Research Bulletin
News from the Child Health Research Institute
July 2022
Dr. Paul Trippier Receives R01 Grant for
Batten Disease Research
Paul Trippier, PhD, associate professor, director for graduate studies in the UNMC Department of Pharmaceutical Sciences, and CHRI member, was recently awarded a five-year R01 grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development. Earlier this year, he was also selected as a UNMC Distinguished Scientist. Dr. Trippier kindly responded to our questions about his newly funded research for this article.

Your project addresses the lack of research on a rare inherited condition called neuronal ceroid lipofuscinosis (NCL), also known as Batten disease. What are major clinical manifestations of NCL?
 
NCLs, commonly called Batten disease, are a family of rare neurodegenerative diseases predominantly afflicting children and presenting in the first decade of life. In the U.S., approximately two to four out of every 100,000 children develop one of the forms of Batten disease. All NCL disorders share similar clinical presentation: vision impairment which progresses to blindness, seizures which increase in severity, cognitive and motor decline progressing to dementia and ultimately, premature death. CLN3 disease is the most common form of Batten disease with patients most typically presenting with symptoms of CLN3 disease between 4 and 7 years old.
 
What kinds of cellular dysfunction are understood to drive NCL progression?
 
A common hallmark, shared across all NCLs, is lysosomal dysfunction, resulting in the accumulation of storage material composed of autofluorescent ceroid lipofuscin and/or subunit c of mitochondrial ATP synthase. Mutations in one of 13 different genes lead to the subtyping of the NCLs. The CLN3 protein’s exact function is unknown, other than it contributes to cellular homeostasis and neuronal survival, at least in part, through its influence on apoptosis. As the protein’s function in healthy cells is unknown, its pathophysiological contribution is also poorly understood.
 
What is new and challenging about your group’s strategy for discovering targeted drug treatments? 
 
CLN2 and CLN5 subtypes of Batten disease can be treated with gene therapy but no treatment is currently available for CLN3 or CLN6 subtypes. Our research has identified small molecules that can reverse the accumulation of storage material in neurons grown from CLN3 patient-induced pluripotent stem cells (a highly phenotypic model) and can also rescue neurobehavioral deficits in a mouse model of CLN3 disease. This grant will allow us to optimize these compounds for greater potency and “drug-like” properties, understand exactly their mechanism of action, and determine what effect they have in a CLN6 disease mouse model.
 
Who are significant contributors and collaborators on this work?
 
Collaborators for this project are Yazen Alnouti, PhD, professor, UNMC Department of Pharmaceutical Sciences, who is an expert in pharmacokinetics and determining how our compounds travel through the body, and Rose-Mary Boustany, MD, professor of Pediatrics and Adolescent Medicine, Biochemistry and Molecular Biology, American University In Beirut, Lebanon. Dr. Boustany treats patients with CLN3 disease and is testing compounds developed in our lab at UNMC in mouse models of CLN3 and CLN6 disease.
CHRI Priorities & Activities:
Update from Executive Director Ann Anderson Berry, MD, PhD
New advances and opportunities almost always come with new requirements and regulations. At UNMC and CHRI and around the country we are preparing for the newest NIH Data Management and Sharing requirements which go into effect for grants submitted in January 2023. While it may be hard to imagine the depths of winter as we are enduring 100-degree days, in the grant writing cycle, six months will pass quickly.

Since this update represents a significant evolution in the nature of data sharing, UNMC is working to deploy a system-wide plan for implementation. The National Institutes of Health (NIH) will require data sharing for an enduring time, with greater emphasis on the institution’s responsibility to share the raw data in an accessible and meaningful format, even if the investigator is no longer at the institution.

Additionally, it will likely be necessary to include data sharing and storage costs in the NIH, Center for Disease Control and Department of Defense grant budgets. We do not have many details on all of this yet, but as UNMC’s institutional plans emerge, CHRI will be working to host educational events and provide templates for the portions of grants that will be impacted.

Matt Sandbulte, PhD, grant and scientific writer, and the CHRI scientific writing team will be developing regular communications regarding this topic, and we will highlight these in the CHRI newsletter. I urge you to reach out, as you are writing 2023 grants, for additional guidance as the year progresses. While this change is large, we will leverage CHRI and UNMC resources to support you and your research teams, to minimize any uncertainty and to ensure you are meeting necessary standards.

The summer programs are in full swing, and it is great to see Student Undergraduate Research Program and Medical Student Summer Research Program students in labs and supporting clinical and medical records research on both campuses. They are having a fantastic time already in their research endeavors. If you don’t have a student with you this summer, consider asking for one to work with you next year.

We are almost done planning the general details of the CHRI Annual Scientific Meeting, and abstract submissions will be open soon. Please mark your calendars for Nov. 3 and 4, as this will be a wonderful time to meet our National Scientific Advisory Board, present your work, meet with your identified Area of Emphasis (AOE) and hear presentations from the phenomenal CHRI scientists.

