Pediatric Research Newsletter
April 2018
New Chair of Pediatrics Brings His Interest in Acute Care Nephrology and Telehealth Research to Rochester
By Meghan Plog MS
Patrick Brophy MD, MHCDS
Patrick Brophy MD, MHCDS began his tenure as the eighth Chair of the Department of Pediatrics and Physician-in Chief of Golisano Children’s Hospital on January 1, 2018. He came to Rochester from the University of Iowa where he served as the Jean E. Robillard, MD Chair in Pediatric Nephrology, Professor of Pediatrics in the Carver College of Medicine, Assistant Vice President of eHealth and Innovation, Vice Chair of Clinical Innovation for the Department of Pediatrics, and Co-Director of the Integrated Special Populations Research Core in the University of Rochester Clinical & Translational Science Institute. Dr. Brophy has a diverse research portfolio with basic, clinical, health care delivery, and translational interests all falling under the umbrella of, what has been termed, “lifespan research.” That is, looking at how actions taken early in life can impact development and health down the line, as well as reduce cost of care.
A pediatric nephrologist by training with a clinical interest in critical care nephrology in the NICU setting, Dr. Brophy’s basic and clinical research focuses on renal development, with specific interest in acute kidney injury (AKI). His longstanding research in the area of AKI has involved multiple national and international consortia, including ppCRRT and ppAKI, as well as translational studies through the REPaIReD trial, a national investigation looking at proteomic AKI biomarkers in neonatal patients. Currently in the analysis stage, it will be one of the largest analytics studies completed to date. Dr. Brophy is also part of an international collaborative genetics network, which brings together physicians from around the world to coordinate mutational analysis research in selected disorders of the genitourinary tract, including bilateral renal agenesis (formerly Potter syndrome). Dr. Brophy is looking to expand this network, and in doing so, work closely with UR Medicine’s Maternal-Fetal Medicine group. One of Dr. Brophy’s most recent research findings is the identification of gene mutations in “GREB1L” (in the Vitamin A pathway), responsible for renal agenesis. While it is still under investigation, they have developed animal models in fish, frogs, and mice to uncover if levels of Vitamin A may be modulated to improve kidney development. If confirmed, recommendations may be made to ensure appropriate amounts of Vitamin A are being consumed prenatally, much like the current recommendations for folate to protect against neural tube defects. Working with collaborators across the country, he is continuing to explore this effect.
Dr. Brophy also has significant interests in telehealth research. While in Iowa, he founded the Signal Center for Health Innovation, which utilized digital healthcare solutions, including telemedicine, to improve care across the state. Their digital healthcare research spanned from improving provider and patient communication through mobile device technology and videoconferencing, to wearable health technology used to collect sensor data to better understand the spread of hospital acquired infections. Their research and innovations resulted in virtual urgent care and hospitalist services, virtual emergency department and NICU consults, a telestroke program, and mobile device technology to track diabetes in pregnancy, to name a few. He looks forward to collaborating with individuals at the University of Rochester, including at the medical center and the University of Rochester Clinical & Translational Science Institute, to continue exploring new technologies to improve healthcare delivery in at-risk populations, including access to care, in a cost effective fashion.
Pediatric Allergist Funded for Two Major Studies on Immune System Development and Food Allergy
By Meghan Plog MS
Kirsi Järvinen-Seppo, MD, PhD
The prevalence of allergies in children has steadily increased throughout the years, with 6-8% of children in the United Sates currently being impacted. Kirsi Järvinen-Seppo, MD, PhD, associate professor and Division Chief of Pediatric Allergy/Immunology, has dedicated much of her career to studying the early development of infant’s immune system, specifically looking at how immunologic factors in breast milk may impact the development of food allergies in children. Dr. Järvinen-Seppo’s research aims to uncover what predispositions to allergic or infectious diseases may exist in the early months of an infant’s life, and she has recently received two significant grants to carry out this work.
A $2.4 million grant from the NIH is supporting her study comparing infant immune system development in Old Order Mennonites, a community with very low incidence of allergies and asthma, to infants in the greater Rochester area who have high risk for allergy due to hereditary factors (i.e. born to families with a parent or sibling with allergic diseases). Around 1 percent of Old Order Mennonites have food allergies, which researchers believe can be attributed to significant lifestyle factors. Dr. Järvinen-Seppo, in collaboration with several other investigators at the University of Rochester, as well as at the University of Alabama and the Icahn School of Medicine at Mount Sinai, will be studying mother-infant pairs from both communities for the first two years of the child’s life. In addition to visits and questionnaires focusing on lifestyle elements and development of allergic symptoms, they will be collecting biological samples including breast milk, blood samples from mother and child, stool samples for microbiome analysis, skin swabs and nasal swabs. These samples will give them information about the immune system, as well as about the development of microbial species present. The goal is to gather enough information to understand if the immune system deviates early in life, and to identify what lifestyle factors may be responsible for this effect. In the future, interventions aimed at reducing allergy and asthma rates in children may incorporate some of these lifestyle factors from the Old Order Mennonite community that protect against allergic diseases. Dr. Järvinen-Seppo’s group is currently in the enrollment stage of the study, aiming to enroll 80 mother-infant pairs from each group.
A second study, funded by the Bill & Melinda Gates Foundation, is a one-year pilot grant that is attempting to identify antibody profiles to key respiratory and diarrheal pathogens between different geographic locations. Dr. Järvinen-Seppo will be looking specifically at breast milk samples from 6 different cohorts, including the US, Finland, Bangladesh, Peru, and Pakistan. The ultimate goal is to understand whether breast milk antibodies can protect against key diarrheal and respiratory pathogens, which cause significant infant morbidity and mortality in developing countries, and to ultimately identify interventions to boost breast milk immune composition. This is a multi-site project in which URMC is serving as the coordinating center, and this pilot study is part of a larger program at the Gates Foundation assessing the protective properties on human milk. The other centers include Toronto Hospital for Sick Children, University of Virginia, Emory University, and Johns Hopkins University.
Research Publication Highlights
Nov. 2018 - Apr. 2018
- Dr. Laurie Steiner's lab studies epigenetic mechanisms controlling erythrocyte differentiation. Their recent publication in Cell Reports describes a critical role for the histone methylase Setd8 in RBC maturation.
» The Methyltransferase Setd8 Is Essential for Erythroblast Survival and Maturation. - Dr. Jill Cholette was involved in a study showing low Oxidation Reduction Potential, as a measure of oxidative stress, in pediatric cardiopulmonary bypass patients can predict post-surgical complications.
» Oxidation Reduction Potential (ORP) is Predictive of Complications Following Pediatric Cardiac Surgery. - The laboratories of Drs. Fabeha Fazal and Arshad Rahman report that molecules required for intracellular nucleocytoplasmic molecule transport can control tissue inflammation by regulating endothelial cell barrier function.
» Importins α and β signaling mediates endothelial cell inflammation and barrier disruption. - Recent work from Dr. Jill Halterman and her team, showed the significant benefits of telemedicine at school in asthma management.
» Effect of the School-Based Telemedicine Enhanced Asthma Management (SB-TEAM) Program on Asthma Morbidity: A Randomized Clinical Trial. - Drs. Jim Palis and Kathleen McGrath published a set of articles describing their state-of-the-art protocols for studying hematopoiesis.
» Analysis of Erythropoiesis Using Imaging Flow Cytometry.
» Functional Analysis of Erythroid Progenitors by Colony-Forming Assays.