Research Bulletin
News from the Child Health Research Institute
July 2021
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NIH Selects CHRI Study Led by Dr. Rusty McCulloh for Major COVID-19 Initiative |
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The National Institutes of Health has funded a CHRI study as part of an initiative to discover best methods of deploying coronavirus diagnostics to children of vulnerable and underserved populations and to support their safe return to school during the COVID-19 pandemic. The UNMC study, titled “Mobile Health-Targeted SARS-CoV-2 Testing and Community Interventions to Maximize Migrant Children's School Attendance During the COVID-19 Pandemic,” was one of just five selected in the U.S.
Rusty McCulloh, MD, UNMC associate professor and chief of the Division of Pediatric Hospital Medicine for UNMC and Children’s, serves as the primary investigator of the study. Chad Abresch, PhD, assistant professor, Division of Child Health Policy, UNMC, and Ellen Kerns, assistant professor, Division of Child Health Policy, UNMC and Children's data scientist, also collaborated on the study. Michelle Warren, PhD, associate professor of Spanish at University of Nebraska at Kearney, facilitated the connection between the UNMC team and the central Nebraska migrant programs whose families will be served through this project.
The study is part of the second installment of the Safe Return to School Diagnostic Testing Initiative, which is a feature of the NIH Rapid Acceleration of Diagnostics Underserved Populations (RADx-UP) program. These awards will deliver up to $15 million over two years for projects based in Nebraska, Arizona, California, Florida and Hawaii.
The stated goal of the CHRI study is to “address critical gaps in public health mitigation and social responses faced by migrant children and their families living in rural Nebraska.” At-home SARS-CoV-2 saliva tests will be employed to identify instances of infection in the households of migrant families with school-aged children who participate in the Nebraska Migrant Education Program. The study will use mobile and wireless technologies to identify candidates for testing and to provide links for public aid and community assistance to address adverse social impacts associated with COVID-19.
The CHRI study, along with other projects funded under the RADx-UP umbrella, seek to address the gap in access to COVID testing among some underserved populations. They are also designed to speed along in the process of returning to school children who often face barriers to attending school remotely. Returning to school allows children to receive benefits such as school-based meals, therapy treatments and after school programs. According to the NIH, minorities, socially and economically disadvantaged children and children with disabilities and medical complexities are disproportionately affected by the loss of the benefits of attending school in-person.
Dr. McCulloh explains, " Migrant children and families in Nebraska are particularly vulnerable to the negative impacts of the COVID-19 pandemic. Our project builds on successful work performed at Children's and UNMC to identify and address the direct harms of the pandemic due to infection, as well as from the indirect negative effects on families' health and well-being. Given that over 200,000 children participate in the migrant education program nationally, our team’s hope is that our project will provide a template for other migrant education programs to use for maximizing students' school attendance and family resiliency in the face of a widespread disaster."
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CHRI Priorities & Activities:
Update from Ann Anderson Berry, MD
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This month, Ann L. Anderson Berry, MD, PhD, interim executive director, Child Health Research Institute (CHRI) looks back on the past month.
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UNMC Core Facility Profile:
The Flow Cytometry Research Facility
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Craig L. Semerad, PhD, Director of the Flow Cytometry Research Facility (FCRF) graciously answered our questions about FCRF’s utility for CHRI members’ research efforts.
What kind of services can you provide CHRI investigators?
The Flow Cytometry Research Facility (FCRF) is a fee-for-services shared resource laboratory providing comprehensive research flow Cytometry services, education and training to all investigators on the UNMC campus, as well as other regional academic and corporate partners. The FCRF provides support in all areas of established protocols and development of new applications guided by investigator needs. Routine analyses include immunophenotyping, DNA and cell cycle determinations, fluorescent protein expression, bead-based assays for secreted proteins and high-speed cell sorting (bulk and single-cell sorting) using state-of-the-art instrumentation. Given the complexity, high-costs and specialized knowledge needed to operate flow cytometry instrumentation, the FCRF acts as an essential research partner to investigators in the experimental design, sample preparation, acquisition, analysis and presentation of flow cytometry data.
If an investigator wants to learn more about utilizing the services of the Flow Cytometry Research Facility, what is a good way of getting needed information?
Investigators interested in learning more about the FCRF may visit our website.
In addition, feel free to contact FCRF personnel with any questions about available services and procedures via phone or email:
Victoria Smith, B.S., FCRF Coordinator
402-559-6267
Holly Britton, M.S., FCRF Technician
402-559-6267
Craig Semerad, Ph.D., SCYM(ASCP)CM, FCRF Director
402-559-6299
What are the first steps towards engaging the services of the Flow Cytometry Research Facility?
