Research Update

October 2017

NIH Awards R21 Grant to Dr. Kartik Shankar

In August, the National Institutes of Health notified Dr. Kartik Shankar, Associate Professor of Pediatrics and Associate Director of Basic Research at the Arkansas Children’s Nutrition Center, of an R21 funding award for his proposal, “Epigenetic Mechanisms Underlying Trophoblast Syncytialization.”

This new exploratory research project funded by the National Institute for Child Health and Development is focused on understanding how the placenta forms in pregnancy. The 2-year, $420,000 project will focus on understanding a specific epigenomic pathway involved in the formation of placental cells that mediates the transfer of nutrients and gases from mother to child. The epigenome is akin to a computer's software program that directs different pieces of hardware (our DNA) to be either engaged or silenced. The placenta is the very first organ that a baby develops in the womb and serves as the only link between the developing child and the mother. “Certainly how we grow in the womb has life-long consequences for health, and the health of the placenta affects numerous outcomes throughout life,” said Dr. Shankar, “so fundamental aspects of placentation are critically important to understand for child health.”

Dr. Shankar has current research grant support through the ACNC’s USDA-Agricultural Research Service funding, which also supported preliminary investigations for this project. In addition, funds from the ACRI F&A Match program were also critical in supporting the project.

TRI Names Dr. Rosemary Nabaweesi as a New KL2 Scholar

Rosemary Nabaweesi, DrPH, MBChB, MPH, Assistant Professor, CARE, has received KL2 Mentored Research Career Development Scholar Award from the UAMS Translational Research Institute (TRI). Her project is “Developing Safe Sleep Interventions for Rural Underserved Communities.”

The KL2 Scholar program provides two years of didactic and mentored research training to junior faculty who are committed to academic careers in multidisciplinary clinical or translational research. Those selected for the program receive 75% salary support and up to $25,000 per year for research, tuition, travel expenses, and education materials. In addition to TRI's funding, support for this KL2 cycle is also provided by Arkansas Children's Research Institute and the Department of Psychiatry in the College of Medicine. Dr. Nabaweesi is one of four scholars chosen for a KL2 award from a strong pool of fifteen applicants.

Arkansas Children’s Debuts Region’s Only Pediatric Exercise Science Lab

In October, the Arkansas Children's Nutrition Center (ACNC) Laboratory for Active Kids and Families held its open house. At the new laboratory, located on the first floor of the ACNC, researchers will test and study children and pregnant women to better understand the science of exercise and the mechanisms which physical activity promotes health. The open house was attended by Arkansas Governor Asa Hutchinson, Lieutenant Governor Tim Griffin, and UA System President Donald Bobbitt. ACNC Senior Investigator Dr. Elisabet Børsheim is the director of the laboratory, and researchers and staff provided tours which included demonstration of equipment by children participating in studies at the ACNC.

The Laboratory for Active Kids and Families will allow researchers to conduct a variety of physical and biological testing. Sophisticated equipment can measure ventilation, gas exchange, lung volumes and other physiological parameters. The facilities also include specialized bikes, treadmills, weight machines, and other equipment to measure endurance, strength, balance, flexibility, energy expenditure, and other physical components. The new laboratory is further equipped to sample blood, urine, and saliva. In addition, children and families will be able to complete questionnaires on lifestyle (e.g., diet and physical activity) and household and environmental factors that may affect health.

As the rates of pediatric obesity in Arkansas are among the highest, the Laboratory for Active Kids and Families is positioned to support efforts to increase childhood physical activity and to develop interventions to improve children’s health. With the availability of this laboratory and its resources, it has an important role in addressing the state’s childhood obesity challenges and in supporting Arkansas Children’s commitment to improve the health of children throughout the state.

As children of obese mothers may be predisposed to obesity, an ongoing study at the ACNC by Dr. Børsheim and Dr. Aline Andres tests children born to lean, overweight, or obese mothers for endurance and strength in the laboratory. In another large study, obese sedentary women are randomized to standard of care or exercise training during pregnancy. Their fitness levels are tested before and after training, and the investigators will determine if training through pregnancy can attenuate negative effects of obesity on the mother and their babies.

