Intramural Pediatric Research Seminar Series (IMPRESS)

Infant Neurodevelopment and Connections to Gut Microbes

Speakers: 

Marie Swanson, MD
Assistant Professor,
Division of Neonatology
Department of Pediatrics
University of Minnesota

The idea that gut microbes are involved in brain function is known as the Gut-Microbiome-Brain Axis. Exciting research performed primarily in animal models up to this point in time supports the existence of this Axis. These preclinical models highlight the idea that infancy is a critical time window for microbial modulation of brain development. Longitudinal studies to investigate the potential contribution of gut microbes to early neurodevelopment in humans are needed. I will describe my observational and pilot intervention studies that aim to better understand the Gut-Microbiome-Brain Axis in infants who are at risk for microbiome disruption.

The Study of Caffeine in Preterm Hypoxic Ischemic Encephalopathy

Speakers: 

Rachel Koski, DO, MSc
Assistant Professor,
Division of Neonatology
Department of Pediatrics
University of Minnesota

Hypoxic ischemic encephalopathy (HIE) affects both term and preterm newborns. However, preterm infants are at a greater risk for HIE, and there are no approved treatment therapies for this age group to mitigate poor neurodevelopmental outcomes. Dr. Koski will present data from her preterm rat model exploring caffeine’s therapeutic effects following this brain injury and future directions.

Mitochondrial function in Netrin1/DCC- regulated neurodevelopment

Speakers: 

Thomas Bastian, PhD
Assistant Professor,
Division of Neonatology
Department of Pediatrics
University of Minnestoa

Tim Monko, PhD
Post-Doctoral Researcher
Bastian Lab

Zhe Chen, PhD
Assistant Professor
Department of Neuroscience

Dysfunction of mitochondria during fetal and child development has been increasingly recognized to be responsible for neurodevelopmental and psychiatric disorders. Our recent studies have revealed potential regulation of mitochondrial activity by the Netrin1/DCC (Deleted in Colorectal Carcinoma) signaling, which has critical functions during neurodevelopment and its dysregulation underlies some common disorders with mitochondrial dysregulation (e.g., developmental delay , schizophrenia, and autism spectrum disorder), . We will present our basic science research, supported by a Masonic Cross- Departmental Grant award, showing that mitochondrial activity contributes to Netrin-1/DCC regulation of neuronal development. We will further discuss novel research directions in the Bastian and Chen labs stimulated by this award.

Speakers: 

Rahma Ali
(Mentor: Dr. Jennifer Needle, Division of Critical Care)
Reimagining Language Equity: Defining Best Practices in Partnering with Informal Interpreters of Somali Families in the Neonatal Intensive Care Unit

Mahasweta Bose
(Mentor: Dr. Rebekah Hudock, Division of Clinical Behavioral Neuroscience)
Adaptation of the PEERS Social Skills Program for Individuals with Intellectual and Developmental Disabilities

Kimberly Clinch
(Mentor: Dr. Rachel Witt, Division of Neonatology)
NICU Breast-Milk-Feeding Equity Advancement and Research (NICU-BEAR)

Nhi Lang
(Mentor: Dr. Catherine Burrows, Division of Clinical Behavioral Neuroscience)
Examining how medical complexities impact the effect of psychological conditions (ADHD, anxiety) on executive functioning in children

Aarohi Shah
(Mentor: Dr. Varun Aggarwal, Division of Pediatric Cardiology)
Predictors of Complications during Cardiac Catheterization

Jacqueline Tobar Jimenez 
(Mentor: Dr. Anne White, Division of Neonatology)
Improving Global Equity and Access to High-Level Disinfection

Neurobehavioral Functioning and Neurocircuitry of Adolescents with Obesity

Speakers: 

Amy Gross, PhD, LP, BCBA
Associate Professor& Division Director, Division of Clinical Behavioral Neuroscience
Associate Director of Clinical Care, Center for Pediatric Obesity Medicine

Kelvin Lim, MD
Drs. T.J. and Ella M. Arneson Land-Grant Chair in Human Behavior
Professor, Director of Adult Mental Health Research
Department of Psychiatry and Behavioral Sciences

Adolescent severe obesity is a complex and difficult-to-treat disease. Understanding the neurobiological underpinnings of this intractable disease will enhance our understanding and support development of novel, effective interventions tailored to individual factors. Stemming from research supported by a Department of Pediatrics Progressive Award, we will present our neurobehavioral and neuroimaging findings in adolescents with average BMI compared to those with severe obesity. We will also discuss current and future directions of this work, including how the Progressive Award led to extramural funding and our continued collaborative efforts in novel assessment in youth with obesity.

