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Critical Care Medicine - Research


 

OVERVIEW and FACULTY RESEARCH/ ACADEMIC INTERESTS

Overview

The Section of Critical Care Medicine has a thriving and diverse set of bench, translational, and clinical research programs designed to advance the understanding of and quality of medical care provided to critically ill children.

The Pediatric Critical Care Clinical Research Program supports clinical and translational research projects within the Children’s Hospital Colorado Pediatric Intensive Care Unit. With the contribution of many of the Critical Care faculty as well as investigators from outside the Section, the program provides the infrastructure to execute investigator-initiated and multi-center studies, including feasibility analysis, research management, and mentorship and research training. The program participates in the Virtual PICU System (VPS), a clinical database dedicated to standardized data sharing and benchmarking among pediatric ICUs. Present studies in the PICU include: the role of the airway microbiome in ventilator-associated pneumonia, the impact of Vitamin D in respiratory disease in formerly preterm infants, the association of hyponatremia with outcome in critical illness, and pathophysiology of acute lung injury. The program also participates in multiple multicenter studies including the Genetic Epidemiology of Influenza in Children, Heart and Lung Injury – Pediatric Insulin Titration Trial, and Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care.

The Developmental Lung Biology Laboratory and Cardiovascular Pulmonary (CVP) Research Laboratory at the Anschutz Medical Campus at the University of Colorado Denver represent the backbone of bench research within the Section of Critical Care Medicine. A large multidisciplinary group of investigators from diverse departments within the University including the Departments of Medicine (Pulmonary and Cardiology), Pediatric (Critical Care, Pulmonary, Cardiology, GI) and the Department of Bioengineering work to advance the understanding of the cellular and molecular basis of injury to the developing lung and lung pulmonary circulation, an area of research that is closely related to problems encountered on a daily basis in the PICU.

The research of the CVP includes studies at the basic molecular and cellular levels, as well as translational biology and physiology studies. The laboratory receives substantial funding from the NIH, the American Heart Association, and the American Lung Association.

A program project grant, which is the centerpiece of the Cardiovascular Pulmonary Research Laboratory, comprises four scientific projects focused on studies of the mechanisms of hypoxic pulmonary hypertension (PH). The proposed studies are collectively founded on the hypothesis that the pathogenesis of hypoxic PH involves both functional (vasoconstriction and wall stiffening) and structural (vascular wall thickening) components, and that both components involve hypoxia-induced alterations in resident cell function as well as recruitment and interactions with inflammatory and/or progenitor cells. Four highly collaborative and interactive projects will provide new insights into the cellular/molecular mechanisms of chronic hypoxic pulmonary vasoconstriction and vascular stiffening and remodeling and may lead to novel, more effective therapy for hypoxic PH. The basic work is supported by two major Core facilities. One provides the facilities to expose animals (mice, rats, calves, and humans) to acute and chronic hypobaric hypoxia. In addition, state-of-the-art equipment is provided for hemodynamic assessments of the pulmonary and systemic circulations. A large Cell Culture and Histopathology Core also supports the scientific projects.

In the Developmental Lung Biology Laboratory, which works cooperatively with the Pediatric Heart Lung Center, directed by Dr. Steven Abman, research work is focused on determining mechanisms involved in lung vascular growth. The centerpiece for the laboratory is a Specialized Centers of Clinically Oriented Research (SCCOR) Program. The SCCOR Program generates clinical and basic information that will provide insight into the mechanisms contributing to the pulmonary vascular abnormalities that characterize BPD. This is done by evaluating current available therapies aimed at reducing lung injury and restoring vascular and lung growth and by examining animal models for new approaches to ameliorating perinatal lung injury and restoring vascular and lung growth. Two clinical and two basic projects address these objectives. The clinical projects evaluate (1) the impact of inhaled nitric oxide (iNO) on BPD, and (2) the development of improved techniques to assess the presence of pulmonary hypertension and the responses to therapy in infants with pulmonary hypertension. The two basic projects dissect the mechanisms contributing to lung vascular remodeling in murine, rodent, ovine, and bovine models and evaluate the effects of novel pharmacologic agents on lung vascular disease in these models. Collaborative interactions with National Jewish Health, the Center for Bioengineering, and the Sections of Pulmonology, Neonatology, and Cardiology drive this program forward.

The faculty in the CVP collaborate in a successful training program; weekly seminars and shared resources that all contribute to the exceptional research environment. There are also active collaborations with investigators at National Jewish Hospital, the University of Colorado High Altitude Research Institute. Important new collaborations are also now ongoing on the pathogenesis of ischemic neuronal injury in the immature brain along with researchers in Neurobiology.

Postdoctoral Fellows


Medhi Fini, Hui Zhang, Supervisor: Dr. Stenmark
Leah Villegas, Supervisor: Dr. Grayck

Faculty Research/ Academic Interests


Dr. Joseph Albietz has an academic focus on medical education and clinical informatics, specifically using the evolving technology of the EHR to improve the efficiency and safety of rounding, patient handoffs, and documentation within the ICU environment.  He is the physician lead of the Clinical Application Systems Epic Optimization Team, and is also the co-chair of the Organ Donation Council.

