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2013 Hope APFED/ARTrust™ Pilot Grant Award
The 2013 Hope APFED/ARTrust™ Pilot Grant Award is the result of a collaborative effort between APFED and the Allergy, Asthma & Immunology Education and Research Organization, Inc. (ARTrust™), and was established to allow investigators from a variety of disciplines to initiate new projects relevant to eosinophilic diseases, with a focus on the development of new ideas which are likely to lead to future external funding. Please join us in congratulating the recipient of this year's award, Dr. Seema Aceves.
Seema Aceves, M.D., Ph.D.
Associate Professor of Allergy and Immunology
University of California in San Diego
Hope APFED/ARTrust™ Pilot Grant Award Amount: $140,000 over a 2-year period, co-funded between APFED and ARTrust™
Project: Novel epithelial markers for tissue fibrosis in pediatric eosinophilic esophagitis
Scarring, or fibrosis, can cause permanent damage to the esophagus, impairing swallowing. Dr. Aceves will explore factors leading to esophageal damage in children with eosinophilic esophagitis, and investigate the effect of a medication on process.
Patient Impact: Developing ways to detect fibrosis, and understanding the causes of fibrosis, will enable investigators to better study this disease process and develop new treatments.
2013 HOPE Pilot Research Grants
APFED is proud to support two HOPE Pilot research grants in 2013. Dr. Praveen Akuthota and Dr. Yui-Hsi Wang are the recipients of the $50,000 awards. Please join us in congratulating them for their grant-winning proposals. We look forward to their many valuable contributions to eosinophil research.
Praveen Akuthota, M.D.
Division of Pulmonary, Critical, & Sleep Medicine
Division of Allergy and Inflammation
Beth Israel Deaconess Medical Center
Instructor, Medicine, Harvard Medical School
HOPE Pilot Grant Amount: $50,000 for a 1-year period
Project: Mechanistic Effects of Eotaxin-3 on Human Eosinophils
Dr. Akuthota’s research will provide a greater understanding of eotxain-3 on eosinophils in a variety of eosinophil associated diseases including the Churg Strauss syndrome, which can affect the lungs, sinuses and other organs. Eotaxin-3 is thought to regulate eosinophil trafficking to the airways and gastrointestinal tract. His research will lead to better mechanistic understanding of the role of this signaling molecule in eosinophil associated diseases.
Patient Impact: Understanding the role of eotaxin-3 in eosinophil associated diseases will potentially lead to new treatments.
Yui-Hsi Wang, Ph.D.
Allergy and Immunology
Cincinnati Children’s Hospital Medical Center
HOPE Pilot Grant Amount: $50,000 for a 1-year period
Project: Role of type-2 innate lymphoid cells in EGID
Dr. Wang's research on eosinophil associated gastrointestinal disorders will focus on understanding the role of cytokines, specifically IL 25, in small intestinal eosinophil infiltration. Cytokines, a part of the immune system, play a role in ‘signaling’ or calling the eosinophils to accumulate in the GI tract.
Patient Impact: Understanding the role of the immune system in eosinophil associated gastrointestinal disorders, such as eosinophilic gastroenteritis, may lead to development of new immune-based treatments.
2012 HOPE Grant Recipients
APFED is proud to announce the recipients the 2012 HOPE Research Grants. The applications for this year were uniformly strong, making funding decisions difficult. After a thorough review process, APFED would like to congratulate Dr. Mei-Lun Wang (Children's Hospital of Philadelphia) and Drs. Amir Kagalwalla (Children's Memorial Hospital, Chicago, IL), Barry Wershil (Children's Memorial Research Center, Chicago, IL), and Steven Ackerman (University of Illinois, Chicago) on receiving the HOPE faculty Grants. The HOPE Pilot Grant recipients are Dr. Lisa Spencer PhD (Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA) and Dr. Kathryn Peterson MD (University of Utah, Salt Lake City, UT)
Dr. Wang's research proposal is entitled "Esophageal Epithelial and Mesenchymal Cross-Talk in Eosinophilic Esophagitis". Clinically, subepithelial fibrosis is an important feature of EoE, with mechanisms of this process poorly understood. Dr. Wang's preliminary data suggest that fibroblasts can sense epithelial damage, and may prime profibrotic responses to epithelial food antigen exposure. Her research team will characterize epithelial-fibroblast interactions using culture systems in which the two cell types can be co-cultured within distances of microns. They will also test functional consequences of specific stimuli such as epithelial damage, acid/bile, and food antigens upon fibrogenesis using cell culture models using primary human esophageal epithelial cell lines. Dr. Wang's research would greatly help elucidate the mechanisms of subepithelial fibrosis, and hopefully lead to therapies that would help prevent the clinical problems of dysphagia, esophageal strictures, and food impactions.
