Mentors and Research Areas
Mentors for the Morris Green Scholars Program are successful researchers from throughout the Department of Pediatrics and provide not only research mentorship, but are excellent role models for pediatric physician scientists. Current research areas for Morris Green Scholars Program mentors include:
Morris Green scholars may do research with any investigator from the Department of Pediatrics. Guidance is provided to identify the best mentor for each MG Scholar based on his/her interests and experience.
Mentor Bios
Adolescent Health
J. Dennis Fortenberry, MD, MS – Adolescent Medicine
Dr. Fortenberry is a Professor of Pediatrics and has guided a research program focused on adolescents over the past 15 years. Dr. Fortenberry's research addresses the contextual and interpersonal factors associated with adolescent sexual activity, including the importance of partners as sources of social support for adolescents' care-seeking, stigma and low health literacy as barriers to appropriate health care, and substance use relating to event-specific condom use.
Mary Ott, MD – Adolescent Medicine
Dr. Ott's research examines adolescent health and development with a focus on sexual behavior, unintended pregnancy and sexually transmitted infections (STIs). Dr. Ott's interdisciplinary research program advances our understanding of how development, relationships and social contexts influence adolescent abstinence decisions. Four linked studies use a mix of qualitative and quantitative research methods that are drawn from psychology, sociology, anthropology, and medicine. Her research findings have been translated into practice on several levels: (1) a developmental framework for office-based counseling; (2) evaluation and improvement of Indiana RESPECT, an abstinence-focused public health education program; and (3) research findings have been directly incorporated into Society for Adolescent Medicine policy statements. Dr. Ott's current research is a developmental examination of how adolescent boys' make decisions about romantic and sexual relationships, and the impact of those decisions on STIs. Results suggest important roles for families in STI prevention, and identify patterns of communication that can inform both office-based STD prevention counseling and STD prevention programs.
Sarah Wiehe, MD, MPH
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Angiogenesis
Laura Haneline, MD
David Ingram, Jr, MD
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Asthma & Allergic Diseases
Mark H. Kaplan, PhD - Pulmonary Inflammation and Asthma Research Group
One area of Dr. Kaplan's research is focused on studying the immunobiology of STAT proteins. STAT (Signal Transducer and Activator of Transcription) proteins are a class of molecules involved in signaling from the cytokine receptor directly to the nucleus, where they bind DNA and alter gene transcription. Mice are used that are deficient in Stat3, Stat4 or Stat6, factors involved in signaling for IL-6/IL-23, IL-12 and IL-4, respectively. They have shown that STAT proteins perform non-redundant and crucial roles in cytokine signaling. Current experiments address the questions of how these cytokines promote specific T helper cell effector functions, and how STAT proteins regulate changes in gene expression.
A second interest in the lab is in the pathogenesis of allergic disease. Using mice that express an active Stat6 in T cells, Dr. Kaplan's lab has developed a model for spontaneous allergic inflammation, particularly in the skin, as a model of atopic dermatitis. We are analyzing the cellular and genetic components that contribute to the development of this inflammation. In parallel, we are analyzing the immune profile of infants with atopic dermatitis to determine if there are factors that predict the subsequent development of allergic disease and examine the progression of T cell responses in allergen-sensitized infants.
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Blood Cell Development
D. Wade Clapp, MD – Pediatric Developmental Immunology/Hematology Research Group
Dr. Clapp's laboratory is focused on understanding the molecular pathogenesis of two genetic diseases that result in both hematopoietic malignancies as well as solid tumors. One major area of interest is to understand the role of the NF1 tumor suppressor gene. NF1 is associated with a predisposition to neural crest derived tumors and juvenile myelomonocytic leukemia. Dr. Clapp's laboratory provided the first genetic evidence that haploinsufficiency of NF1 alters cell fates in lineages implicated in the disease pathogenesis of neurofibromatosis type 1. He and his collaborators have demonstrated a key role for the hematopoietic system and the c-kit/kit ligand pathway in plexiform neurofibroma tumor progression, which has led to a phase 2 clinical trial currently underway. Dr. Clapp's group is also interested in the heterogenetic disorder Fanconi Anemia. They are focusing on understanding the molecular mechanisms that underlie the genesis of the bone marrow failure and clonal evolution of hematopoietic malignancies. A third area of emphasis is in the development of gene transfer and transplantation protocols. Dr. Clapp and his collaborators are currently developing modified foamyviral and lentiviral vector delivery systems that appear to have several advantages over traditional retroviruses.
