Research Update

August 2017

Dr. Alan Tackett to Establish Center for Translational Pediatric Research with New $11.5 Million NIH COBRE Award

Dr. Alan Tackett, an ACRI expert in systems biology, is the Scharlau Family Endowed Professor of Cancer Research and a professor of Biochemistry, Pediatrics and Pathology at the University of Arkansas for Medical Sciences (UAMS).

The National Institutes of Health (NIH) awarded $11.5 million to the Arkansas Children’s Research Institute (ACRI) to develop the Center for Translational Pediatric Research (CTPR). The award is the largest-ever grant award that ACRI has received from NIH.  Under the direction of Alan Tackett, PhD, the center will result in new treatments and therapies developed specifically for children.

Dr. Tackett, an ACRI expert in systems biology, is the Scharlau Family Endowed Professor of Cancer Research and a professor of Biochemistry, Pediatrics and Pathology at the University of Arkansas for Medical Sciences (UAMS).

The Center for Translational Pediatric Research at ACRI will use state-of-the-art technology and a systems biology approach to study how pediatric diseases develop, with the ultimate goal of identifying points in the intersection of disease and development that will produce targets for therapeutic intervention and the development of new treatments for children.

Systems biology is a holistic approach that enables researchers to simultaneously study all of the events occurring in a cell that are leading to a particular outcome or disease.

"Historically, science has answered one question at a time," Dr. Tackett said. "By employing a more comprehensive systems biology approach, we can ask many questions at the same time, which allows us to more quickly understand the fundamental reasons that a disease is occurring and how to more specifically develop treatments.

"To my knowledge, there is not a pediatric research center in the U.S. and probably in the world that focuses on utilizing these specific approaches. In that way, we are uniquely positioned to develop ways to improve children's health in Arkansas and our nation."

The NIH Institutional Development Award (IDeA) program will fund the CTPR as one of NIH's prestigious Centers of Biological Research Excellence (COBRE). These grants create world-class research environments for young faculty who are identified as the next generation of excellence in research. The awards focus on building research in states that have historically had low levels of NIH funding. This first phase of COBRE funding will start in July of 2017 and last five years. A total of 15 years of funding is available through this federal program, and Tackett’s award is the second COBRE grant ACRI has received from NIH in the last year.

"This award is a promise to the children of Arkansas that we will create a healthier tomorrow specifically for them," said Gregory Kearns, PharmD, PhD, FAAP, president of ACRI and Arkansas Children's senior vice president/chief research officer. He is also the Ross & Mary Whipple Family Distinguished Research Scientist Endowed Chair and a professor of Pediatrics at UAMS. "NIH sees that we have the potential to create a transformational center that will improve children's lives directly where they live, learn and play."

Dr. Tackett will serve as director of the CTPR and Sonet Weed, MS, will oversee the administration of the grant. The junior faculty that were selected to seed this center include:

• Jason Farrar, UAMS assistant professor of Pediatrics

• Xiawei Ou, PhD, UAMS assistant professor of Radiology and Pediatrics

• Laxmi Yeruva, PhD, UAMS assistant professor of Pediatrics

• Boris Zybailov, PhD, UAMS assistant professor of Biochemistry & Molecular Biology

Their research focuses on pediatric blood disorders, infant brain development in obese mothers, immune system development in breastfed infants, and pediatric chronic kidney disease – respectively.

All-in-all, the Center for Translational Pediatric Research will support 30 faculty – making it one of the largest centers of its kind. Located at ACRI, the CTPR will also partner with the Arkansas Children’s Nutrition Center and UAMS and its Winthrop P. Rockefeller Cancer Institute. The cutting-edge research technology investment will create discoveries in proteomics, genomics, and bioinformatics – overseen by:

• Rick Edmondson, PhD, UAMS associate professor of Medicine

• Samuel Mackintosh, PhD, UAMS research assistant professor of Biochemistry & Molecular Biology

• Stewart MacLeod, PhD, UAMS assistant professor of Pediatrics

• Stephanie Byrum, PhD, UAMS research assistant professor of Biochemistry & Molecular Biology

• Galina Glazko, PhD, UAMS assistant professor of Biomedical Informatics

To learn more about the program, visit http://www.archildrens.org/research/research-programs-and-centers/translational-pediatric-research/translational-pediatric-research

Summer Science Program 2017

This year’s Summer Science Program toured Transport Medicine including an up-close look at Angel One.

