BioNexus KC has awarded three $50,000 grants to area scientists to support research focused on pediatric genetic diseases.
MU scientists discover possible biological markers for identifying opioid use disorder
Scientists at the University of Missouri have discovered possible biological markers that they hope could one day help identify the presence of an opioid use disorder during human pregnancy.
Cheryl S. Rosenfeld, an author on the study, said women often take opioids for pain regulation during pregnancy, including oxycodone, so it’s important to understand the effects of these drugs on the fetal placenta, a temporary organ that is essential in providing nutrients from a mother to her unborn child. Rosenfeld is a professor of biomedical sciences in the College of Veterinary Medicine, investigator in the Christopher S. Bond Life Sciences Center and research faculty member in the Thompson Center for Autism and Neurodevelopmental Disorders.
According to the Centers for Disease Control and Prevention, the number of pregnant women diagnosed with an opioid use disorder has quadrupled between 1999 and 2014.
“Many pregnant women are being prescribed opioids — in particular OxyContin, or oxycodone — to help with the pain they can experience during pregnancy, and this can lead to opioid use disorders,” Rosenfeld said. “Many women also don’t want to admit to taking these drugs, and we know that children born from mothers who have taken opioids during pregnancy experience post-birth conditions, such as low-birth weight. But, so far no one has studied the potential ramifications of opioid use during fetal life. Thus, we focused on the placenta because it is the main communication organ between the mother and her unborn child.”
Previous studies examining these effects have used human cell cultures, but this is one of the first studies to use an animal model to examine how developmental exposure to these drugs affect the conceptus. In the study, Rosenfeld and her colleagues focused on how a mother’s use of oxycodone during her pregnancy can affect a mouse’s placenta. Mouse and human placentas are similar in many ways, including having placenta-specific cells in direct contact with a mother’s blood. They found the use of this drug during pregnancy can negatively affect the placenta’s structure, such as reducing and killing cells that produce by-products needed for normal brain development. In addition, Rosenfeld said their findings show specific differences in genetic expressions between female and male placentas in response to maternal oxycodone exposure.
“Our results show when mothers take oxycodone during pregnancy, it causes severe placental disruptions, including elevation of certain gene expressions,” Rosenfeld said. “We know what the normal levels should be and if there are any changes, then we know something might have triggered such effects. For instance, in response to material oxycodone exposure, female placentas start increasing production of key genes essential in regulating material physiology. However, in male placentas, we see some of these same genes are reduced in expression. These expression patterns could be potential biomarkers for detecting exposure to oxycodone use.”
Rosenfeld said by studying this in an animal model, it allows scientists to see these changes quicker than if they were completing a comparable study in people, because a pregnant mouse can give birth in 21 days compared to about nine months in people.
“This also allows us to easily study other regions of the body, especially the brain of exposed offspring, that would be affected by taking these opioids,” Rosenfeld said. “We can then use this information to help epidemiologists identify behaviors that people should be looking at in children whose mothers have taken these opioids.”
Rosenfeld suggests that opioids should be added to other widely discussed warning factors during pregnancy, such as smoking and drinking alcohol. She said short-term use of opioids by pregnant women, such as someone who has kidney stones, might not cause much of an effect on their pregnancy, but that likely depends on when the mother is taking the drug while pregnant. Future plans for this study include analyzing how offspring are affected once they are born.
Rosenfeld’s research is an example of an early step in translational medicine, or research that aims to improve human health by determining the relevance of animal science discoveries to people. This research can provide the foundation for precision medicine, or personalized human health care. Precision medicine will be a key component of the NextGen Precision Health Initiative — the University of Missouri System’s top priority — by helping to accelerate medical breakthroughs for both patients in Missouri and beyond.
The study, “Maternal oxycodone treatment causes pathophysiological changes in the mouse placenta,” was published in Placenta, the official journal of the International Federation of Placenta Associations. Other authors include Madison T. Green, Rachel E. Martin, Jessica A. Kinkade, Robert R. Schmidt, Nathan J. Bivens and Jiude Mao at MU; and Geetu Tuteja at Iowa State University.
Funding was provided by grants from the National Institute of Environmental Health Sciences and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
MU researchers identify novel RNAs that could serve as biomarkers for early disease detection.
Pancreatic cancer is rarely detected at its early stages because symptoms often do not present themselves until after the cancer has progressed. By then, invasive procedures such as surgery, chemotherapy or radiation are often needed to treat the cancer.
Now, researchers at the University of Missouri’s College of Veterinary Medicine and School of Medicine have identified novel pieces of biological information, such as RNA, which may serve as biomarkers for early detection of pancreatic cancer.
“If we can identify the potential for disease development as early as possible, preventative measures can be taken by the patient, which will ultimately lead to improved health outcomes,” said Senthil Kumar, a research professor in the MU College of Veterinary Medicine. “By drawing a blood sample in a minimally invasive manner, we can analyze the nano-carriers called ‘exosomes’ that are present in the bloodstream, which contain different biological information from normal and tumor cells.”
