Research

Current Research

Supinder Bedi, PhD

Instructor of Pediatric Surgery

Division of General and Thoracic Pediatric Surgery

Charles S. Cox, MD

Children's Fund Distinguished Professor
Director of the Pediatric Trauma Program at Children's Memorial Hermann Hospital

Pediatric Traumatic Brain Injury
Traumatic brain injury (TBI) affects nearly 1.5 million patients each year in the U.S. with a cost of nearly 60 billion dollars associated with it. TBI results in long-term physical and cognitive deficits. TBI is a central nervous system (CNS) injury that disrupts the normal interactions between the immune system and CNS. A CNS injury can lead to the production of inflammatory mediators or the disruption of the homeostatic signals in the circuitry of the neural-immune interactions. Immune responses are governed by distant organs such as the spleen and thymus, which act as “bioreactors” when combined with progenitor cell therapy. One potential target of the “bioreactors” is microglia, the resident immune-response cells of the CNS. After injury, microglia (macrophages) differentiate into two different phenotypes. The early phase after injury is dominated by M1 microglia that are considered pro-inflammatory. They potentially release pro-inflammatory cytokines such as IL-1, IL-6 and TNFα. The other microglia (M2) is anti-inflammatory. It releases cytokines such as IL-4 and IL-10. The ratio of M1 vs M2 is potentially a critical factory in a prolonged inflammatory state. We are currently investigating the signaling mechanisms that govern this ratio and the subsequent consequences of the changes in the ratio of M1:M2 when combined with progenitor cell therapy. In addition, we are also examining the role of tissue (Electrospun) scaffolds as carriers for cells intended to treat TBI. Tissue scaffolds provide mechanical, geometric and chemical indicators that promote and modulate cell growth. Electrospinning is a relatively simple method of producing tissue scaffolds with geometries similar to those found in the extracellular matrix (ECM) of living tissue. The process of electrospinning involves the use of an electric field to extrude thin fibers that accumulate to create the scaffold. Electrospun scaffolds have been applied to many different areas of the body including blood vessels, bone, and nerve grafts, and can be used with either natural or synthetic biomaterials. We are attempting to use electrospun scaffolds as carriers for cells intended to treat traumatic brain injury (TBI). This requires studying the fabrication parameters that influences cell growth, and the potential for neuroprotection and neurogeneration following TBI.
Safety of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury in Children
This is a FDA approved pilot study, conducted at Children’s Memorial Hermann Hospital and sponsored in part by TIRR, to determine if bone marrow harvest and transplantation are safe in children with SCI. Ten children, ages 0-15 years of age who have suffered a SCI within 6 months to 4 years of study enrollment, will undergo bone marrow aspiration. Following cell processing, the children will then receive an Intravenous infusion of their cells. They will return at 30 days and 6 months post-procedure for follow-up to assess late functional outcome using pre-transplantation spinal cord function as the control.
Safety of Autologous Human Cord Blood as a Treatment for Traumatic Brain Injury in Children
This is a FDA approved pilot study, conducted at Children’s Memorial Hermann Hospital and sponsored in part by Cord Blood Registry (CBR), to determine if autologous hUCB transplantation for TBI is logistically feasible and safe. Ten children, ages 18 months -17 years who have suffered a severe to moderate TBI 6 months to 18 months prior and who have their own cord blood banked at CBR, will receive an intravenous infusion of their cord blood derived cells. Follow-up will occur at 6 months, 1 year and 2 years post-procedure to assess improvement using pre and post-TBI neuropsychological and imaging outcomes measures.

William I. Douglas, MD

Associate Professor
Chief of the Division of Pediatric Cardiovascular Surgery.

Medtronic – Contegra Pulmonary Valved Conduit for Humanitarian Use
The Contegra device is indicated for patients under the age of 18 for the correction or reconstruction of Right Ventricular Outflow Tract (RVOT) in the following congenital heart malformations: pulmonary stenosis, tetralogy of Fallot, truncus arteriosus, transposition with ventricular septal defect, and pulmonary artresia. In addition, the device is indicated for the replacement of previously implanted but dysfunctional pulmonary homografts or valved conduits.