Dr. Robert Dale Brown’s research focus is on inflammatory and fibrotic remodeling of the right heart in cardiopulmonary disease.

Dr. Todd Carpenter's primary research interest is clinical and basic science aspects of acute lung injury in children, including the regulation of lung fluid balance and pulmonary edema formation as well as altitude-related illness in children.

Dr. Angela Czaja's academic interests encompass a range of research areas including epidemiology, health policy and quality improvement. Her current work focuses on off-label medication use in pediatrics, medical decision-making related to medication selection, and national drug policies. She is involved with the PICU quality council at Children’s Hospital Colorado, with a particular interest in unplanned PICU readmissions, and is the physician lead for participation in the VPS national database. Dr. Czaja also is the Associate Director of the Pediatric Critical Care Medicine Fellowship.

Dr. Emily Dobyns is the Medical Director of the PICU, whose main focus is improving patient safety and quality of care delivered to the critically ill pediatric population.  Her specific areas of interest include reducing codes, CA-BSI, and pediatric severity scoring systems (PEWS).

Dr. Jennifer Exo’s primary research interest is in acute neurologic injury and neuroprotective therapies in children. As a member of the Anschutz Medical Campus Neuronal Injury Program, she is studying the effects of cardiac arrest and resuscitation on neuronal death and neurologic outcome in a juvenile mouse model.

Dr. Maria Frid studies the role of bone marrow-derived inflammatory and progenitor cells in pulmonary vascular remodeling. She investigates the mechanisms leading to the recruitment, retention, and differentiation of stem or progenitor cells in the lung and lung circulation.


Dr. Evgenia Gerasimovskaya’s research interests include purinergic signaling pathways in vascular cells, molecular mechanisms of hypoxia-induced ATP (adenosine triphosphate) release, and metabolism of extracellular ATP by ecto-nucleotidases. She also investigates the mechanisms of hypoxic activation of heterotrimeric G proteins, intracellular kinases, as well as Egr-1 transcription factor.

Dr. Eva Grayck is the Director of the Pediatric Critical Care Fellowship Program and has an active laboratory studying the role of reactive oxygen species and antioxidants in the pathogenesis of pediatric pulmonary hypertension. She is interested in the function of reactive oxygen species as signaling molecules that regulate key transcription factors and their downstream targets and in the application of novel antioxidant strategies to treat animal models of BPD and pulmonary hypertension.

Dr. Cameron Gunville is the Medical Director of the Pediatric ICU Midlevel Program, and is responsible for development and oversight of nurse practioner and physician assistant program in the PICU.

Dr. Peter Mourani is the Director of the Pediatric Critical Care Clinical Research Program. He is trained in both pediatric critical care and pulmonary medicine. His research examines mechanisms that contribute to the development of BPD in human preterm infants. He is currently investigating genetic and protein angiogenic factors that may increase susceptibility for BPD and pulmonary hypertension. His investigations of the epidemiology of pulmonary hypertension in BPD include evaluation of echocardiogram measures of pulmonary vascular disease and determination of optimal screening methods for pulmonary hypertension in preterm infants. He is also applying molecular bacterial identification techniques to investigate the role of the airway microbiome to the development of BPD in preterm infants, and to the risk of ventilator-associated pneumonia in mechanically ventilated children in the PICU.

Dr. Carol Okada is the co-director of Education in Pediatrics Across the Continuum at the University of Colorado site, director of a longitudinal pediatric inpatient experience in the Physician Assistant Program at the University of Colorado, and is heavily involved in resident education. She also engages in clinical research involving pharmacokinetics and appropriate medication dosing in obese patients and the care of the critically ill obese patient.

Dr. Kurt Stenmark is the Director of the Developmental Lung Biology Laboratory at UCSOM. As the principal investigator of a Specialized Centers of Clinically Oriented Research (SCCOR) grant from the NIH, Dr. Stenmark leads a group investigating the basic cellular and molecular mechanisms involved in the response of the developing lung vasculature to hypoxia and other injuries, primarily BPD. Dr. Stenmark also directs a program project grant entitled “Adaptations to Hypoxia” in which a large group of investigators examine the molecular mechanisms through which chronic hypoxia elicits changes in the structure and function of lung blood vessels.

Dr. Kathleen Ventre is currently the Director of Simulation Programs at Children’s Hospital Colorado, and maintains an academic focus in developing novel simulation applications and strategies to overcome access barriers to simulation training. She also maintains an academic collaboration with Anesoft® Corporation which has resulted in development of a computer screen-based, interactive PALS simulator in 2006. An updated, web-enabled version of the PALS simulator has been available on the Children’s Hospital Intranet since 2011. Dr. Ventre is a member of the EXPRESS (Examining Pediatric Resuscitation Education using Simulation and Scripting) international research collaborative.

Dr. Carleen Zebuhr’s primary research interest is pediatric cardiac arrest and resuscitation with specific focus on post cardiac arrest and multidisciplinary debriefing using CPR recording devices.