In this initial collaborative study between Kumar and surgeons Eric Kimchi and Jussuf Kaifi from MU Health Care’s Ellis Fischel Cancer Center, the researchers analyzed the blood samples of healthy individuals and patients at different stages of pancreatic disease. They identified novel RNAs that can be useful in distinguishing between healthy and cancerous conditions in the pancreas.
Screening both cancerous and non-cancerous subjects allows researchers to compare biological patterns to see if certain populations, such as those with a family history of pancreatic cancer, might be more predisposed to develop the disease.
“Identifying these biomarkers early on can help us learn of one’s susceptibility for disease development,” Kumar said. “Our goal eventually is to keep people well-informed so they have a greater awareness regarding any preventative measures.”
While these studies are in the initial phase, more patient studies, which are currently ongoing, will shed light on the potential of identified biomarker applications in pancreatic disease.
This interdisciplinary collaboration between the MU College of Veterinary Medicine and MU School of Medicine helps advance precision medicine, one of the core principles of the NextGen Precision Health Initiative. Identifying specific biomarkers in various populations will ultimately lead to more individualized treatment plans and improved health outcomes.
“RNA cargos in extracellular vesicles derived from blood serum in pancreas associated conditions” was recently published in the February 2020 edition of the journal Scientific Reports.
Story courtesy of Mizzou News Bureau
Contact: Brian Consiglio, 573-882-9144, firstname.lastname@example.org
The Laboratory for Infectious Disease Research (LIDR) at the University of Missouri is a regional biocontainment laboratory located on the Columbia campus. The LIDR is critical for collaborating scientists who perform research on infectious diseases and is part of our nation’s effort to protect public health. In recent months, COVID-19 has become an important topic of research for the scientists who work in the LIDR.
Jeffrey Adamovicz, PhD, is the LIDR’s director. He is responsible for the safe operation of the facility and providing support for users, ensuring they can complete their intended research.
“The LIDR facilitates regional research on what we call ‘high-consequence pathogens’,” says Adamovicz. “These high-consequence pathogens can be toxins, viruses, bacteria or fungi.”
As part of that effort, LIDR researchers procured a sample of the virus that causes COVID-19.
“We foresaw the need to conduct research on campus to help understand the basic virus biology and help work toward the creation of therapeutic treatments, diagnostics, medical devices and vaccines,” Adamovicz says.
Guidelines for the safe handling and research of SARS-CoV-2 were published by the Center for Disease Control and Prevention. They state that work beyond routine specimen testing should be conducted only under biosafety level 3 (BSL3) conditions and practices. The LIDR is the only facility on the MU campus that operates under BSL3. Researchers conduct studies for model development, vaccine creation and analysis, therapeutics testing, vector-borne disease prevention, host-pathogen interaction and host immune response. The LIDR also houses specialists in aerobiology and immunology who facilitate and support research, which furthers the capacity for research on COVID-19.
Professor of Veterinary Pathobiology and Associate Dean for Research Christian Lorson, PhD, detailed the importance of this kind of facility. “This is very important work that can really only be accomplished in a handful of locations across the country and to have this facility within the CVM presents an outstanding opportunity to help animals and humans,” said Lorson. “Perhaps now more than ever it has become increasingly clear that having a strong infectious disease program is critical for a research institution like MU, as the LIDR was able to quickly pivot and is now able to assist in the multi-pronged research effort to understand and stop the COVID-19 pandemic.”
The LIDR currently has a multitude of collaborations in discussion for product efficacy testing, model development, and vaccine and therapeutics research. Associate Director for the LIDR and Assistant Research Professor in Veterinary Pathobiology Paul Anderson, PhD, explained this process. “We have been contacted by dozens of investigators who want to collaborate with us to test everything from antiviral therapeutics, vaccinations, host-immunomodulating compounds and different products that claim to have antiviral properties,” said Anderson. “All these things need to be verified so we’ve been spending a lot of time over the last couple of months working with people to submit grant applications and other nondisclosure agreements to try to get all this moving.”
According to Adamovicz, the overarching goal of the LIDR’s COVID-19 research and testing is to generate knowledge that will help alleviate the current pandemic, as well as provide a better foundation of knowledge for future coronavirus outbreaks. While knowledge is the main goal, Adamovicz says the LIDR’s research may be able to provide a solution. “It is likely that we may deliver new drugs or a novel vaccine candidate for the disease,” says Adamovicz. “The University of Missouri has talented faculty that are up to the challenge and can work alongside the best researchers in the country. When Mizzou agreed with the National Institutes of Allergy and Infectious Disease to host the LIDR over 10 years ago, it was with the possibility of a pandemic disease in mind. So, hats off to that foresight and kudos to MU to have a facility of this type to help serve the citizens of Missouri.”
By Nick Childress
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