In a USDA-funded study led Dr. Børsheim and Dr. Judith Weber, 200 children will go through a battery of exercise tests combined with assessment of other metabolic variables to determine the independent impact of weight status, physical activity, and physical fitness, respectively, on overall cardiometabolic health. The study will also identify household, environmental, and socio-demographic factors associated with weight status and metabolic health.

The Laboratory for Active Kids and Families was created with funds from the USDA-Agricultural Research Service to the ACNC. The laboratory is one of only a handful in the world that focuses on childhood exercise physiology. Established in 1994, the ACNC is one of six National Human Nutrition Centers funded through and cooperating with the USDA-ARS. It operates in close collaboration and partnership with ACRI as part of the Arkansas Children’s research enterprise with the mission to conduct cutting-edge research to understand how maternal-child nutrition and physical activity optimize health and development. 

Read the full Arkansas Children’s media release here.

Arkansas Children’s Nutrition Center Awarded $7.4 Million to Fund Groundbreaking Research on Development, Childhood Obesity and Disease Prevention

The Arkansas Children’s Nutrition Center (ACNC) will receive $7.4 million from the United States Department of Agriculture (USDA) through its Agricultural Research Service (ARS) to fund research in the areas of child development, maternal health and disease prevention. The funding will continue the center’s 23-year history of innovative research into how nutritional status, physical activity and dietary factors shape human development and influence susceptibility to childhood diseases, as well as those illnesses that initiate early in life but do not appear until adulthood. “At ACNC, our faculty and staff have a single motivation,” Dr. Sean Adams, ACNC director and professor of Pediatrics, said, “Improving the health and well-being of families, and figuring out which factors drive optimal child development and prevention of disease. This is right in line with the missions of USDA-ARS and Arkansas Children’s, giving immediate impact to the team’s research.” Read the full Arkansas Children’s media release here.

Six Inaugural Groundbreaking Projects Funded through the Center for Childhood Obesity Prevention at Arkansas Children's Research Institute

The Center for Childhood Obesity Prevention has announced its first wave of NIH-funded projects to help make children better today and healthier tomorrow. “These first six projects reflect the mission of the Center to examine and address issues related to childhood obesity at all levels, including developmental causes, therapeutic treatments, and translation of findings directly to children and their families wherever they reside in Arkansas,” said Dr. Judith Weber, director of the multidisciplinary center and professor of Pediatrics. The Center for Childhood Obesity Prevention was established in 2016 with a $9.4 million NIH Centers of Biomedical Research Excellence (COBRE) grant award to ACRI. Read the full Arkansas Children’s media release here.

Center for Translational Pediatric Research Announces Pilot Project Program Recipients

The Center for Translational Pediatric Research has announced the recipients of its Pilot Project Program awards. Dr. Yasir Rahmatallah, Biomedical Informatics, and Dr. Joshua Kennedy, Allergy and Immunology, have each received $75,000 for one year in direct costs for their pilot projects.

Dr. Rahmatallah’s project, “Integrating Gene Expression Profiles from Different Platforms into a Robust and Clinically Relevant Prognostic and Predictive Tool for Pediatric Leukemia,” will use a novel computational approach integrating RNA-seq and microarray expression profiles of unmatched samples to find expression signatures with clinical prognostic relevance to pediatric B-cell acute lymphoblastic leukemia and acute myeloid leukemia patients. The proposed approach will reduce platform-specific biases and heterogeneity between samples that impaired previous efforts to increase reproducibility and confidence in the resulting prognostic tools.