The PS Gene Editing System: A Platform Technology for Treating Lysosomal Disorders

Speakers: 

Michael Przybilla, PhD
Assistant Professor, 
Division of Pediatric Genetics and Metabolism
Department of Pediatrics

The PS Gene Editing System (PSG System) is an AAV-based gene editing platform technology developed as a single-dose treatment for monogenic disorders, in particular lysosomal diseases. The PSG System employs CRISPR-Cas9 to generate a targeted double-stranded DNA break in the first intron of the albumin locus in hepatocytes. By providing a second AAV containing a donor template encoding a functional copy of the lysosomal enzyme cDNA, these hepatocytes effectively become an enzyme-producing factory. In this presentation, data will be presented that demonstrates the efficacy of this system as a therapeutic for lysosomal disorders such as GM1-gangliosidosis.

Early neuroimaging markers of cerebral adrenoleukodystrophy

Speakers: 

Rene Pierpont, PhD, LP
Associate Professor, 
Division of Clinical Behavioral Neuroscience
Department of Pediatrics
University of Minnesota

René Labounek, PhD
Division of Clinical Behavioral Neuroscience

As newborn screening is now available for X-linked adrenoleukodystrophy (ALD), there is a need to establish meaningful disease markers to detect the onset of the severe demyelinating cerebral form at the earliest possible stage and to quantify early disease progression. We show that diffusion tensor imaging (DTI) is sensitive to early, disease pattern-specific brain changes in patients with cerebral ALD and is associated with clinical neurocognitive outcomes after treatment with stem cell therapies. DTI is a promising method to support early detection and quantify treatment response to improve outcomes and quality of life patients with cerebral ALD.

3D Biofabrication: Applications to Cancer

Speakers: 

Angela Panoskaltsis-Mortari, PhD
Vice Chair for Research & Professor
Division of Pediatric Blood Marrow Transplantation & Cellular Therapy
Department of Pediatrics
University of Minnesota

Challenges and opportunities in advancing personalized care to manage late effects among survivors of childhood cancer 

Speakers: 

Cindy Im, PhD 
Assistant Professor, 
Division of Pediatric Epidemiology & Clinical Research
Department of Pediatrics
University of Minnesota

Lucie Turcotte, MD, MPH, MS
Associate Professor, 
Division of Pediatric Hematology and Oncology
Department of Pediatrics
University of Minnesota

Advances in treatments have dramatically improved long-term survival after childhood cancer to >85% in the US. However, childhood cancer survivors are at increased risk for experiencing severe and life- threatening health conditions as they age as a consequence of cancer therapy. Using a study of differences in treatment and mortality among childhood cancer survivors who developed subsequent breast cancer as an example, Dr. Lucie Turcotte will highlight the challenges in addressing survivors’ lifelong increased risk of multiple morbidity. Dr. Cindy Im will then discuss potential opportunities to facilitate personalized care, leveraging large epidemiological datasets, statistical/machine learning- based prediction modeling, and genetics to improve late effects clinical risk stratification.

Q-rounds: Lessons Learned From When Your Academic Product has Potential to be an Actual Product

Speakers: 

Michael Pitt, MD
Associate Chair for Faculty Development, Professor, Fellowship Program Director, & Associate Residency Program Director, 
Division of Pediatric Hospital Medicine
Department of Pediatrics
University of Minnesota

In this session, Dr. Mike Pitt, Professor in Pediatrics, will share a journey of how a frustration he'd noticed as a clinician and a loved one of hospitalized patients spawned a research question which has evolved into a software company. He'll share lessons learned in navigating the University when an academic product has the potential to be a marketable product, including discussing logistics of intellectual property licensing, balancing conflicts of interest (both real and perceived), raising money from grants and private investors, and finding collaborators. He'll also share results of their pilot in the neonatal intensive care unit that lead to a near tripling of nurse and family presence for rounds, and is helping make access to hospital rounds a right and not a privilege.