Stephen Fletcher, DO

Associate Professor
Chief of the Division of Pediatric Neurosurgery

MEDTRONIC NEUROLOGIC TECHNOLOGIES, “Pediatric Clinical Study of the Durepair Dura Regeneration Matrix”, STUDY
TEXAS COMPARATIVE NEURO-ONCOLOGY PROGRAM RESEARCH PROJECT

Lillian S. Kao, MD, MS

Studies on Hyperglycemia in Surgical Infection.
The goal of this NIH-funded grant is to evaluate two different glycemic control regimens on biologic response and clinical outcome in patients with necrotizing soft tissue infections.
Checklists, Patient Safety, and Surgical Complications: Putting Innovation Into Practice
The goal of this study, funded by The University of Texas Clinical Safety and Effectiveness Grants Program, is to evaluate the effectiveness of operative checklists on compliance with evidence-based measures on two surgical services at a county hospital.
Factors Associated with Infectious Complications on ECMO
PI: Lally
This study is funded by the Extracorporeal Life Support Organization (ELSO). The goals of the study are to characterize infectious complications on ECMO, to determine the effect of infectious complications on mortality, and to survey ELSO centers on antibiotic prophylaxis measures for ECMO patients.
Using Wikis to Improve the Dissemination, Evaluation, and Application of Evidence-Based Medicine in Surgical Practice
Co-I: Tsao
This study is funded by The University of Texas Academy of Health Science Education Small Grants Program. The goal of the grant is to perform a pilot randomized trial of the effect of mandatory journal club wiki participation on surgical residents’ critical appraisal skills and skills in identifying and interpreting the evidence for surgical therapies.

Kevin P. Lally, MD

Chairman, Department of Pediatric Surgery
A.G. McNeese, Chair in Pediatric Surgery
Richard Andrassy Distinguished Professor

Necrotizing Enterocolitis Surgical Trial (NEST)
The NEST trial is a multi-center NIH-sponsored study through the Neonatal Research Network. This randomized, controlled trial is designed to determine the neurological status of patients at 18-22 months as the primary outcome after initial laparotomy or intraperitoneal drainage for infants (<1000 grams at birth) with NEC. In addition, the study also evaluates several secondary outcomes including surgical outcomes, nutritional status, grown and development, and biologic tissue studies. Infants are centrally randomized to immediate laparotomy or initial peritoneal drain. Pediatric surgeons have the option of a preference arm for those neonates thought to be only laparotomy candidates. The NEST trial is the largest neonatal surgical trial ever sponsored by the NIH.
Molecular Studies of Tracheal/Esophageal Anomalies and VACTERL (Vertebral, Anal, Cardiac, Tracheal, Esophageal, Renal and Limbs) Association
This study is created to provide a DNA and tissue bank repository devoted to the study of tracheal/esophageal anomalies and VACTERL association. Blood samples from children with tracheal/esophageal anomalies and/or VACTERL association and their parents will be collected and stored and later used to perform molecular studies to characterize the gene defects for these disorders. These samples will then be used to perform linkage studies and other molecular testing that will ultimately help in the identification of the gene responsible for these anomalies.
Molecular Studies in Congenital Diaphragmatic Hernias
Blood samples collected on children with Congenital Diaphragmatic Hernia (CDH) and their parents are collected at Children’s Memorial Hermann and Texas Children’s Hospital to be housed in a DNA and tissue bank repository devoted to the study of CDH. Material collected in these repositories is stored and used to perform molecular studies to identify and characterize chromosomal regions and specific genes that cause CDH. These samples are also used to perform linkage studies and other molecular testing that will ultimately help in the identification of the affected gene/genes.
Advancing Clinical Research in Pediatric Surgery: An Observational Study of Infants with Congenital Diaphragmatic Hernia
This is an international registry dedicated to the study of CDH, designed to prospectively review the outcome of all children with congenital diaphragmatic hernia.
Collection of Neuroblastoma Tissue, Bone Marrowand Blood Samples for Laboratory Correlates
Co-PI:Hayes-Jordan
Tumor samples are collected from one hundred children, ages 0-18 years, at MD Anderson Cancer Center and Children’s Memorial Hermann Hospital to establish the potential efficacy of EGF pathway inhibitors in the treatment of children with recurrent neuroblastoma, and provide further justification for their use in Phase I trials.