This summer, the UAMS Department of Pediatrics/Arkansas Children’s Research Institute (ACRI) Summer Science Program provided 23 outstanding students the experience of a career in academic medicine—in both the clinical and the research aspects. These students spent June and July in paid, research-related positions with ACRI researchers, conducting mentored research projects involving children’s health. The Summer Science Program also presented opportunities to attend rounds and clinics and to tour different hospital units. Faculty from various pediatric subspecialties taught basic science and clinical research techniques and helped the students gain exposure to clinical medicine. In addition, the Summer Science Program hosted a twice-a-week lecture series focusing on various aspects of academic medicine, graduate school, medical school, residency, research, and clinical medicine for its participants. At the end of the program, each student gave a scientific presentation on his or her research project.

Shelby Worsham (left) studied the effects of a pesticide on the cells of autistic children under the direction of Dr. Shannon Rose (right).

Shelby Worsham - Episcopal Collegiate School

Speaking about her Summer Science Program mentor, Episcopal Collegiate School senior Shelby Worsham said, “Dr. Rose answered all my questions,” then adding almost apologetically, “and I have lots of questions.”

“Shelby asked a lot of questions,” noted Dr. Shannon Rose, “but that’s what science is.”

Shelby, a Stella Boyle Smith Summer Scholar, conducted her research project in the ACRI laboratory of Dr. Rose, Pediatric Clinical Pharmacology. Dr. Rose studies the effects of environmental factors on mitochondria in relation to neurodevelopmental conditions, particularly autism spectrum disorder. Under Dr. Rose’s guidance, Shelby tested a theory that protein content of the mitochondrial electron transport chain will differ among control cells and cells from children with autistic disorder and that mitochondrial function of these cells will be altered by exposure to chlorpyrifos, a pesticide linked to autism. To conduct the project, Shelby learned how to perform western blotting, a technique used to separate and compare the relative content of specific proteins between samples and how to read the results with specialized software. She compared the content of five essential mitochondrial proteins between the samples to reach her conclusions. During the final week of the program, Shelby made a formal presentation to fellow Summer Science Students and to ACRI research faculty.

“The experience will help with research in college,” said Shelby, who is considering many colleges where she will study biology and chemistry in preparation for medical school.

In addition to exposure to pediatric medical research, the Summer Science Program also provides experiences for the students in clinical medicine. A prominent clinical experience for Shelby was spending the day with Dr. Richard Frye, Director of the Autism Multispecialty Clinic at ACH. Beyond connecting the clinical and research aspects of autism, Shelby gained more insight into the children with autism and other diverse abilities she works with through a Saturday tennis program she created, Amazing Children Empowered through Tennis (ACE Tennis).

“Dr. Rose always did her best to help me, and I was comfortable going to her with questions,” said Shelby. As a past Summer Science Program participant herself, Dr. Rose knows the importance of a positive hands-on opportunity where questions are asked and answers are pursued: “It’s an honor to be able to provide these experiences to young bright students like Shelby.”

Tyler Graham (right) studied the effects of digested fat in gut microbial ecology under the direction of Dr. Kartik Shankar (left).

Tyler Graham - Arkansas Technical University

For Tyler Graham, the Summer Science Program confirmed his academic and career goals. The Arkansas Technical University junior is studying biology and chemistry and intends to attend medical school, UAMS specifically, and to become a pediatric cardiovascular surgeon. Tyler met Dr. Takeshi Shinkawa, an ACH cardiovascular surgeon. Dr. Shinkawa and nurses in the cardiovascular unit took time to discuss and showcase their work with Tyler. “It was everything I thought it would be,” Tyler said, and as far as his goals, “the experience strengthened it.”

Tyler’s involvement in the Summer Science Program introduced him to medical research. Tyler conducted his research project in the laboratory of his mentor, Dr. Kartik Shankar, Developmental Nutrition. In Dr. Shankar’s laboratory at the Arkansas Children’s Nutrition Center, Tyler examined how different types of digested fat affect gut microbial ecology, which may influence a person’s disposition to obesity and metabolic disease. In the experiment, mice were fed diets of varying fat composition, and then the gut contents underwent microbial ecology analysis. Tyler collaborated with researchers with expertise in genomics and bioinformatics. “I saw it takes lots of collaboration to make a project work,” Tyler said, adding, “everyone in the lab has helped answer questions.”

Tyler noted that Dr. Shankar was a fantastic mentor: “I felt I had his backing and given guidance and freedom.” Dr. Shankar has annually participated as a mentor in the Summer Science Program: “Mentoring is a very critical cornerstone of academic research and is not only rewarding as a mentor but also a unique opportunity to think about fundamental scientific questions in a new way. Being a mentor is a privilege.”