After a slight delay, we have scheduled our first DEI in Research Journal Club for Sept. 29 at noon. Please look for a Zoom invitation soon. We are excited to bring together the research community to discuss important diversity, equity and inclusion topics in research. The initial meeting will allow for the group to discuss the goals of the Journal Club. CME will be provided.

I hope you are having a wonderful summer and wish you productivity in your research!

Ann
Rebecca Slotkowski Earns
NIH F30/NRSA Fellowship
NIH F30/NRSA Fellowship
 
The F30 NIH grant mechanism funds the Ruth L. Kirschstein National Research Service Award (NRSA) fellowship for dual-degree MD/PhD training. On average, only one MD/PhD student receives the award per year, and a total of 12 UNMC scholars have been awarded a F30/NRSA Fellowship. This year, we are excited to announce that one of its recipients is Rebecca Slotkowski, a CHRI member and mentee of CHRI Executive Director, Ann Anderson Berry, MD, PhD. She was selected based on her research project, which garnered the support of the National Institute of Minority Health and Health Disparities (NIMHD). Ms. Slotkowski discussed her award and research with us.
 
What are the benefits of being awarded the F30/NRSA fellowship?
 
The F30/NRSA fellowship will provide financial support for the remainder of my research and clinical training at UNMC and give me opportunities to learn the process of applying for federal funding, an invaluable experience for a junior researcher.
 
How do the themes/aims of your research project address the mission of the NIMHD?
 
The mission of the NIMHD is to improve minority health and reduce health disparities. There are shocking disparities in pregnancy outcomes, with African American women being over three times more likely to die during or shortly after pregnancy than white women. My project will study how social health programming, provided through Girls Inc., Omaha, may reduce disparities in future pregnancy outcomes. Our study will determine whether teenagers and young adults who participated in Girls Inc. programming have healthier diets, lower stress levels or better cardiovascular health. Since cardiovascular complications are the leading cause of maternal mortality in the United States, we believe that improvements in cardiovascular health in young women prior to pregnancy may improve pregnancy outcomes for mothers and their infants.         
 
What are your longer-range professional goals after completing the MD/PhD?
 
My long-term career goal is to become a physician-scientist with a clinical practice in pediatrics and a laboratory focused on using community-based, participatory research methods to reduce health disparities in children.
Meet at Fellow CHRI Member
Dong Wang, PhD, professor, Department of Pharmaceutical Sciences
 
What is your current primary area of research?
 
My research focuses extensively on the design and development of polymeric prodrug nanomedicine for the treatment of musculoskeletal, inflammatory and autoimmune diseases. Among our contributions to the field, we are best known for the conceptualization of the “ELVIS” mechanism, which governs the passive-targeting of nanomedicine to inflammatory pathologies. We are also noted for our ground-breaking effort in the development of bone-targeted nanomedicine for skeletal, dental and periodontal diseases. Through collaboration with clinicians and biologists, we take the “reversed molecular engineering” approach to design and synthesize diverse pharmaceutical formulations, with full consideration of the pathophysiological features of each specific disease.
 
Please share information on a current research project. 
 
Currently, we are working on the development of a thermoresponsive polymeric dexamethasone prodrug (ProGel-Dex) for the treatment of osteoarthritis (OA) pain. The aqueous solution of the polymeric prodrug is a transparent and free-flowing liquid at 10˚C. It transitions into a hydrogel at body temperature. Upon a single intra-articular injection, ProGel-Dex forms a hydrogel in the joint space and provides a complete and sustained OA pain relief for four months in a destabilization of the medial meniscus (DMM) mouse model of OA.
 
What has been the primary benefit of CHRI membership?
 
For me, the primary benefit of CHRI membership is the direct contact with pediatric clinicians, whose rich clinical knowledge and experience are invaluable in guiding my translational research.
Health Services, Policy & Population Health
Mini Research Summit to Highlight Emerging Trends and Civic Tech
The CHRI Health Services, Policy & Population Health area of emphasis group is convening a mini-summit on July 19 from 12:30 to 4:30 p.m.
 
The virtual event will feature a panel discussion on population health and emerging trends, featuring:
  • Ryan Cameron, EdD, Vice President, Technology & Innovation, Children’s Hospital & Medical Center
  • LaShaune Johnson, PhD, Associate Professor, Clinical Research and Public Health, Creighton University
  • Nancy Williams, President/CEO, No More Empty Pots
 
Heath Services, Policy & Population Health area of Interest co-chair, Russell McCulloh, MD, Chief, Division of Hospital Medicine, will discuss his NIH RADxUP Safe Return to School Diagnostic Testing Initiative, and David Dzewaltowski, PhD, Endowed Community Chair & Professor, Health Promotions, UNMC, will report on his current study, Community and Child Population Health: Wellscapes Rural Community Randomized Trial - Physical Activity Effectiveness and Implementation Outcomes.
 
