Richard Falcone Jr., MD, MPH
Pediatric trauma research continues to focus on the triage of pediatric trauma patients within the trauma system, and at the level of the pediatric trauma hospital. This work is funded, for two consecutive years, by the Ohio Department of Public Safety. At the system level, this work has allowed an improved understanding of state wide under-triage of injured children, and is now focusing on a better understanding of the triage of pediatric traumatic brain injuries patients throughout the state trauma system. Extensive work by our group has also explored the appropriate triage of injured children on arrival to the pediatric trauma center based on pre-hospital information. As an expansion of this work, Cincinnati Children’s is part of an important R24 funding proposal to further understand EMS triage of children, and how this interacts with trauma center triage. In addition to this important work, the group has published groundbreaking research on how adult trauma centers can significantly improve their care of injured children by partnering with a pediatric trauma center. Finally, our injury prevention work continues to explore the impact of our home safety program and our national Buckle Up for Life program on reducing pediatric injuries. This important work receives funding from Kohl’s Cares for Kids, Messer Construction Company and Toyota.Michael Helmrath, MD
Dr. Helmrath is the surgical director of the Intestinal Rehabilitation Center. His laboratory’s basic and clinical studies focus on evaluating the adaptive response of the bowel to injury and loss. Specifically, the laboratory focuses on the role of intestinal stem cells in small intestinal physiology. His work has been continuously funded by multiple NIH awards. His U01 award aims to lead to a deeper understanding of regional influence within intestinal stem cell populations that may contribute to physiological and disease specific difference commonly seen between the proximal and distal intestine. As part of the Intestinal Stem Cell Consortium (ISCC, NIH), he is actively involved in the intestinal stem cell field. His long-term research goal is to establish translational therapies for the management of patients with short bowel syndrome.Thomas Inge, MD, PhD
Dr. Thomas Inge is a full-time attending physician in the Division of Pediatric General and Thoracic Surgery, the director of the Surgical Weight Loss Program for Teens, and is also the co-director of the Center for Bariatric Research and Innovation (CBRI). He has extensive clinical expertise in medical and surgical management of patients with severe obesity. The main focus of his research is the outcomes of bariatric surgery, for which he has funding from the National Health Institutes (NIH) continuously since 2005. He is the principal investigator of the multicenter Teen-LABS study which was recently awarded five additional years of funding (2017-2022) by the National Institute of Diabetes and Digestive and Kidney Diseases. The CBRI is currently partnering with Cincinnati Children's divisions and other institutions to study the changes in patients after bariatric surgery. Dr. Inge collaborated with other leading Cincinnati Children's physicians and investigators to create the Pediatric Diabetes and Obesity Center (PDOC) with an Academic and Research Committee award from the Children's Cancer Research Fund (CCRF). A PDOC research study is currently recruiting and enrolling participants to address the role of the immune system in the development and progression of obesity and obesity-associated sequelae.Helen Jones, PhD
Helen Jones, PhD, and her lab members investigate the maternal-fetal interface in a broad range of pathologies, and are developing targeted gene therapy protocols to use during pregnancy to improve placental function and fetal growth. With collaborators from the University of Cincinnati, they have developed, and demonstrated, successful, cell-specific gene expression both in primary human trophoblast cultures and a mouse model of placental insufficiency, along with maintenance of normal fetal growth in the mouse model upon treatment. Current studies are underway into the inclusion of targeting peptides onto the nanoparticles for systemic delivery and incorporation of MiRNA seed sequences to address off-target effects.
In collaboration with James Cnota, MD, and the Heart Institute, the Jones lab has demonstrated significant alteration of placental vascular and villous development in cases of congenital heart defects, including hypoplastic left heart syndrome (HLHS),and transposition of the great arteries in humans. They have demonstrated a new mouse model of HLHS recapitulates the human placental phenotype, and will use this to investigate the heart-placenta axis throughout gestation.
Dr. Jones and her team have also established new collaborations with Dr. Kasper Hoebe, PhD, the Division of Immunobiology, to study the role of maternal immune modulation of placental invasion; and Dr. Gruschen Veldtman, FRCP, MBChB, director of Adult Congenital Heart Disease, to investigate placentation in mothers with heart diseases. Dr. Jones has maintained collaborations with Dr. Laura Woollett, UC Pathology, to study the effects of cholesterol on placental development and function,as well as collaborations with Drs. Louis Muglia, MD, PhD, and Michaela Pavlicev, PhD, Center for Prevention of Preterm Birth, to investigate placental involvement in preterm birth.