Dr. Shankar remarked that he wants his students to leave the program thinking about research as a true career option. He felt Tyler not only has a positive attitude and willingness to learn, but also has a passion about what he wants to pursue. After his involvement with the Summer Science Program, Tyler said, “I can definitely see research as part of my career.”

ACRI President Dr. Greg Kearns (left) presents Tyler Graham (right) an award for first place for the Most Outstanding Presentation among college students.

Summer Science Program Awards

At the end of the Summer Science Program, each student gave a scientific presentation on his or her mentored research project. Awards are presented to two outstanding presentations by college students and to an outstanding presentation by a high school student.

This year among college students, Tyler Graham, a junior at Arkansas Technical University who was mentored by Dr. Kartik Shankar, Developmental Nutrition, was awarded first place for the Most Outstanding Presentation, “Types of Fats Impact on Gut Microbial Ecology,” and he received a $500 prize. Second place was won by Abbi Tatum, a senior studying biology at the University of Arkansas, who was mentored by Dr. Jeff Moran of PinPoint Laboratories for her presentation “Validation of Clinical Method for the Detection of MAB-CHMINACA and its Primary Human Metabolites in Human Blood and Urine.” She received a $250 prize. The awards for the most outstanding presentations by college students are generously sponsored by Dr. Gresham Richter, Pediatric Otolaryngology–Head and Neck Surgery.

Among the high school participants, Episcopal Collegiate School senior and Stella Boyle Smith Summer Scholar Samuel Rhee won for Most Outstanding Presentation for his project “Communication in a Large Academic Health Center.” His mentor was Dr. Wendy Ward, Pediatric Psychology and Associate Director of Faculty Affairs. The award for the most outstanding presentation by a high school student is munificently provided by Dr. Greg Kearns, President of ACRI.

About the Summer Science Program

Dr. Robert Fiser, Chairman of the Department of Pediatrics (1975 to 1994), created the Summer Science Program in 1989 to encourage Arkansas college students to pursue careers in medicine and science. Initially, a few college students worked in various research laboratories in the department. Throughout the history of this program, it has been funded using seed money from drug companies, then private companies and a pediatric clinic, and currently through the UAMS Department of Pediatrics, Arkansas Children’s Research Institute, and the Stella Boyle Smith Trust (which sponsors two Stella Boyle Smith Summer Scholars from Episcopal Collegiate School)—testimony to the broad range of research and clinical support for this program.

Jenny Kubacak is the Coordinator of the Summer Science Program. Since 1992, approximately 300 students and over 100 pediatric research faculty members have participated in the program. This year, the program selected its participants from nearly 120 applications and received the support of 26 faculty members serving as mentors. The Summer Science Program has an application deadline of February 28, 2018, for next year’s participants. 

President's Choice Publications

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

  • Blossom SJ, Melnyk SB, Li M, Wessinger WD, Cooney CA.  Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure.  Neurotoxicology. 2017 Mar;59:164-174.
     
  • O'Brien KA, Farrar JE, Vlachos A, Anderson SM, Tsujiura CA, Lichtenberg J, Blanc L, Atsidaftos E, Elkahloun A, An X, Ellis SR, Lipton JM, Bodine DM.  Molecular convergence in ex vivo models of Diamond-Blackfan anemia. Blood. 2017 Jun 8;129(23):3111-3120. 

Meet the Researcher:  Shannon Rose, PhD

Dr. Shannon Rose, Assistant Professor, Department of Pediatrics, Section of Clinical Pharmacology

How did you become involved in pediatric research?

My first experience with pediatric research was actually through the Summer Science Program which I participated in when I was in college. A year later, I worked here as a technician in Dr. Jill James’ autism research lab, and then I did my doctoral studies in her lab.

What types of sponsors (industry, federal, foundations, etc.) support your studies?

My studies are supported by the Marion B. Lyon New Scientist Development Award and the ACRI/Arkansas Biosciences Institute (ABI).

What is your area of study?

I study cellular bioenergetics, which is essentially the ways in which cells make energy. I am interested in the effects that certain environmental exposures have on the mitochondria as well as how bioenergetic pathways are disrupted in neurodevelopmental disorders such as autism as well as metabolic disorders like obesity and type 2 diabetes. Using the Seahorse XF96, which is a technology known as multi-well extracellular flux analysis to measure mitochondrial oxygen consumption in intact living cells, allows me to study the mitochondria in the context of the cellular microenvironment, rather than in isolation. A major goal of my research is to determine whether bioenergetics of circulating blood cells can be used as surrogate biomarkers for systemic inflammation and metabolic dysfunction.

How is your research program innovative?