Dr. Kennedy’s project, “A Systems Analysis of Airway Hyper-responsiveness in Precision Cut Slices from Donors with Asthma,” will compare airway hyperresponsiveness in human airways precision-cut lung slices from donors with a Th2-high signature to those with Th2-low signature in airway epithelial cells is determine if different pathways may be involved with regard to the airway hyperresponsiveness during RV infection. He will use a systems biology approach, utilizing transcriptomics, proteomics and integrated bioinformatics, to evaluate differences between groups.

The focus of the Center for Translational Pediatric Research (CTPR) is to investigate how pediatric diseases develop using systems biology and mechanistic approaches, with the ultimate goal of identifying the intersections of disease and development. Systems biology is an integrated approach examining all events within cells, tissues, and organisms that lead to a particular outcome. By applying a systems biology approach to the study of pediatric diseases, the CTPR hopes to expand existing knowledge of pediatric disease development and identify new targets for the development of therapeutics. The CTPR Pilot Project Program will provide funding to junior faculty at Arkansas Children’s and UAMS campuses to generate data for publications and NIH proposals.

Researcher Spotlight:  Brian Piccolo, PhD

Dr. Piccolo is an Assistant Professor in the Department of Pediatrics at UAMS and researcher in the Arkansas Children’s Nutrition Center.  

How did you become involved in pediatric research?

Establishing healthy eating and lifestyle practices early in life is the best way to prevent obesity and metabolic diseases in adulthood, so it was a no-brainer to take this opportunity when it was available. It is a great feeling knowing that my research can reduce the risk of obesity throughout the lifespan rather than reactive research approaches in more adult-centered care.

What types of sponsors support your studies?

My research is primarily supported by the USDA-Agricultural Research Service, with additional support from ACRI intramural grants (CUMG), the Sturgis Foundation, and the American Society for Metabolic and Bariatric Surgery.

What is your area of study?

My laboratory has two areas of focus: 1) understanding the influence of host energy regulation on the composition and function of the gut microbiota population, and 2) developing interactive web-based apps for “Big Data” analysis and visualization.

How is your research program innovative?

The gut microbiome is arguably the current hot topic in nutrition research, but the majority of nutritional-based studies are investigating diet-specific alterations in the composition of the microbiome. For our studies, we are coupling microbiome and metabolomics data to pinpoint metabolic pathways that could explain a functional interaction between the microbiome and the host. We feel that this could lead to focused interventions and modulation of the gut microbiome to improve health and lessen disease risk.

How will your work lead to changes in pediatric care?

By using cutting edge technology, we feel our research will help pediatrics care providers rapidly identify important bacterial signatures that when combined with other phenotypic traits could guide care and disease prevention in kids.

Who do you collaborate with and what are the benefits of these collaborations?

I collaborate closely with Drs. Laxmi Yeruva and Kartik Shankar at the ACNC. We all share a high interest in the gut microbiota and have unique skills that complement each other. Additionally, I work with the ACNC Informatics Team, Drs. Sree Chintapalli and Sudeepa Bhattacharrya, to promote and increase the bioinformatics capabilities of the ACNC.

What are some of you recent research activities and achievements?

We have recently released DAME (Dynamic Assessment of Microbial Ecology), a new interactive web-based app for microbiome data analysis and visualization. DAME is easy to use and provides researchers the flexibility to assess several indices of alpha and beta diversity at all taxonomical levels concurrently. DAME also calculates differential abundance of individual taxa at all taxonomic levels using the most advanced statistical techniques. All tabular and graphic outputs update in real time and are completely interactive. DAME is available at https://acnc-shinyapps.shinyapps.io/DAME/ and is completely free to use.

President's Choice Publications

The following articles were selected as this month's feature publications.

  • Gore L, Triche TJ Jr, Farrar JE, Wai D, Legendre C, Gooden GC, Liang WS, Carpten J, Lee D, Alvaro F, Macy ME, Arndt C, Barnette P, Cooper T, Martin L, Narendran A, Pollard J, Meshinchi S, Boklan J, Arceci RJ, Salhia B. A multicenter, randomized study of decitabine as epigenetic priming with induction chemotherapy in children with AML. Clin Epigenetics. 2017 Oct 5;9:108. doi: 10.1186/s13148-017-0411-x. eCollection 2017.

