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The mentors in the Program have a long history of mentoring students. Each mentor will spend significant time in the laboratory with the student, mentoring by example and discussion. All of the mentors are active at the bench or in clinical research and will be involved in the education and professional development of student.
Lillian Ambroggio, PhD
The goal of the Ambroggio lab is to improve the health of children through improved diagnostic methods for common serious infections. The specific focus of the lab is to improve the care of children with pneumonia by developing better detection methods for pathogen etiology and more sensitive imaging techniques to detect pneumonia. This will allow clinicians to more accurately prescribe effective pharmacotherapy. These goals are pursued through research in ultrasonography and metabolomics which will permit the identification of candidate biomarkers that can ultimately be translated to the bedside for rapid pathogen identification.
Raouf Amin, MD
Dr. Amin’s research program focuses on 3 areas of investigations in pediatric sleep including upper airway function in children with sleep apnea, mechanisms of resolution of sleep apnea after surgical interventions such as adenotonsillectomy and bariatric surgeries, and the cardiovascular and neurocognitive outcomes of sleep apnea in children. Medical students will receive specific training in the methods of hypothesis-driven clinical research. Studnets will also be exposed to other sleep research projects and receive mentorship on abstract preparation and will be invited to collaborate on manuscripts, as appropriate.
James Bridges, PhD
Dr. Bridges investigates the role of hypoxia inducible factors (HIFs) and downstream gene targets in chronic lung disease. These goals are achieved by utilizing both gain and loss-of-function mouse models to evaluate the mechanistic basis underlying the pathophysiologic changes in pulmonary function associated with altered HIF activity.
Zack Cleveland, PhD
Dr. Cleveland’s research interest is centered on developing magnetic resonance-based imaging techniques to visualize lung structure and function in humans and in small animal models of disease and injury. A particular focus of his research has been on visualizing ventilation and diffusive gas uptake using hyperpolarized (HP) 129Xe MRI. His focus will be to develop novel magnetic resonance imaging methods to assess regional lung function in preclinical animal models, as well as adult and pediatric populations. His emphasis will be directed toward developing techniques to quantitatively image pathophysiology in poorly understood disorders such as acute lung injury (ALI) and idiopathic pulmonary fibrosis.
J.P Clancy, MD
Dr. Clancy’s laboratory and clinical research projects focus primarily on airway epithelial biology, examining restorative strategies to treat cystic fibrosis and to restore protease dysregulation in lung inflammatory disorders. The goals of his research program are 1) to examine strategies to restore activity to mutant, disease-causing CFTR mutations in preclinical model systems and in human subjects, 2) to develop new biomarkers of CFTR activity, and 3) to investigate novel inflammatory pathways contributing to lung injury in acute and chronic pulmonary diseases. Dr. Clancy utilizes these themes to provide research training platforms to future physician-scientists, focusing on translational research across model systems to human subjects.
Todd Florin, MD
Dr. Florin’s research focuses on both epidemiologic studies and well as clinical trials in children evaluated in the emergency room with pneumonia and bronchiolitis. Specifically, he studies the use of clinical prediction modeling and biomarkers to risk stratify children with pneumonia in the emergency department (ED) setting. His research team includes co-investigators and mentors that provide essential expertise in pneumonia, emergency medicine research, epidemiology and the development of clinical prediction models.
Patricia C. Fulkerson, MD, PhD
Dr. Fulkerson’s research program is focused on the biology of the eosinophil lineage-committed progenitor (EoP). The overall aim is to identify novel therapeutic targets to block eosinophil production for the treatment of patients with eosinophilic disorders such as allergic asthma. Tissue eosinophilia is primarily attributed to the influx of mature eosinophils from the circulation, but recent studies suggest that another mechanism may also be at work. EoPs have been identified in increased numbers within allergic mucosa and in sputum from patients with asthma, suggesting eosinophil differentiation in situ may contribute to the accumulation of effector eosinophils in tissues. Potential projects for medical students working in the lab include investigating the contribution of EoPs mobilized from the bone marrow during an allergic response to eosinophil accumulation in the asthmatic lung using experimental models of asthma and innovative culture systems we have developed in the lab.