Laura S Haneline, MD – Developmental Immunology/Hematology Research Group
Dr. Haneline's lab focuses on two main areas of investigation. The first are basic studies to understand the pathogenesis of bone marrow failure and leukemogenesis in the genetic disease Fanconi anemia (FA). FA is a complex, autosomal recessive disorder characterized by chromosomal instability, bone marrow (BM) failure, increased incidence of malignancies, and hypersensitivity to multiple classes of DNA damaging agents. The overall goals are to determine the mechanisms by which FA proteins affect multiple complex intracellular processes, which may lead to novel treatment strategies that could potentially delay onset of BM failure and/or malignancy. They are currently evaluating the biochemical and molecular mechanisms responsible for enhanced oxidant sensitivity in FA in order to elucidate potential molecular targeted therapies. The second area of investigation in the lab is based on the observation that infants born to mothers with diabetes during pregnancy have an increased risk to develop hypertension in childhood and adulthood. They hypothesize that a fetus exposed to a diabetic intrauterine environment develops structural and functional changes in the vascular system, specifically endothelial progenitor cells. Future studies to explore the molecular mechanisms responsible for this phenotype are planned using human and rodent model systems.
David A Ingram, Jr, MD – Developmental Immunology/Hematology Research Group
Dr. Ingram's research program focuses on two broad areas. First, he has identified a novel hierarchy of endothelial colony forming cells (ECFCs) utilizing human peripheral blood and umbilical cord blood. In contrast to previously purported endothelial progenitor cell (EPCs), he demonstrated in human genetic studies the EPCs are actually hematopoietic derived macrophages. He also provided several lines of evidence that ECFCs form blood vessels de novo when transplanted in xenograft models. Recently, his laboratory has developed a novel poly-chromatic flow cytometry based assay to identify rare circulating angiogenic cells, which serve as novel biomarkers in patients with cancer and cardiovascular disease. Second, Dr. Ingram's lab has developed several genetically engineered mouse models of cardiovascular disease, which occur in patients with neurofibromatosis type I (NF1). Utilizing lines of cre transgenic mice, he is currently dissecting the molecular mechanisms of the vascular disease in NF1 patients and identifying molecular targets for potential treatment.
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Cancer Biology/Pediatric Oncology
Helmut Hanenberg, MD, PhD
Dr. Hanenberg studies genetic disorders, including their basic molecular biology and phenotypical consequences and the potential for translation to novel clinical therapies. Specifically, he focuses on the molecular identification and clinical characterization of the DNA repair disorder, and the development of novel therapies for inherited and acquired hematological diseases.
Mark R Kelley, PhD – Pediatric Hematology/Oncology Research Group
Dr. Kelley's laboratory studies DNA repair genes involved in repairing base damage that occurs from oxidative and alkylation events in normal and tumor cells and following cancer treatments. His ongoing projects include: (1) Studying the multifunctional Ape1/Ref-1 protein structure/function in order to determine its redox and repair functions in normal cancer cells; (2) Molecular targeted therapeutic approaches at members of the DNA base excision repair (BER) pathway; (3) Role of mitochondrial DNA repair systems in normal and cancer cells; (4) Altering Ape1's redox function and role in angiogenesis as a therapeutic approach for cancer and other indications; (5) Role of DNA repair genes in cognitive dysfunction (“chemobrain”) and peripheral neuropathy; and (6) Analyses of DNA repair genes and their relationship to chemoprevention, cancer initiation, progression and response to treatments.