Bibhusha Karki, MDP, senior public health project coordinator, CityMatCH; Aislinn Rookwood, MPH, program manager, Health Promotion; doctoral student, UNMC; and Hana Niebur, MD, assistant professor, Pediatric Allergy/Immunology, UNMC, will present on their project, “A Qualitative Needs Assessment of Pediatric Asthma Care in the North Omaha Community.”
 
The mini-summit will conclude with a civic tech panel discussion, featuring:
  • Paul Darden, MD, Director, Population Health Research Program, Arkansas Children’s Research Institute, Professor of Pediatrics, Section of Primary Care, University of Arkansas for Medical Sciences
  • Ann Davis, PhD, MPH, ABPP, Ralph L. Smith Professor of Pediatrics and Director, Center for Children’s Healthy Lifestyles & Nutrition, University of Kansas Medical Center
  • Ellen Kerns, PhD, Assistant Professor, Child Health Policy, UNMC; Data Scientist, Children’s Hospital & Medical Center
  • Michelle Warren, PhD, Associate Professor, Spanish; Senior Advisor to the Chief Resource Officer, UNK

Pediatric Academic Workshop:
From Question to Publication,
through Medical Informatics
Friday, August 12 - 8 a.m. to 4 p.m.
Would you like to learn how to address your research question with the use of large health information databases?

Do you aspire to see your research published in peer-reviewed publications?

Join in the next semi-annual Pediatric Academic Workshop for tutorials on leveraging institutional databases and how to navigate reporting your study in a journal manuscript. These segments and an additional segment on Promotion & Tenure will be available to all registrants either in-person or via Zoom.

The workshop will also feature the popular paper-in-a-day active learning model, which invites participants to team up as co-authors on a real project. Take note - the Paper in a Day exercise is in-person and limited to the first 15 registrants. Please only sign-up, if you are certain that you will be able to attend. 

Event Details:
When: August 12 from 8:00 AM to 4:00 PM
Where: Children's Hospital & Medical Center, Indian Hills East conference facility
Format: Hybrid, with portions of the agenda available remotely (see below)

Agenda

8:00-9:00am Children’s Grand Rounds: Hybrid – Available to all Registrants

9:00-10:30am Workshop Sessions: Hybrid - Available to all Registrants
  • Opening Workshop Presentation
  • How to work with a Technical Writer
  • How to Research your References

10:45am-2:00pm Paper in a Day Interactive Exercise: In person only and limited to the first 15 registrants

2:00-3:15pm Promotion & Tenure Presentation and Panel Discussion: Hybrid - Available to all Registrants)

3:15-4:00pm Potential In-person Social Hour 

Please note: If you just plan on attending the Promotion and Tenure presentation and panel discussion, we ask that you register for the event so that we can provide you with the Zoom information needed to attend.
CHRI National Scientific Advisory Board Member Among Speakers at Global Health Panel at AAP National Conference and Exhibition
Save the Date 10/7/22, 2:00 to 4:00 p.m.

Well Established Career Neonatologists (WECaN) will be holding a panel discussion titled, "Going Global," at the American Academy of Pediatrics National Conference and Exhibition (NCE) on Oct. 7, 2022. The panel will feature Sara Berkelhamer, MD, associate professor of Pediatrics, University of Washington; Carl Bose, MD, professor of Pediatrics, University of North Carolina, School of Medicine and Child Health Research Institute National Science Advisory Board Member; George A. Little, MD, emeritus professor of Pediatrics, Dartmouth Geisel School of Medicine; William J. Keenan, MD, professor of Pediatrics & OB/GYN, Saint Louis University School of Medicine; and Yvonne Vaucher, MD, professor of Pediatrics, University of California San Diego School of Medicine.
Disseminating Discoveries:
May Publications
Take a minute to check out the wide range of research published by CHRI members in May.
Funding Opportunities:
Request for Innovative Pediatric Cancer Research Applications
Funder: Kate Amato Foundation
Amount: $25K-50K for pre-clinical laboratory trials
Deadline: August 1, 2022
More information: Click here
 
Opportunity Type: Request for Pilot-Project Applications
Research Topic/Areas: Cognitive Neuroscience of Development & Aging Center (CoNDA)
Deadline: 5:00 PM Monday, July 18, 2022
Budget Amount: Up to $50,000 per year
Budget Period: 1-2 years
Eligibility: UNMC, UNO, Creighton & Boys Town Faculty
Relevant Areas of Research: This mechanism aims to support innovative, collaborative projects in the field of neuroscience in general with emphasis on the cognitive neuroscience in development and aging in health and disease. Pilot Projects focused on the below issues are of high interest to the CoNDA Center. Applications proposing the study of animal models or human subjects will be considered.
For complete instructions, guidelines, ongoing CoNDA pilot Projects, and links to forms visit Cognitive Neuroscience of Development and Aging 2022 Request for Pilot-Project Applications
Child Health Research Institute
986847 Nebraska Medical Center
Omaha, NE 68198-6847
402-559-4032 or 402-955-7907