Daniel Grossoehme, DMin
Dr. Grossoehme’s lab conducts discovery-oriented behavioral/social science of psychological and spiritual factors contributing to treatment adherence, and develops and tests interventions to enhance disease self-management, coping and health-related quality of life. Medical students will share in the on-going efforts of the lab: recruiting participants, conducting Daily Phone Diary interviews, assisting with data entry, and analyzing social network data. They may conduct qualitative interviews, or serve as interventionists in a behavioral trial, depending on timing and interests. Students will receive regular mentoring to successfully complete their project—whether in cystic fibrosis or another pulmonary population--and present their findings by poster and or manuscript.
Theresa Guilbert, MD
Dr. Guilbert is a pediatric pulmonologist performing clinical research focusing on identifying the roles of early life risk factors, exposures, and environment interactions that lead to early childhood asthma and recurrent wheezing. Much of Dr. Guilbert’s research experience has been with multicenter trials and networks. Another area of research interest is using clinical electronic medical data and subsequent linking of this data to public and databases on environmental, socioeconomic, and demographic profiles in order to identify asthma phenotypes. Specific interventions will be targeted to these phenotype populations and clinical outcomes will then be followed in the electronic medical record. Dr. Guilbert utilizes these research interests to provide research training opportunities for future physician-scientists.
William Hardie, MD
Dr. Hardie’s laboratory is primarily focused on examining cell signaling pathways that lead to pulmonary fibrosis and to determine whether pharmacological inhibitors currently in clinical trials are effective in reversing fibrosis or preventing progression. The goal is to generate preclinical data, which may be used to support clinical trials in disorders causing pulmonary fibrosis. Medial students working in the laboratory will participate in both in vivo animal models as well as cell-based model systems testing interventions to prevent or reverse progressing fibrosis. Students will be carefully mentored to develop a hypothesis-driven project and trained in the methodologies needed to address the questions.
Gurjit (Neeru) Hershey MD, PhD
Dr. Hershey’s research centers on identifying the genes and environmental factors important in promoting asthma and allergy, especially at the epithelial surfaces, and dissecting the molecular mechanisms underlying their contributions. Current projects in the laboratory include: (1) Elucidation of epithelial genes and exposures critical to allergic disease; (2) Genomic biomarkers of treatment response in childhood asthma; (3) Gene: environment interactions in asthma and allergic diseases; (4) Mechanistic basis of the adverse effect of traffic pollution exposure in early life; (5) pathogenesis of atopic dermatitis; and (6) Identification of genetic and biologic markers of allergic diseases.
Simon P. Hogan PhD
Dr. Hogan’s laboratory is primarily focused on examining the importance of microRNA (miRNA’s) in the regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) protein expression and function in Cystic fibrosis (CF). The underlying molecular basis of CF is a defect in the CFTR protein, a chloride ion (Cl-) channel that regulates the absorption and secretion of salt and water in various tissues including the lung, sweat glands, pancreas, and gastrointestinal tract. We have recent data demonstrating that miRNA’s, small noncoding RNAs (~22 nucleotides), can modulate CFTR biosynthesis and function in human bronchial epithelial cells. The goal of the research studies is to develop anti-miRNA therapeutics to stimulate CFTR biosynthesis and can successfully recapitulate CFTR function in the majority of CF individuals. Medial students working in the laboratory will participate in both in vivo animal models as well as in vitro human cell-based model systems examining miRNA regulation of CFTR biosynthesis and function in CF.
Tanya Kalin, MD, PhD
Dr. Kalin’s laboratory focuses on the transcriptional regulation of carcinogenesis. We use mouse cancer models to gain insight into regulation of cell signaling pathways required for tumor initiation, progression, metastasis and tumor angiogenesis. The ultimate goal of our research program is to identify novel target genes for diagnosis, prevention and treatment of lung and prostate cancers.