Jamie L. Renbarger, MD, MS – Individualized Pharmacotherapy in the Treatment of Childhood Cancers
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Cardiac & Vascular Biology
R Mark Payne, MD – Riley Heart Research Center
Dr. Payne's lab is focused on understanding the role of mitochondrial function in heart diseases of children and young adults. Because mitochondria produce virtually all of the energy supply in tissues with high energy demands, such as the heart, they play an essential role in cardiomyocyte survival and function. One area of research in the Payne laboratory is to understand the role of protein targeting and import into mitochondria in order to design genetic therapies to repair or protect mitochondrial function in the heart. Work is underway to develop a novel therapy to replace a missing mitochondrial protein that causes Friedreich's Ataxia, a disease of children and young adults. This is a disease of the heart and nervous system in which the mitochondrial protein, frataxin, is missing. Multiple genetic models of Friedreich's Ataxia and a wide variety of molecular biology techniques are used to test hypotheses of mechanism and therapy in this disease. The long term goal of this work is to develop a new therapy for children with mitochondrial diseases.
Simon J Conway, PhD – Cardiac Developmental Biology Research Group
Research in his laboratory has a common aim - to understand congenital heart defects and prevent in utero lethality. Congenital heart defects are the #1 birth anomaly. Dr. Conway's lab focuses on the pathogenesis of embryonic conotruncal and valvular heart defects, which result from a failure of the aorta and pulmonary trunks to become separate blood vessels and associated outflow tract endocardial cushion/valvular remodeling anomalies. Lack of outflow tract septation often results in lethality secondary to respiratory failure as there is inappropriate mixing of the oxygenated and de-oxygenated circulations postnatally. Similarly, valvular insufficiency can also result in postnatal lethality due to an inability to maintain a unidirectional blood flow and progression of viable latent valve disease. Using both transgenic over-expressor and targeted systemic and Cre/loxP conditional knockout mice models, we are investigating when cardiovascular development first goes wrong in utero, identifying the cell lineages responsible, genetically ablating them using diphtheria toxin-A and then attempting to correct the various heart malformations. If these congenital cardiovascular defects can be prevented and/or nullified in genetically-defined mouse mutant models - they hope to apply the knowledge gained to help engineer potential treatments for pediatric patients. Opportunities are available to analyze transgenic and knockout mice at both the whole animal and molecular levels. Projects are tailored to applicants' experience and interests.
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Diabetes
Raghu Mirmira, MD, PhD - Pediatric Diabetes Research Group
The pathophysiology of diabetes is complex, but it is clear that defects at the level of the insulin-producing islets underlie the development of the disorder in nearly all forms of diabetes. Dr. Mirmira's laboratory focuses on the regulation of gene transcription during pancreatic islet development, function, and survival. The projects in his laboratory fall into three main categories: 1) the role of homeodomain transcription factors, basic helix-loop-helix transcription factors, and PPAR-gamma during the development of islets, and the pathogenesis of islet dysfunction in type 1 and type 2 diabetes, 2) the interrelationships between chromatin structure and gene transcription in the mature islet 3) the role of post-transcriptional mechanisms in cytokine-mediated islet dysfunction. Dr. Mirmira's lab believes that intervening at any of these three stages in the islet life-cycle (development, function, and survival) will allow for the development of new sources of islets for the treatment of diabetes. This translational research includes: A) bench and bedside testing of new inhibitors of the islet inflammatory intermediates (including 12-lipoxygenase, lisofylline, and eukaryotic translation initiation factor 5A), and B) proteomics-based approaches to discover biomarkers to identify or predict the occurrence of microvascular complications of diabetes.
Mark Rigby, MD, PhD
Dr. Rigby primarily studies the immunopathogenesis and prevention of Type 1 diabetes mellitus. Dr. Rigby’s investigations span from studies in animal models and islet transplantation to human investigations. Dr. Rigby works to understand how drugs that prevent disease dampen the effect of harmful disease-causing cells, while encouraging the growth of protective, regulatory cells and the immune barriers in islet transplantation in murine models of diabetes. In addition, Dr. Rigby assists in the evaluation of patients receiving islet transplants for Type 1 diabetes to better understand the immune response in human islet transplantation.
Linda DiMeglio, MD, MPH
Her primary research interest in the field of pediatric diabetes is related to outcomes of children using insulin pump therapy, although she is involved in projects related to cardiovascular outcomes of persons with diabetes.