Yong Li, MD, PhD

Associate Professor
Children's Program in Regenerative Medicine

Children’s Regenerative Medicine
The project will use various cell sources combined with bioengineering scaffolds to build functional tissues for repair of pediatric defects, such as children’s diaphragmatic hernia
Dedifferentiation and Stem Cell Populations
The project aims to enlarge the stem cell pool without genetic modification as a cell source for regenerative medicine.
Adult Embryonic Potential Stem Cells and Application
Obtain natural embryonic potential stem cells from adult tissue for utilization in tissue engineering and regenerative medicine.
Fibrosis and Prevention Studies
Investigate the mechanism behind the fibrosis process after injuries and diseases, and seek methods for prevention of fibrous scar tissue formation

Stacey Moore-Olufemi, MD

Assistant Professor
Division of General and Thoracic Pediatric Surgery

Clinical Research

Gastroschisis: A Prospective Cohort Outcome Study
This is a prospective study to examine the outcomes of all children with gastroschisis at Children’s’ Memorial Hermann Hospital. Specific outcomes that will be evaluated will include length of stay, time until feedings are tolerated, need for additional surgery, and development of complications such as NEC or central line infections.
Creation of Multicenter Database and Analysis of Outcomes in Neonatal Abdominal Wall Defects
This is a multi-center institutional retrospective study to examine the outcomes of children with abdominal wall defects.
STEP Registry
This is a prospective study to examine the outcomes of children with intestinal failure undergoing a Serial Transverse Enteroplasty (STEP) procedure.
Evaluation of Children's Memorial Hermann Hospital Intestinal Failure Program
This is a prospective study to examine the outcomes of all children with intestinal failure at Children’s’ Memorial Hermann Hospital. Specific outcomes that will be evaluated will include length of stay, effect of multidisciplinary management, liver disease, central line care and nutritional strategies.

Translational Research

Gene Expression & Methylation Profiling in Pediatric Intestinal Failure
This is a retrospective study to examine the patterns of genes expressed in the intestine of children with intestinal failure undergoing surgical procedures at Children’s’ Memorial Hermann Hospital. This study will attempt to identify the differential expression of genes in normal versus diseased intestine, so a potential animal model can be developed to evaluate mechanisms contributing to intestinal failure/short gut syndrome.
Genetic Determinants of Gastroschisis-Related Intestinal Dysfunction: Developmental Intestinal Smooth Muscle Phenotypic Plasticity
This is a prospective study to examine the functional genomics of the intestinal smooth muscle in gastroschisis infants.

Basic Research

Molecular Pathophysiology of Gastroschisis-Related Intestinal Dysfunction (GRID)
This a basic science project using a combination of animal models and cell culture to examine the physiological, functional, biomechanical and molecular mechanisms of GRID.

Scott Olson, PhD

Assistant Professor
Program in Regenerative Medicine

Nitin Tandon, MD

Associate Professor in the Department of Pediatric Surgery
Associate Professor, The Vivian L. Smith Department of Neurosurgery

Brain mapping with functional MRI, electrical stimulation and diffusion tractography
Intra-cranial electrophysiology

Fabio Triolo, PhD

Assistant Professor

Director, cGMP Facilities
Program in Regenerative Medicine

KuoJen Tsao, MD

Assistant Professor
Division of General and Thoracic Pediatric Surgery

The Role of Anti-Reflux Surgery for Gastroesophageal Reflux Disease in Premature Infants with Bronchopulmonary Dysplasia (GERD)
The GERD study evaluates the efficacy of fundoplication in premature infants with GERD and BPD. These infants will be randomized into two groups: medical and surgical therapy. The surgery group will proceed with fundoplication and be re-evaluated at 1 & 2 months. The medical group will continue with medical therapy and re-evaluated at 1 month and proceed to fundoplication if GERD is still present.
Surgical Complications in Pediatric Patients with Mitochandrial Disorders
This study provides an accurate reflection of the outcome of children with mitochondrial disease that have suffered a complication related to surgery at Children’s Memorial Hermann Hospital between January 1, 2000 to May 1, 2010.
Qualitative Analysis: Physicians’ attitude and determinants for the role of anti-reflux surgery for Bronchopulmonary dysplasia in preterm infants with neonatal gastroesophageal reflux disease
This Qualitative Analysis will determine the heterogeneity of physician attitudes in the diagnosis and treatment of neonatal gastroesophageal reflux disease in association with Bronchopulmonary dysplasia in preterm infants.