The non-invasive approach of measuring blood cell bioenergetics to identify metabolic dysfunction in pediatric populations is innovative.

How has your work led to (or will lead to) changes in pediatric care?

The goal is that to one day use circulating blood cell bioenergetics as biomarkers of disease or disease risk.

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

I continue to collaborate with my doctoral and postdoctoral mentors, Drs. Jill James and Richard Frye. For my obesity studies, I collaborate with Drs. Eugenia Carvalho, Elisabet Borsheim, and Jon Oden. These collaborations are important because they enhance my ability to answer my research questions through sharing resources and expertise, and they facilitate “big-picture” thinking.

Recent Clinical Trials Activity

PI

Agency

Project Description

Project Period

Total Cost

Vijayan, Vini

Merck

MK7655

6/17 -

$51,655

Courtney, Sherry

Mallinckrodt

PATTERN

6/17 -

$42,401

Berlinski, Ariel

Anthera

RESULT

6/17 -

$121,748

Scurlock, Amy

Aimmune

ARC007

6/17 -

$238,689

Hutchison, Michelle

Ascendis

TransCon

6/17-

$85,310

Mercer, Kelly

Enzymotec

ACNC

6/17 - 12/17

$45,000

Sharp, Gregory

GW Pharma

Infantile Spasms

6/17 -

$115,093

Sharp, Gregory

UCB

Epilepsy

6/17 -

$159,165

Romero, Jose

UCSF

Kawasaki

2/17 - 1/18

$16,100

Jones, Stacie

Astellas

MATRIX

6/17 -

$219,697

Kimo Stine

Sangamo

Hemophilia A

7/1/17 -

$91,008

Kimo Stine

Dimension

Hemophilia A

7/1/17 -

$20,749

Recent Grant Activity

Extramural Grant Awards 

PI

Agency

Project Title

Project Period

Total Funding

Kartik Shankar NIH

Epigenetic Mechanisms Underlying Trophoblast Syncytialization

8/1/17-7/31/19

$420,750

Alan Tackett

NIH

Center for Translational Pediatric Research

7/17-6/22

$11,475,000

Extramural Grant Application Submissions 

PI

Agency

Project Title

Project Period

Total Funding

Charlotte Hobbs

NIH sub Indiana University

Gene-by-Gene and Gene-by-Environment Interactions Underlying CHDs

4/18-3/20

$35,193

Reza Hakkak

USDA

Obesity, Gut Microbiota and Non-Alcoholic Fatty Liver Protection in Adolescents and Adults by Soy Protein Diet

4/18-3/21

$498,581

Richard Kurten

NIH sub La Jolla Institute for Allergy and Immunology

LIGHT/TNFSF14 in allergic esophagitis remodeling

4/18-3/23

$306,000

Rosemary Nabaweesi

American SIDS Institute

Developing Tailored Safe Sleep Interventions for Rural Underserved Communities

1/18-12/19

$55,885

Kartik Shankar

NIH / U of Kansas Medical Center -Subaward

Maternal Obesity-Associated Programming of Liver Disease

4/2018-3/2023

$2,291,267

Intramural Grant Program Awards

PI

Project Title

Project Period

Total Funding

Joana Mack

Analyzing Coagulation Dynamics in Vascular Malformations with Thromboelastography

8/2017-6/2018

$15,000

Megan Patterson

Effects of Swallowed Corticosteroids on Bone Mineral Density and Growth Velocity in Children with Eosinophilic Esophagitis

8/2017-7/2018

$9,340

Jennifer Rumpel

Early Diagnosis of Acute Kidney Injury using Urinary Biomarkers and Renal Oximetry in Neonates with Hypoxic Ischemic Encephalopathy

7/2017-6/2019

$15,000

Intramural Grant Program Submissions (ACRI-ABI Investigator Initiated Grant Program)

PI

Project Title

Project Period

Total Funding

Sarah Blossom

Reprogramming Obesogen-Induced Neurologic Effects by Dietary Intervention. 

10/2017-9/2019

$75,000

Laura Hays

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

10/2017-9/2018

$19,702

Stepan Melnyk

Biomarkers Discovery to Detect Metabolic Subtypes within the Autism Spectrum Disorder

10/2017-9/2018

$75,000

Tamara Perry

Telehealth Enhanced Asthma Management (TEAM)

10/2017-9/2019

$75,000

Gresham Richter

Finding Treatments for Arteriovenous Malformations through Sequencing and Data Mining

10/2017-9/2019

$75,000

Xinyu Tang

Application of Whole Exome Sequencing in Obstructive Heart Defects: A Pilot Study

10/2017-9/2019

$75,000

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