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Epidemiology & Public Health
Gilbert Liu, MD, MS – Children's Health Services Research
Dr. Liu is an Assistant Professor of Pediatrics and Affiliate Scientist of the Regenstrief Institute. Dr. Liu's research interests include obesity prevention, environmental health, spatial analysis, and medical educational methods.
Sarah Wiehe, MD, MPH – Children's Health Services Research
Sarah Wiehe, MD, MPH is a pediatrician and public health researcher in the section of Children's Health Services Research at Indiana University School of Medicine, an Affiliated Scientist at the Regenstrief Institute for Health Care, and Adjunct Assistant Professor of Geography and Public Health. Her research focuses on how poverty and associated social determinants of health influence adolescent behaviors such as smoking, substance abuse, and risky sexual activity. She is currently studying contextual correlates of sexually transmitted infections using the Regenstrief Medical Record System data and collecting geospatial data. As a Robert Wood Johnson Foundation Physician Faculty Scholar, she is tracking the locations of young women using GPS-enabled cell phones and assessing how their paths are different based on their health-risk behavior choices. Using qualitative and visual sociological techniques, she will develop a set of contextual characteristics potentially pertinent to adolescent health-risk choices.
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Health Policy
Aaron E Carroll, MD, MS – Children's Health Services Research
Dr. Aaron E. Carroll is the Associate Director for Research, an Associate Professor of Pediatrics in the Children's Health Services Research Program at the Indiana University School of Medicine, and the Director of the Center for Health Policy and Professionalism Research. Dr. Carroll's current research interests include the use of information technology in pediatric health care, decision analysis and cost-effectiveness analysis, and health policy and professionalism.
Nancy Swigonski, MD, MPH
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Health Services
Aaron E Carroll, MD, MS – Children's Health Services Research
Stephen M Downs, MD, MS – Children's Health Services Research
Maria Finnell, MD – Children's Health Services Research
Maria Finnell, MD is an Assistant Professor of Pediatrics in Children's Health Services Research. Dr. Finnell's research interests are computer-based decision analysis and quality of life measurements. She has applied decision analysis for recommendations around pediatric latent TB treatment, and is currently working on projects regarding pediatric urinary tract infection guidelines. She is pursuing a Master's in Clinical Science. Dr. Finnell also works in the International Adoption Clinic at Riley Hospital, where she is a pediatric faculty member within the Pediatric Infectious Disease Division at Riley.
Antoinette Laskey, MD, MPH – Children's Health Services Research
Dr. Laskey is a forensic pediatrician at the Indiana University School of Medicine, Riley Hospital for Children and Methodist Hospital in Indianapolis, Indiana. Dr. Laskey specializes in research on child abuse and child fatalities. She is the co-director of the Family Violence Institute at IU School of Medicine, a multi-disciplinary, campus wide community collaboration project dedicated to the research, education, clinical services and policy for all forms of family violence.
Gilbert Liu, MD, MS – Children's Health Services Research
Nancy Swigonski, MD, MPH – Children's Health Services Research
Dr. Swigonski belongs to the faculty of the General and Community Pediatrics and Public Health, and is an affiliate scientist of the Regenstrief Institute. Her research interests include underserved populations, access to health care, quality of health care, educational methods during residency and postgraduate training, and evaluation of Medical Home.
Rachel Vreeman, MD, MS
Sarah Wiehe, MD, MPH – Children's Health Services Research
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Inflammation/Innate Immunity
Jeffrey B Travers, MD, PhD – Pediatric Pulmonary Inflammation/Asthma Research Group
The Travers laboratory research focuses on understanding the mechanisms of skin inflammation, especially how keratinocytes respond to agents such as ultraviolet radiation and bacterial products. Ongoing studies examine how UV can produce novel oxidized glycerophosphocholines (ox-GPCs) that can act as either agonists for the platelet-activating factor or peroxisome proliferator-activated receptor-gamma receptors. Their studies using mice deficient in PAF and PPAR-gamma receptors suggest that these ox-GPCs are involved in UV effects, especially systemic immunosuppression. Projects are also characterizing the types of bacterial products found in infected atopic dermatitis skin lesions derived from patients, and how these products act to worsen skin disease. The studies in the lab involve in vitro keratinocyte cultures, as well as in vivo animal models of cutaneous inflammation, human studies of infants and children with atopic dermatitis, and adults with acute effects of UV radiation.