Maxime M. Mahe, PhD
Dr. Maxime Mahe is an instructor in the Division of Pediatric General and Thoracic Surgery. His research goals are to study human enteric nervous system regulation of intestinal growth and its impact on gastrointestinal dysfunctions. Dr. Maxime Mahe studies the molecular and cellular mechanisms underlying the effects of the enteric nervous system on intestinal epithelial functions using integrated human gut models derived from pluripotent stem cells. The overall goal of his research is to provide insight into the gastrointestinal pathophysiology relevant to congenital dysmotilities, gastrointestinal infections, irritable bowel syndrome (IBS), and Hirschsprung disease. Additionally, Dr. Mahe received the Athena Troxell Blackburn Research Scholar Award from the American Gastroenterology Association.Jaimie Nathan, MD
Jaimie Nathan, MD, surgical director of the Intestinal Transplant Program, and his team are investigating the role of intestinal microbiota in intestinal transplantation and in progression of chronic liver diseases. With grant funding from the American Society of Transplant Surgeons, the team is studying the role of intestinal microbiota in acute rejection after intestinal transplantation with the goal of identifying novel non-invasive biomarkers to predict the development of rejection. Investigating the role that changes in intestinal microbiota play in the progression of chronic liver disease and its complications, and in the development of post-liver transplantation complications in children is the focus of another study funded by the Markham Family Award on Liver Diseases/Liver Transplantation.Jose L. Peiro, MD, PhD
A research team led by Jose L. Peiro, MD, PhD, director of Endoscopic Fetal Surgery at the Cincinnati Fetal Care Center, is continuing investigating the basic mechanisms of pediatric and fetal surgical congenital malformations, focusing especially upon fetal myelomeningocele (MMC), congenital diaphragmatic hernia (CDH), and gastroschisis.
New Trends in Spina Bifida and Neural Tube Defects
Improving the fetoscopic approach for intrauterine repair by evaluating different patches and sealants in animal models (in collaboration with biomedical engineers at the University of Cincinnati, Professor Chia-Ying Lin's Laboratory, and then translating these techniques for use in the human fetus is the focus in MMC. A new clinical trial will compare fetoscopic MMC repair in humans against the standardized open fetal surgery approach.
They are determining the mechanistic processes and pathways activated in the neuro-inflammation and neurodegeneration that appear in open neural tube defects in rodent models. The team is also studying ways to use neural progenitor cells collected from the amniotic fluid of MMC patients as a potential form of neural regeneration (cell therapy).
In collaboration with Dr. Shaaban’s lab, they are using a mouse model of neural tube defects to investigate how maternal immune status can influence incidence of congenital malformations.
Evaluating Fetal Surgery to Support Lung Development
In CDH, they will continue studies in animal models that indicate that early fetal tracheal occlusion may induce faster and better fetal lung growth. A new animal model of CHAOS ligation of the fetal trachea early in gestation perfectly resembles the human histology of this condition. They described comparison of a novel CDH surgically induced model in rats with gene-expression to the teratogen nitrofen-induced CDH model in a collaborative study with Dr. Jeffrey Whitsett’s research group. Also, an excessive reversal of epidermal growth factor receptor and ephrin signaling has discovered the following tracheal occlusion in a rabbit model of congenital diaphragmatic hernia.
They started this year with fetoscopic tracheal occlusion in human fetuses with severe CDH by detachable balloon insertion. This work will contribute to the ongoing multicenter TOTAL trial.
Neuroenteric and Lymphatic Disorders Related to Gastroschisis
In gastroschisis, they are analyzing the neurodegenerative and lymphatic anomalies that associates with fetal gastroschisis and their relation with intestinal hypomotility and malabsorption in the fetal rabbit model.
They are also studying the origin and presence of intrauterine growth restriction in these fetuses with gastroschisis, in collaboration with Dr. Habli and Dr. Helen Jones’ Lab.
Aimen Shaaban, MD
Immunologic Tolerance to In Utero Hematopoietic
Cell transplantation Aimen F Shaaban, MD, is the director for the Center for Fetal Cellular and Molecular Therapy. Research focuses on in utero hematopoietic cell transplantation (IUHCT) for the treatment of congenital diseases such as sickle cell disease and thalassemia with the goal of understanding the steps necessary for successful engraftment and long-term tolerance induction. In a small-animal model, the team is defining the manner in which the fetal immune system first learns to differentiate self from foreign cells. Over the past year, these studies have resulted in publications in the Journal of Immunology and Scientific Reports, as well as research presentations at the American Society of Hematology. Our research program is funded by support from the National Institutes of Health (NIH), and the Children’s Hospital Research Foundation.
Additionally, maintained productive collaborations with: 1) Dr. Sing Sing Way from the Division of Infectious Diseases in probing how fetal exposure to mother’s cells affects future reproductive fitness; 2) Dr. Helen Jones in exploring how the cross-talk between the maternal and fetal immune system affects placental development; 3) Drs. Foong-Yen Lim from the Cincinnati Fetal Care Center; Jose Luis Peiro from the Division of Pediatric General and Thoracic Surgery; and Beth Kline-Fath from the Department of Radiology in the study of how the human fetal lung grows in cases of congenital diaphragmatic hernia; 4) Dr. Kasper Hoebe from the Division of Immunobiology in exploring the mechanisms underlying fetal NK cell development; and 5) Dr. Damien Reynaud from the Division of Experimental Hematology and Cancer Biology in exploring the mechanisms controlling cell-fate decisions in the hematopoietic system. These collaborative works were published in Chimerism, Prenatal Diagnosis, and the Journal of Pediatric Surgery.