Vladimir Kalinichenko, MD, PhD
Dr. Kalinichenko is interested in transcriptional regulation of epithelial, endothelial and inflammatory cells during lung development and lung injury. The focus is made to Winged helix/Forkhead Box (Fox) proteins FoxM1, FoxF1 and FoxF2 and their role in regulating cell signaling pathways required for cellular proliferation, differentiation, motility and survival, ultimately identifying novel mechanisms that cause human lung malformations and promote lung repair after the injury. Our research led to identification of mutations in FoxF1 gene locus in 30% of patients with Alveolar Capillary Dysplasiawith Misalignment of Pulmonary Veins (ACD/MPV), a developmental disorder with mortality rate of 100% during first several month of life. Currently, we are using various transgenic and knockout mouse models to determine the role of Fox proteins in lung development and various lung diseases, such as ACD, Bronchopulmonary dysplasia (BPD), asthma and lung cancer.
Carolyn Kercsmar MD
Dr. Kercsmar’s current research includes projects examining asthma outcomes, health care delivery strategies, implementation of IT and decision support in asthma care, and molecular phenotyping of acute and chronic asthma. The Cincinnati Children’s Asthma Program is also one of the sites for the Inner City Asthma Consortium and is currently involved in several investigations examining immune mediated interventions for inner city children and adolescents with asthma. Medical students could be involved in projects examining the effectiveness of decision support tools in asthma management, inpatient asthma care, role of cockroach exposure on asthma morbidity, use of text messaging to improve asthma adherence and control, and use of spirometry to improve asthma management in children.
Paul Kingma MD, PhD
Dr. Kingma is a neonatologist and Co-Director of the Fetal Care Center of Cincinnati. His clinical expertise in neonatology includes managing children with congenital diaphragmatic hernias and neonatal infections. Dr. Kingma’s lab investigates the role of the innate immune system in pulmonary infections in children. Specific projects currently focus on the role of surfactant protein D in neonatal sepsis and acute respiratory distress syndrome and on lung injury in congenital diaphragmatic hernia patients. Students will work directly with Dr. Kingma and his associates on any of these projects during their summer tenure.
Tom Korfhagen MD, PhD
SP-A and D are members of the collectin family of innate immune molecules. These proteins are expressed at high levels by the lung epithelium and secreted into the airspace. Current research is focused to determining the mechanisms by which SP-A and SP-D protect the developing and mature lung from inflammatory injury. Experimental approaches employ in vitro studies with macrophages and epithelial cells and in vivo studies using mouse models of SP-A or D deficiency or over production. Additional research builds upon recent work were our lab identified SPDEF as the major inducer of pulmonary Goblet cell metaplasia. Current studies show a protective role of SPDEF against lung inflammation. Research is ongoing to determine mechanisms of SPDEF protection by modifications of signaling through pathogen recognition receptors.
Melinda Butsch Kovacic, PhD, MPH
Dr. Butsch Kovacic’s research focuses on the development of more tailored approaches to prevent and treat chronic disease based on individuals’ known risk factors or measurable biomarkers. In working towards these goals, she melds epidemiologic approaches with innovative laboratory methods. Specifically, her research currently focuses on identifying genetic, environmental and molecular biomarkers of childhood asthma and cancer using human biospecimens and clinical data.
Tim LeCras PhD
The LeCras lab studies the mechanisms that regulate and coordinate lung development, and particularly blood vessel development in the lungs. The lab integrates transgenic mouse models, cell culture studies, and gene arrays to identify new genes and pathways that play a role in newborn lung development, and lung disease in newborns and also children and adults who develop chronic lung diseases and pulmonary hypertension. The long-term goal of these studies is to develop new therapeutic targets for chronic lung diseases, including lung disease in premature infants, pulmonary hypertension, and asthma.