Searching for Balance: Bilirubin and the Preterm Brain

Speakers: 

Katherine Satrom, MD
Assistant Professor, 
Division of Neonatology
Department of Pediatrics
University of Minnesota

Troy Lund, MD, PhD
Professor & Fellowship Program Director, 
Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy
Department of Pediatrics
University of Minnesota

Jiuzhou Wang, 
Biostatistics PhD Candidate

We will identify the knowledge gaps in the management of neonatal jaundice in preterm infants and discuss how our research program seeks to understand the balance between bilirubin's toxic vs. beneficial effects. We will present data from our Gunn rat model of preterm hyperbilirubinemia as well as results from a unique metabolomics-based study looking at the effects of phototherapy on the plasma metabolite profile in preterm infants treated for jaundice.

SUPER Award Reception

Award Recipients:

Jenna Dick       
Targeting dysfunctional natural killer cells in Multisystem Inflammatory Syndrome in Children (MIS-C)

Lucas Dornan       
Mental health in pediatric germ cell tumor survivors

Nhi Lang       
Do medical complexities impact the effect of psychological conditions (ADHD, anxiety) on executive functioning in children?

Lay Lay       
Prenatal education for prevention of congenital infection in infants born to Karen Women

Dana Yang       
Generation of chemoresistant CIC0DUX4 sarcoma cell lines

tDCS and Cognitive Training as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorder

Speakers: 

Blake Gimbel, PhD
Postdoctoral Fellow
University of Minnesota

Investigators: 

Jeffrey R. Wozniak, PhD

Youth with fetal alcohol spectrum disorders (FASD) show differences in brain and behavior development, and attention and executive functioning are common areas of impairment. Novel interventions have the potential to favorably alter neurodevelopmental trajectories during critical periods of brain development. The purpose of the current study is to use mild brain stimulation (transcranial direct current stimulation [tDCS]) to augment a tailored cognitive training regimen targeting attention and working memory in youth with FASD ages 8-17 years. The current study builds on our group’s recent pilot RCT in children ages 9 to 16 with FASD, in which we demonstrated that this intervention was safe, well-tolerated, and led to greater improvements in attention performance compared to sham-tDCS.

Optimizing iron status while minimizing morbidity in HIV-infected Ugandan Children

Speakers & Investigators: 

Sarah Cusick, PhD 
Associate Professor, 
Division of Epidemiology and Clinical Research
Department of Pediatrics
University of Minnesota

Anne E.P. Frosch, MD, MPH  

Pediatric iron deficiency and human immunodeficiency virus (HIV) coexist in many regions of the world. Iron deficiency is an established cause of impaired cognitive and behavioral development, but iron is frequently withheld from anemic, HIV-infected children for fear of increasing opportunistic and other infections, although this practice is not evidence-based.

In a new era of widespread use and success of pediatric anti-retroviral regimens, children with HIV are living longer, healthier lives, and achievement of their full developmental trajectory is a new public health imperative. We will present the results of our recently completed, randomized, placebo-controlled clinical trial of iron in Ugandan children 6 months- 12 years with HIV and anemia, focusing on the effect of iron on iron status, incidence of infection, composition of the gut microbiome, and markers of inflammation.

Cytomegalovirus: A Ubiquitous Agent with Protean Clinical Manifestations, Well-Suited to Team Science Studies

Speakers & Investigators: 

Erin Osterholm, MD
Associate Professor,
Division of Neonatology
Department of Pediatrics
University of Minnesota

Mark R. Schleiss, MD
Professor,
Division of Pediatric Infectious Diseases
Department of Pediatrics
University of Minnesota

Previous research has suggested a higher rate of overweight and obesity in autistic children and adults. With the increased prevalence of both childhood obesity and autism spectrum disorder (ASD), it is important to investigate associations of obesity within the ASD population. The purpose of this study was to describe child characteristics and family feeding practices in families of children with ASD and their association with BMI and obesity.

A Descriptive Study of Child and Family Variables Related to Obesity in Autism Spectrum Disorder

Speaker: 

Stacey Brandjord, PhD, NCSP, CCC-SLP    

Investigators: 

Amy Esler, PhD, LP 
Associate Professor,
Division of Clinical Behavioral Neuroscience
Department of Pediatrics
University of Minnesota

Claudia Fox, MD, MPH
Associate Professor,
Division of Pediatric Gastroenterology, Hepatology, & Nutrition
Department of Pediatrics
University of Minnesota

Previous research has suggested a higher rate of overweight and obesity in autistic children and adults. With the increased prevalence of both childhood obesity and autism spectrum disorder (ASD), it is important to investigate associations of obesity within the ASD population. The purpose of this study was to describe child characteristics and family feeding practices in families of children with ASD and their association with BMI and obesity.