To continue reading the Flow Cytometry Research Facility profile click here.
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Dr. Ann Anderson Berry Leads Grant Awarded through
the University of Nebraska Collaborative Initiative
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Anderson Berry, MD, PhD, division chief of Neonatology at Children’s and a professor, Department of Pediatrics at UNMC, is the principal investigator of a new grant through the University of Nebraska Collaboration Initiative. Titled “Omega 3 - fatty acid: Potential for mitigation of neurodevelopmental outcomes from in utero opioid exposure in a chronic stress rat model,” the one-year project was funded in the amount of $40,000, starting
July 1.
The stated purpose of the Collaboration Initiative is “to enhance competitiveness of University of Nebraska faculty for extramural funding by fully leveraging intellectual capacity and research resources across the campuses.” The award to Dr. Anderson Berry’s team is a Preliminary Data and Application Preparation Grant, which is designed to promote research collaborations between faculty members at University of Nebraska campuses who are developing innovative research that fits the objectives of an extramural funding agency. Dr. Anderson Berry answered some questions about the project.
Who are your fellow investigators in this multi-campus project?
My co-investigators for this project are Gurudutt Pendyala, PhD, associate professor
research faculty, UNMC Department of Anesthesiology; Corrine Hanson, PhD, associate professor/associate program director, Medical Nutrition Education, UNMC College of Allied Health Professions; Ashley Blount, PhD, assistant Professor in the Department of Counseling in the UNO College of Education; and Dr. Charmayne Adams, PhD, assistant professor in the Department of Counseling in the UNO College of Education. We are excited to bring together UNMC and UNO. The team's three overlapping research areas of expertise allow us to better understand a complicated real-world situation with an eloquent animal model study.
What ideas about treating in utero opioid exposure are you seeking to explore through this research?
This project is based on a series of preliminary data that shows the following:
- In utero opioid exposure in a rat model leads to decreased brain growth and altered neuronal migration patterns in exposed rat pups.
- Opioid use in maternal populations is often associated with chronic social stressors, and chronic stress supports a proinflammatory intrauterine environment that can be associated with poor growth of the fetus.
- Micronutrients, including omega 3 - fatty acids, can have a positive impact on inflammation through a series of metabolites called pro-resolving mediators, and levels of intake can mitigate in utero inflammatory risk.
We are interested in evaluating the possibility of augmentation or reduction of brain development changes seen in utero in Dr. Pendyala's opioid exposed rat pup model by administering and withholding maternal omega - 3 fatty acids that are linked to mitigation of inflammation, with the addition of chronic stress to his standard opioid exposure model.
What are the advantages of the chronic stress rat model in helping your team explore these problems and interventions?
The chronic stress rat model allows our research team to more closely mimic the intrauterine environment of the exposed neonate whose mother has an untreated substance use disorder. This work is novel and can lead to feasible and low-cost interventions in pregnancy if our hypothesis is proven correct.
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Dr. Sathish Kumar Natarajan Leads Group of
Researchers Studying Zika Transference from Mother to Fetus
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In recent years, there was extensive media attention to Zika virus, particularly its ability to cause severe disease manifestations like microcephaly when transmitted from an infected pregnant woman to her fetus. Sathish Kumar Natarajan, PhD, UNL assistant professor in the Department of Nutrition and Health Sciences, leads a group of researchers at both UNL and UNMC who have been studying how Zika virus breaches the placental barrier, and how transmission can potentially be blocked. He kindly took time to respond to questions for the Research Bulletin.
What kinds of damage and stress does Zika virus cause when it infects the placental tissue?
Zika virus (ZIKV) infection to placental trophoblasts causes endoplasmic reticulum (ER) stress, activation of cJun N-terminal kinase (JNK) and causes caspase-dependent trophoblast apoptosis as evidenced by significant increase in percent apoptotic nuclei and caspase 3/7 activation following ZIKV infection. Further, we have shown that inhibition of JNK using small molecule inhibitor prevents ZIKV-induced trophoblast apoptosis.
What led you to investigate palmitoleate as a compound that might interfere with infection of placental cells, and how did your team test its effects?
Palmitoleate is an omega-7 monounsaturated fatty acid. Our previous work has shown that palmitoleate protects against saturated free fatty acid-induced trophoblast lipoapoptosis. We used an in vitro cell culture system using placental trophoblasts to demonstrate the protective role of palmitoleate against ZIKV infection-induced ER stress and apoptosis. I would also like to thank my awesome team members for their critical inputs and support.
Which of the findings in this study is/are most valuable in understanding the Zika virus transmission mechanisms?