Ian Lewkowich, PhD
Dr. Lewkowich’s laboratory is focused on the immunologic mechanisms responsible for the development of severe allergic asthma. Using a mouse model of allergic asthma in which one strain develops a phenotype characteristic of mild asthma and others develop a phenotype characteristic of severe disease, his group has identified several novel mechanisms through which asthma severity is regulated. Utilizing these mouse models his group is specifically investigating the role of T-cell regulatory immune cells and dendritic cells which influence the inflammatory response to asthmagenic antigens. Students would have the opportunity to work directly using these experimental models of asthma developed in the laboratory.
Satish Madala PhD
Dr. Madala’s research interests are to identify the cellular and molecular mechanisms involved the initiation, maintenance, and progression of pulmonary fibrosis. His lab’s research tools include using molecular, biochemical and immunology methods to identify novel therapeutic targets in chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc), and cystic fibrosis (CF). The lab’s early studies using several mouse models of fibrosis have revealed that multiple growth factors contribute to the deposition of collagen and other extracellular matrix (ECM) proteins in the lung. The lab’s recent studies have helped to define unique functions of fibrocytes and their heterogeneous interactions with other lung stromal cells in causing the expansion of adventitial and pleural fibrotic lesions in the lung.
Frank McCormack, MD
Dr. McCormack is Division Director for adult pulmonary critical care and sleep medicine at the University of Cincinnati. His basic laboratory focus includes examining the pathogenesis of lung disorders including pulmonary Langerhan's cell histiocytosis, pulmonary alveolar microlithiasis, and pulmonary lymphangioleiomyomatosis, rare diseases affecting both children and adults. He is also interested in the role of the pulmonary epithelium in innate immunity, especially as it relates to influenza. In the clinical research realm, he has an active trial program in rare lung diseases.
Louis Muglia, MD, PhD
Dr. Muglia has pioneered the in vivo analyses of regulation of the endocrine stress response and the molecular pathways leading to birth using novel genetically altered mutant mice. These studies have evolved over the last decade to specifically focus on the mechanisms controlling the timing for birth in humans using genetics and comparative genomics. The composition of the biological clock metering the duration of human gestation remains a central question in reproductive biology. The goal of the Muglia laboratory is to understand the molecular timing machinery comprising this biological clock to prevent or better treat human preterm labor.
A.P. Naren, PhD
Dr. Naren's laboratory studies interactions between the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein and its binding partners and defining how spatiotemporal regulation of CFTR-containing macromolecular complexes in the apical compartment of polarized epithelial cells lining the secretory epithelia regulates overall fluid secretion. The long-term goal of this work is to identify new drug targets for cystic fibrosis and other diseases resulting from CFTR dysfunction and provide insights into the etiology of diseases associated with CFTR-interacting molecules.
Anne-Karina Perl, PhD
Dr. Perl lab utilizes conditional transgenic mice to learn about lung development and to study lung regeneration, and more recently, to study aberrant epithelial repair and lung fibrosis. The Perl lab is integrating lessons learned from lung development with lung repair and successfully established novel conditional mouse models to study re-alveolarization and bronchiolar repair after acute and chronic injury. Current research projects are focused toward understanding the cellular and molecular mechanisms related to the cure of lung diseases including bronchopulmonary dysplasia, emphysema, chronic obstructive pulmonary disease (COPD) and bronchiolitis obliterans.
Marc Rothenberg MD, PhD
Dr. Rothenberg’s lab has several areas of concentration. The main objective is to elucidate the processes involved in allergic responses in the gastrointestinal tract and lung using cutting-edge approaches of molecular biology, genetics, biochemistry, translational medicine, and computer computation. The importance of key molecules in the body that perpetuate the allergic responses by examination of genetically induced experimental mouse models are employed. Dr. Rothenberg’s lab characterizes the regulation and pathways responsible for eosinophil development and activation and tests the importance and dysfunction of these pathways in patients with inflammatory diseases such as eosinophilic esophagitis and hypereosinophilic syndromes. A direct clinical project includes identifying genetic variations that may predispose patients to eosinophilic disorders.