Karen L. Uray, PhD

Assistant Professor
Division of General and Thoracic Pediatric Surgery

Mechanism of resuscitation-induced ileus: disregulation of MLC phosphorylation.
Intestinal edema development in trauma patients causes decreased intestinal motility, a significant complication leading to delayed enteral feeds, increased septic complications, prolonged hospital stays and a major economic burden. Intestinal edema dramatically impairs intestinal contractility via decreased smooth muscle myosin light chain (MLC) phosphorylation. Preliminary data suggest that while MLCK is unchanged, MLC phosphatase activity is increased in edematous intestinal smooth muscle. Understanding the mechanism by which edema alters the regulation of MLC phosphatase activity is essential in understanding how edema causes intestinal contractile dysfunction in trauma patients. The objective of this study is to understand the molecular mechanisms by which edema alters the regulation of MLC phosphatase. The central hypothesis is that intestinal edema inhibits MLC phosphorylation by abrogating the constitutive inhibition of MLC phosphatase.
Role of NF-kappaB in edema-induced intestinal dysfunction.
Preliminary data suggest that edema induces decreased inhibition of MLC phosphatase resulting in decreased MLC phosphorylation. NF-kappaB activity is significantly upregulated with edema formation and inhibition of NF-κB attenuates edema-induced decreases in MLC phosphorylation and consequently, preserves contractile activity in edematous intestine. We hypothesize that NF-κB activation induces decreased MYPT1 phosphorylation in edematous intestinal smooth muscle. We propose in our model, supported by preliminary data, that in the edematous intestinal smooth muscle, NF-κB induces increased Rnd1 expression which inhibits Rho kinase mediated (inhibitory) phosphorylation of MYPT1 resulting in more MLC phosphatase activity and, thus, decreased MLC phosphorylation.

Pamela Wenzel, PhD

Assistant Professor
Regenerative Medicine

In an effort to identify new ways of improving cellular therapies available for the treatment of pediatric hematopoietic disorders, injuries, and cancers, we pursue two major research areas in the lab. Each are designed to define the role of biomechanical force as a regulator of cellular potential and function, and emphasize the impact of frictional force (shear stress) and stretching (circumferential strain) on genetic programs that determine stem cell specification and self-renewal: (1) in the embryonic blood system and from embryonic stem cells; (2) in adult cells, including mesenchymal stem cells, endothelial cells, cancer cells, and other types of progenitor cells present in the hematopoietic and vascular niches.

Induction of Hematopoiesis
In the developing embryo, initiation of the heartbeat causes blood to circulate through the vasculature and subjects vessel walls to hemodynamic forces, including friction, pressure, and stretching. Recently, we have found that the frictional force (shear stress) created by fluid flow is a powerful, and even necessary, signal for emergence of hematopoietic stem cells and progenitors during embryonic development.
Our current research is designed to address how biomechanical force activates the hematopoietic program and how we might use this information in the laboratory to expand improved sources of hematopoietic cells that can be used for patients in the clinic. A number of candidate genetic and biochemical pathways are currently under investigation as key players mediating this signaling cascade, and we employ various approaches to evaluate their role in blood development, including biomechanics, microfluidics, pharmacology, embryonic stem cell modeling, mouse genetics, and transplantation assays.
Stromal Biology and Regenerative Medicine
Biomechanical force is present throughout the body and impacts a wide array of tissues and cell types. We now know that blood development is intimately linked to the physical forces present in the hematopoietic niche, but these are not the only types of cells sensitive to the unique signaling cascades of mechanical stress. Endothelial cells that line blood vessels are renowned for their sensitivity to fluid shear stress within the vasculature and adapt to changes in blood flow by modification of morphology, gene expression programs, and release of paracrine and endocrine signaling molecules that impact progression of cardiovascular disease and inflammation.
Shear stress also modulates behavioral response of mesenchymal stem cells and other cells of the stroma, and the intensity of mechanical stimulation is known to impact cell cycle (proliferation), anti-apoptotic signaling (survival), and differentiation (fate decisions) of these cells. Our research aims to evaluate the effects of biomechanical force on a number of biological processes, including innate immune response, inflammatory signaling, cellular adhesion, and metastasis. Experiments are designed to utilize culture-based assays, cellular phenotyping, and mesenchymal stem cell-based therapy models of stroke and traumatic brain injury as readouts of response to mechanical stimuli.
Scientific Approaches
Projects rely upon in vitro methodologies for the exposure of stem cells to shear stress and cyclic strain, and we pair this approach with in vivo functional analyses in animal models of blood development and neurological injury. Experiments often require a combination of classical cell and molecular biology techniques, fluorescence activated cell sorting, chemical and mechanical engineering, small molecule screens, large-scale gene expression analysis, and modeling in animal subjects.
More on Wenzel lab studies

Shiraz Ahmad Younas, MD

Assistant Professor
Chief of the Division of Pediatric Orthopedic Surgery

Synthes-VEPTR-Vertical Expandable Prosthetic Titanium Rib for Humanitarian Use
The VEPTR device is a device indicated for the treatment of Thoracic Insufficiency Syndrome (TIS) in skeletally immature patients. This device will be implanted in surgery under general anesthesia during a overnight stay in the hospital. The child will come back to the hospital every 4-6 months to make the device longer until they reach skeletal maturity.