  • Gupta P, Chakraborty A, Gossett JM, Rettiganti MA prognostic tool to predict outcomes in children undergoing the Norwood operation. J Thorac Cardiovasc Surg. 2017 Aug 30. pii: S0022-5223(17)31795-6. doi: 10.1016/j.jtcvs.2017.08.034. [Epub ahead of print]

New Grant Awards

Extramural Awards

PI

Agency

Project Title

Project Period

Total Funding

Sudeepa Bhattacharyya

NIH/Duke

Metabolic Networks and Pathways in Alzheimer’s Disease

8/17 - 5/18

$29,800

Sherry Courtney

NIH/Albert Einstein College of Medicine

Developmental Impact of NICU Exposures (DINE) UG3 Study Environmental Influences on Child Health

9/16 - 8/18

$5,000

Judy Weber

Bank of America

2017.2018 Bank of America

9/17 - 8/18

$7,500


Intramural ACRI/ABI Grant Program Awards

PI

Project Title

Project Period

Total Funding

Sarah Blossom

Reprogramming obesogen-induced neurologic effects by dietary intervention

10/17-9/19

$75,000

Laura Hays

Self-Reported Self-Management of Adults with Congenital Heart Disease

10/17-9/19

$19,702

Stepan Melnyk

Biomarkers Discovery to Detect Metabolic Subtypes within the Autism Spectrum Disorder

10/17-9/19

$75,000

Tamara Perry

Telehealth Enhanced Asthma Management (TEAM)

10/17-9/19

$75,000

Gresham Richter

Finding treatments for Arteriovenous Malformations through sequencing and data mining

10/17-9/19

$75,000

Recent Grant Proposal Submissions

PI

Agency

Project Title

Project
 Period

Total
 Funding

Aline Andres

NIH/Harvard

Phthalates, fat accretion and cardiometabolic health in early life

7/18-6/23

$341,575

Aline Andres

NIH/U of Kansas Medical Center

Growth and adiposity in newborns: the influence of prenatal DHA supplementation

7/18-6/23

$43,187

Jin-Ran Chen

NIH 

Persistent effect of soy infant formula on bone formation in children

7/18-6/23

$3,333,499

Sherry Courtney

NIH/Albert Einstein College of Medicine

Developmental Impact of NICU Exposures (DINE) UG3 Study  Environmental Influences on Child Health Outcomes (ECHO) Program

9/16-8/18

$4,999

Richard Frye

NIH

Prenatal programming of mitochondrial function by environmental exposures

7/18-6/23

$3,818,313

Reza Hakkak

NIH

Soy Diet Microbiome Biomarkers of Obesity-linked Breast Cancer

7/18-6/23

$2,060,946

Rosemary Nabaweesi

NIH

Developing and Testing Safe Sleep Interventions in Rural Underserved Communities (K01)

7/18-6/22

$472,698

Kathleen Neville

NIH/CHB

Defining off-label and low-evidence medication prescribing in children to promote safety in ambulatory settings

7/18-6/21

$175,960

Kathleen Neville

NIH/Medical University of North Carolina

DISPLACE: Dissemination and Implementation of Stroke Prevention: Looking at the Care Environment

7/17-6/22

$189,999

Tamara Perry

NIH/U of Rochester

TEAM-UP

7/18-6/23

$46,123

Clinical Trial Activity

PI

Agency

Project

Project Period

Total Funding

Romero, Jose

Cephid

Flu/RSV

8/17 -

$58,900

Stine, Kimo

BioMarin

BMN270-901

9/17 -

$25,330

Hutchison, Michelle

Janssen

DIA3018

7/17 - 9/21

$87,985

Farrar, Jason

Novartis

CETB115

4/17 -12/24

$122,646

Schmitz, Michael

Braun

Ancef

8/17 - 7/18

$68,211

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