Patrick H. Ryan, PhD, MS
Dr. Ryan is an environmental epidemiologist whose research interests include air pollution epidemiology and exposure assessment. Currently he is the principal investigator of the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS), a longitudinal birth cohort study of the effects of diesel exhaust particles on children’s respiratory health and neurodevelopment. His research with the CCAAPS study includes the development of land-use regression models for air pollution exposure assessment and the association between air pollution, respiratory health, and neurobehavioral development. His research also includes the application of novel sensor technology for personal sampling of air pollution, the effectiveness of anti-idling efforts to reduce air pollution exposures at schools, and the use of HEPA filtration to reduce indoor air pollution exposure.
Samir S. Shah, MD, MSCE
Shah is a pediatric infectious diseases and pediatric hospital medicine physician whose research focuses on improving the efficiency and quality of care of children hospitalized with common, serious infections such as pneumonia and asthma. Ongoing projects include studying the comparative effectiveness of different antibiotics in the treatment of community-acquired pneumonia and developing novel databases to conduct comparative effectiveness research in asthma.
John Shannon PhD
Research in Dr. Shannon’s laboratory is focused in two areas. First, Dr. Shannon is investigating the molecular mechanisms regulating the specification and patterning of lung epithelial progenitors from primitive endoderm in the early mouse embryo. This includes identifying new effector genes in this process, then defining their ontogeny, pattern of expression, and function through loss-of-function studies. A summer student could easily be incorporated into these studies. The second area is the functional differentiation of alveolar epithelial cells in the lung, particularly in the area of surfactant phospholipid biosynthesis. Dr. Shannon is currently funded to study LPCAT1, a gene that is critical for making the transition to air breathing at birth. A trainee in Dr. Shannon’s lab would be mentored to develop a hypothesis-driven project related to lung development, then trained in the methodologies needed to address the questions.
Narong Simakajornboon MD
Dr. Simakajornboon researches the correlation between periodic limb movement disorder (PLMD) in children and low iron storage in a larger patient population. The effect of iron therapy on PLMD is prospectively investigated in a double blinded, placebo-controlled approach. All pediatric patients with PLMD at Cincinnati Children's are being recruited into the study. An overnight polysomnographic evaluation is performed in all patients to confirm the presence and severity of disease. Complete blood count, serum levels of iron, total iron-binding capacity, percentage iron saturation and ferritin is obtained in all patients and compared with age and sex-matched control. Patients with low iron storage are randomly assigned to receive treatment with either iron sulfate or placebo. The treatment response will be measured by an improvement in clinical symptoms, actigraphy monitoring and overnight polysomnographic study. Medical students will participate in the recruitment and data analysis of this ongoing project.
Bruce Trapnell MD
Dr. Trapnell has a longstanding interest and effort in translational pulmonary research focused to molecular pathogenesis, diagnosis, and therapeutic development for rare lung diseases including cystic fibrosis, pulmonary alveolar proteinosis, alpha 1 antitrypsin deficiency, lymphangioleiomyomatosis and pediatric interstitial lung diseases. Dr. Trapnell’s basic, clinical, and translational research in animals and humans uses biochemical, physiologic, genetic, bioinformatics and clinical trial approaches.
Brian Varisco MD
Dr. Varisco is in Critical Care Medicine and his laboratory focuses on understanding the role of stretch in regulating postnatal lung morphogenesis. Specific areas of focus are the role of stretch in the transcriptional and non-transcriptional regulation of lung matrix remodeling, the role of matrix remodeling in inducing microvascular expansion, and defining how lung stretch influences epithelial and mesenchymal signaling pathways. The ultimate goal of the Varisco laboratory is to understand how the postnatal lung grows in a ventilation-perfusion matched manner and to leverage this knowledge to develop novel therapies to improve lung health in patients with congenital and acquired disorders of alveolar simplification.
