be 5.0 ng/mL for GSH and 1.0 ng/mL for GSSG with lower limits of detection at 0.5 ng/mL for both glutathione species. Standard addition analysis utilizing mouse bone marrow shows that this method is both sensitive and accurate with reproducible analyte recovery.

This method combines a simple extraction with a platform for the high-throughput analysis, allows for efficient determination of GSH/GSSG concentrations within the HSC/MPP populations in mouse, chemotherapeutic treatment conditions within cell culture, and human normal/leukemia patient samples. The data implicate the importance of the modulation of GSH/GSSG redox couple in stem cells related diseases.

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Categories: Free Radical Biology and Medicine, Redox Biology, Research