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International Health/Outcomes
Rachel Vreeman, MD, MS – Children's Health Services Research
Dr. Vreeman is an assistant professor of pediatrics in the Children's Health Services Research Program and a pediatrician at Riley Hospital for Children. In addition, she is co-director of pediatric research for the Academic Model Providing Access to Healthcare, an academic collaboration that provides comprehensive HIV treatment for over 80,000 patients in Kenya. Dr. Vreeman is also an affiliated scientist at the Regenstrief Institute and a faculty investigator with the Center for Health Policy and Professionalism Research. Dr. Vreeman's research work focuses on the development of instruments to improve children's health care within resource-limited settings.
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Medical Informatics
Aaron E Carroll, MD, MS – Children's Health Services Research
Stephen M Downs, MD, MS – Children's Health Services Research
Dr. Downs is the director of the Children's Health Services Research Program at the Indiana University School of Medicine, and the Associate Director for Decision Sciences at the Regenstrief Institute for Health Care. His research interests include computer-based decision effectiveness analysis and their application to guideline development and computer based decision support.
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Pediatric & Developmental Pharmacology/Personalized Therapeutics
Jamie Renbarger, MD
Dr. Renbarger is Assistant Professor of Pediatrics and Clinical Pharmacology and Associate Director of the Indiana Institute for Personalized Medicine. Dr. Renbarger's primary research interest as a pediatric oncologist is in personalized medicine and pharmacogenomics in the treatment of childhood cancers. Within that arena, much of her recent work has focused specifically on optimizing use of chemotherapies in the treatment of pediatric acute lymphoblastic leukemia. Her broad research objective is to improve the treatment of children with cancer by using genomics to target effective therapy, and to minimize what can be debilitating toxicities. Her work involves a major effort to identify biomarkers of drug toxicity and efficacy in the treatment of pediatric cancer. The ultimate goal is to use these biomarkers to develop simple, robust and practical clinical predictors of response to medications in individual patients that can be used to optimize dosing in the treatment of children, many of whom have curable malignancies.
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Stem Cell Biology
Merv Yoder, MD – Hematologic Malignancies and Stem Cell Biology Research Group
Dr. Yoder's lab is focused on the development of the hematopoietic system. They have identified hematopoietic stem cells in the murine yolk sac prior to the formation of the fetal liver. Their research efforts are focused on the following questions: 1) Where and when do hematopoietic stem and progenitor cells originate in the murine embryos? 2) Do yolk sac endothelial cells play a role in the formation, proliferation, and engraftment of yolk sac hematopoietic stem cells in vivo? 3 ) Will embryonic endothelial cells facilitate hematopoietic stem cell proliferation ex vivo with or without the addition of recombinant cytokines? These questions are being addressed using cell sorting and transplant assays with donor cells isolated from a variety of transgenic mice including mutant mice who fail to develop a heartbeat in utero. A second project is to understand the role played by several integrin molecules in supporting the adhesion, proliferation, and differentiation of primitive hematopoietic cells from the murine yolk sac. Using monoclonal antibodies, flow cytometry, and their novel transplantation assay they will determine whether the expression of specific integrin molecules can be used to further enrich for hematopoietic stem cells. A third project is to understand the interaction between human umbilical cord blood endothelial colony forming cells (ECFCs) and extracellular matrix molecules in determining the number and size of human blood vessels formed in vivo upon implantation into immunodeficient mice. Advances are translated into rodent wound healing models to find the most optimal ECFC/matrix combination that promotes wound healing in diabetic mice.
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For More Information
To see all researchers and current projects at the Herman B Wells Center for Pediatric Research go to www.wellscenter.iupui.edu
To see more about Children's Health Services Research go to www.ichsr.org