Yui-Hsi Wang PhD
Dr. Wang’s laboratory is investigating the mechanisms that govern the plasticity of tissue resident TH2 memory/effector cells in the airway. Dr. Wang is particularly interested in understanding how the inflammatory mediators, such as IL-1β, IL-33, and IL-25, regulate the development of IL-17-producing TH2 or IL-9-producing TH2 cells during airway allergic inflammation. The long term goal is to explore the roles of acquired inflammatory properties of IL-17-producing TH2 or IL-9-producing TH2 cells in contributing to the heterogeneity and severity of allergic diseases such as asthma.
Tim Weaver PhD
Dr. Weaver’s lab focuses on the molecular pathways that link mutations in the SFTPC gene (encoding surfactant protein C) to development of interstitial lung disease (ILD). Dr. Weaver focused to early molecular events involved in the identification and disposal of terminally misfolded SP-C. The long-term goal of this work is to design reagents that enhance rapid elimination of cytotoxic misfolded proteins. Dr. Weaver has also used transgenic technology to knockin disease-associated alleles into the mouse Sftpc locus. These mice genocopy human patients with ILD and are currently being used to characterize the natural history of the disease, identify biomarkers for diagnosis and prediction of disease progression, and develop novel treatment strategies. Summer medical students would be involved in analyses of these mouse models.
Jeff Whitsett MD
Dr. Whitsett leads a well-established laboratory that has focused its attention to the elucidation of cellular and molecular mechanisms regulating lung formation and function. The laboratory has a long-standing interest in the roles of surfactant proteins SP-A, SP-B, SP-C, SP-D, and GM-CSF in innate host defense and pulmonary function. The mechanisms controlling lung epithelial specific gene transcription are an active area of study, seeking to determine the functions of a number of transcription factors, including the members of the NKX, FOX, SOX, GATA, and ETS families of transcription factors that regulate lung cell differentiation. Genetic pathways mediating lung morphogenesis, maturation, and repair are actively studied, seeking to determine the roles of cell signaling and gene transcription in the pathogenesis of lung disease. The studies seek to understand the molecular pathways causing chronic lung diseases including asthma, cystic fibrosis, emphysema, and lung cancer. The laboratory makes extensive use of conditional, lung specific gene targeting in transgenic mice. Systems biology, with an emphasis on bioinformatics of genomic and expression data, are applied to the study of lung biology. In vivo and in vitro studies are designed to elucidate the cellular and molecular processes regulating lung function. There are many opportunities for the study of both established and novel pathways critical for lung formation and disease pathogenesis within the laboratory.
Kathryn Wikenheiser-Brokamp MD, PhD
Dr. Wikenheiser-Brokamp is a clinical pathologist with research programs in lung development and cancer. Her laboratory studies the genetic and developmental basis of lung disease, with specific interest in the molecular mechanisms controlling epithelial cell growth, differentiation and signaling. Dr. Wikenheiser-Brokamp is specifically interested in mechanisms underlying retinoblastoma (Rb), p16 and p53 tumor suppressor control of epithelial progenitor/stem cell growth and lung carcinogenesis. She also studies the role of Dicer1, and the miRNAs it generates, in lung disease. With mentorship by Dr. Wikenheiser-Brokamp and other laboratory members, the students design controlled experiments, organize and interpret data, and present their findings in oral and/or poster format at laboratory meetings and institutional symposia.
Jason Woods, PhD
Dr. Woods is one of the world’s leading experts on hyperpolarized-gas MRI and the use of such gas MRI to measure regional lung function, microstructure and physiology. Dr. Woods directs the Center for Pulmonary Imaging Research—a multidisciplinary research and training program between Pulmonary Medicine and Radiology. His current ongoing research projects include development of MR-imaging biomarkers to quantify i) alveolar size and morphometry during development and as a result of premature birth, ii) efficacy of treatment after regional or endobronchial interventions, iii) imaging after lung transplantation, and iv) the use of murine models of disease, all ultimately to perform longitudinal monitoring without ionizing radiation in pediatric patients. Possible student projects include studies related to murine lung transplantation, morphometric validation of in-vivo MRI, and quantitative image analysis.
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