Palmitoleate significantly reduces ZIKV infection-induced trophoblast apoptosis and interferes with ZIKV replication in trophoblasts. Further, palmitoleate treatment after ZIKV infection in trophoblasts downregulates the activation of ER stress markers that occur due to viral protein overload; however, palmitate, a saturated fatty acid with similar carbon structure to palmitoleate, augments cell death in ZIKV-infected trophoblasts.
Where is this research taking you next?
Our future goal is to study further mechanistic studies in elucidating the protective role of palmitoleate and to test its protective role using an in vivo animal model of the Zika virus infection using STAT2 knock in mice.
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Meet a fellow CHRI Member |
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Kishor Bhakat, PhD, RN, CCRN-K, is an associate professor in the Department of Genetics and Cell Biology and member of the Fred and Pamela Buffet Cancer Center.
What is your current primary area of research?
My research is primarily focused on DNA damage repair and transcriptional regulation in tumor cells. One of our research interests is to elucidate the mechanisms by which Medulloblastoma (MB), a pediatric brain cancer, cells become resistant to chemotherapy.
Please share information on a current research project.
Medulloblastoma (MB) is a highly aggressive pediatric brain tumor. Post-surgical radiotherapy, in combination with cisplatin-based chemotherapy, are used to inhibit the growth of highly chemoresistant tumor cells.
Unfortunately, administration of a platinum-based chemotherapy is complicated by prominent dose-limiting neurotoxicity, which affects the quality of life of childhood cancer survivors. Our overall goal of research is to identify novel therapeutic targets to increase efficacy of cisplatin in patients with MB. Our research demonstrates a new role of DNA repair protein APE1 and the nucleosome remodeling FACT complex in promoting chemo-radiation resistance in MB. It further shows that targeting these factors with small molecules can be used to improve the efficacy of interventions for MB and outcomes in high-risk patients.
What has been the primary benefit of CHRI membership?
CHRI membership has provided opportunity for developing new collaborations. This has also been helpful in supporting our research through intramural grant funding.
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Siddappa Byrareddy, PhD, is professor and vice-chair of Research in Pharmacology & Experimental Neurosciences; professor (Courtesy) in Department of Genetics, Cell Biology and Anatomy; Biochemistry & Molecular Biology. He is a member of the Center for Heart and Vascular Research and a member of The Fred and Pamela Buffett Cancer Center.
What is your current primary area of research?
Our laboratory’s research focuses on understanding host-virus dynamics using molecular biology, virology, immunology, systems biology and genomic tools to understand and develop therapeutics for emerging infectious diseases, focusing on HIV, Zika and SARS-CoV-2 viruses. We are utilizing non-human primates, mice, rabbit and hamster models for our in vivo studies. We have a particular emphasis on understanding HIV/SIV CNS reservoirs (includes T cells, myeloid cells) /neuroimmunology, drugs of abuse, macrophage tropism and immunotherapy for neurodegenerative diseases.
Please share information on a current research project.
Our research efforts are currently focused on developing therapeutics of both virus and host molecules for SARS-CoV-2. In addition, we have presently developed small molecule inhibitors and screened repurposed drugs to be effective in cell culture models. Furthermore, we are interested in understanding antibody-dependent enhancement (ADE) of viruses, particularly in children. Moreover, some efforts are underway to understand post-COVID-19 effects on the central nervous system.
What benefits would you like to receive through your CHRI membership?
It would be a great idea to set up working groups on research themes with constant interaction and collaborative efforts that will enhance research activities among members.
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Thank you, Drs. Bhakat and Byrareddy, for your time and responses. At this time, we are randomly selecting the members to be profiled, but if you would like to be featured, please email chri@unmc.edu. |
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PRO Education Committee Tip of the Month:
Research Study vs. QI?
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Is my idea a Research Study or a Quality Improvement (QI) Project?
A Research Study: Research is defined in the Federal Policy as, “any systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.”
To assist the IRB in determining whether your project is Human Subject Research, complete this form.
Quality Improvement: A QI project consists of systematic and continuous actions that lead to measurable improvement. The primary goal is to improve outcomes and manage change.
QI questions may be directed to:
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Disseminating Discoveries:
April Publications
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Take a minute to check out the wide range of research published by CHRI members in June. |
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Research in Academic Pediatrics Initiative on Diversity (RAPID)
Funder: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Friday, October 1, 2021 | $15,000 1 year | Grant Information
CHRI Pilot & Mini Grants
Individual Research Award
For more funding opportunities, please review the CHRI grant calendar available here.
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CHRI Global Health Area of Emphasis Mini Research Summit
Pediatric Academic Workshop: Grant Writing
CHRI 2021 Pediatric Cancer Research Symposium
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Child Health Research Institute
986847 Nebraska Medical Center
Omaha, NE 68198-6847
402-559-4032 or 402-955-7907
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