Exploring Novel Therapeutics for Pediatric and Adult Glioblastomas

Speakers: 

Okay Saydam, MSc, PhD
Assistant Professor,
Division of Pediatric Hematology & Oncology
Department of Pediatrics
University of Minnesota

Investigators: 

Okay Saydam, MSc, PhD and Gunda I. Georg, PhD

The current treatment of glioblastoma is based on a DNA-alkylating chemotherapeutic agent temozolomide (TMZ) that is administered after radiotherapy. When combined with radiation therapy, TMZ only increases the median survival rate of glioblastoma patients from 12.1 months to 14.6 months. However, the beneficial effect of TMZ is short-lived due to rapidly developing chemoresistance. DNA repair has been indicated as one of the critical factors contributing to mechanisms of chemoresistance in glioblastomas. We recently discovered that glioblastoma cells acquire drug resistance by switching to an alternative, effective DNA repair pathway called Homologous Recombination (HR). Rad51, a key factor in HR, plays a central role in the HR repair of double- strand DNA breaks (DSBs). We found that targeting Rad51 using a chemical inhibitor, B02, kills TMZ resistant glioblastoma cells. Our goal is to develop patentable derivatives of B02 and test their tumor killing effect in in vivo pediatric and adult glioblastoma mouse models with the ultimate goal to develop a clinical candidate.

Fetal-neonatal iron deficiency and prenatal choline supplementation alters chromatin accessibility and histone H3K9me3 landscapes in the adult rat hippocampus

Speakers: 

Shirelle Liu and Tenille Fredrickson    

Investigator: 

Phu Tran, PhD
Associate Professor,
Division of Neonatology
Department of Pediatrics
University of Minnesota

Fetal-neonatal iron deficiency (ID) results in long-term neurodevelopmental impairments with persistent hippocampal gene dysregulation, which implicates early-life ID-induced epigenetic alterations. Our previous work demonstrated that prenatal choline (a methyl donor) supplementation can partially reverse these behavioral and transcriptomic effects. Emerging evidence also suggests an interaction between iron and choline in regulating the hippocampal epigenome. Therefore, our lab is currently investigating how ID, choline supplementation, and their interaction affect the epigenetic landscape that could underlie the long-term gene dysregulation in the adult rat hippocampus.

The Gap in Early Life Immunity Between Nature and Conventional Laboratory Mouse Models

Speakers: 

Nathan Schuldt, PhD
Assistant Professor, 
Division of Pediatric Rheumatology, Allergy, & Immunology
Department of Pediatrics
University of Minnesota    

Investigators: 

Sara Hamilton Hart, PhD and Nathan Schuldt, PhD

Microbes are an ever present part of normal life that fundamentally shape immune development. Yet, common laboratory animal models limit microbial exposure to reduce the confounding effects of variable microbial experience, resulting in animal models that may not reflect natural immune development or responses faithfully. We investigate the gap between mice that develop under physiological microbial burden and mice raised under conventional specific pathogen free conditions to understand the influence of microbial exposure on immune function. 

A Team Science Approach to Identify the Role of Genetic Ancestry in Ewing Sarcoma Tumorigenesis using Human iPSC Modeling

Speakers: 

Kelsie Becklin, PhD and Rachel Moss    

Investigators: 

Beau Webber, PhD
Associate Professor,
Division of Pediatric Hematology & Oncology
Department of Pediatrics
University of Minnesota

Logan Spector, PhD
Professor & Division Director,
Division of Pediatric Epidemiology & Clinical Research
Department of Pediatrics
University of Minnestoa

Ewing Sarcoma (ES) is a rare but deadly bone tumor, with stagnant survival rates for decades despite knowing the driving oncoprotein, EWS-FLI1. The Spector and Webber labs combine computational, population genetics, and stem cell engineering approaches to understand the etiology of Ewing sarcoma. We have leveraged the disparate incidence of ES between European (EUR) and African (AFR) ancestry to study ES tumorigenesis in iPSC-derived cells from donors with a range of AFR ancestry. We present the results of functional and molecular profiling from our pilot, describing the novel, scalable model of early EWS-FLI1 response and identification of thousands of ancestry-linked changes to gene expression and EWS-FLI1 binding. As EWS-FLI1 itself has proven elusive to direct targeting, studying its immediate downstream effects has the potential for establishing new druggable biologic pathways for treatment of ES.