Drs. Kagalwalla's, Wershil's, and Ackerman's research proposal seeks to "identify a panel of non-invasive biomarkers in the blood and/or urine of subjects with eosinophilic esophagitis (EoE) for the diagnosis and assessment of remission, recurrence or exacerbation of disease, as well as novel markers for responses to therapeutic intervention." Their collaborative plan includes correlation of levels of inflammatory biomarkers (including mast cell, eosinophil, chemokine, interleukin, and growth factor biomarkers) from samples obtained from blood, urine, esophageal biopsies, and intraluminal esophageal string test. They propose to validate the non-invasive protein biomarker panel by measuring mRNA expression in esophageal biopsy samples. This research has the potential to fulfill the extremely important clinical need of finding a noninvasive and readily accessible method of assessing for the presence and activity of EoE, hopefully reducing the need for diagnostic endoscopies and biopsies in managing the disease.
Dr. Spencer’s proposal focuses on cytokine production by murine GI eosinophils, and tests the ability of GI eosinophils to behave as antigen-presenting cells. Per Dr. Spencer, her “work has probes the preformed cytokine potential of human blood eosinophils, the mechanisms by which eosinophils elaborate intracellular cytokines from preformed granular stores, and most recently, the role(s) of autocrine Notch signaling in eosinophil activation. This work has contributed to the growing body of data supporting nontraditional roles for eosinophils regulating both the immune microenvironment and tissue homeostasis”. Her intent is to “apply our broad expertise in the basic immunobiology of eosinophils to outstanding mechanistic questions in eosinophilic gastrointestinal diseases, thus establishing a new research avenue in the laboratory.” Her goals are to help to mechanistically define epidemiological correlations between allergic diseases (i.e. asthma) and GI disorders and suggest prophylactic approaches for early detection and treatment of patients. Dr. Spencer plans to generate data from the pilot grant to apply for additional funding.
Dr. Peterson’s proposal seeks to use an esophageal brush to detect MBP-1 in the esophagus “To determine the relationship between MBP-1 and fluorescence intensity and to determine the surface density of MBP-1 on cytology brush bristles as a function of the number of brushings colorimetric assays provide a rapid non-invasive approach to diagnose and monitor a wide variety of eosinophilic disorders.” Dr. Peterson intends to extend her assay to detect eosinophil involvement in eosinophilic gastroenteritis, eosinophilic asthma/Churg-Strauss, allergic sinusitis and eosinophilic cystitis. Her approach provides a less invasive path to monitor progress of each disease and response to therapy. Dr. Peterson plans to use data generated from this to obtain additional NIH funding to further develop the assay as a minimally invasive test to evaluate esophageal eosinophilia that can be performed at the bed side.
2011 HOPE Grant Recipients
Drs. Friedman and Spergel’s project involves the measurement of microRNAs (miRNA) in patients’ serum obtained via blood sample. miRNAs are short ribonucleic acid molecules that are important in regulating gene transcription and translation. Dr. Friedman’s research in Crohn’s disease has already shown distinct miRNA patterns in this patient population, and his proposed research aims to identify distinct miRNA expression patterns in patients with biopsy proven eosinophilic esophagitis (EoE) compared to patients with normal esophagus. His team hopes to correlate the miRNA expression to the severity of EoE on esophageal biopsy, thereby providing a noninvasive method of diagnosing and monitoring EoE disease activity through a simple blood test.
Drs. Ackerman and Furuta are collaborating on a project involving the esophageal string test (EST). The EST involves swallowing a small capsule with an attached string, with the process being minimally invasive compared to endoscopy and biopsy. The capsule can be swallowed with water or some pudding, while holding onto its attached string. The capsule breaks off in the intestine, and the end of the string dwells in the duodenum for a given period of time; then the string is removed and sent for analysis. The string directly samples esophageal secretions that contain potential EoE biomarkers from inflammatory cells. Their preliminary data have shown a nice correlation of EST sampling to EoE disease activity as determined by tissue biopsy. Funding for their project will help the researchers validate and improve the diagnostic accuracy of the EST and validate its use to monitor disease activity with treatment.
APFED 2011 HOPE Junior faculty grant recipient
Dr. Ariel Munitz will work in conjunction with Dr. Marc Rothenberg’s group in Cincinnati. His work focuses on eosinophil research and the role of inhibitory receptors in eosinophils. Dr. Munitz research career goals are aimed at defining molecular pathways that regulate eosinophil activity in health and disease. HOPE Grants are funded by donations to the HOPE on the Horizon Fund and by fundraisers hosted by families and friends of those living with eosinophil associated diseases.
APFED 2010 HOPE Junior Faculty Grant Recipient
Sophie Fillon, PhD Dr. Fillon University of Colorado Denver School of Medicine is working on research to determine the role of the microbiome in children with eosinophilic esophagitis (EoE). Dr. Fillon’s long-term goal is to become a leader in the field of EGIDS and to mentor a younger generation of students and post-doctoral fellows to enter into this nascent field. “This APFED HOPE award provides me with an outstanding opportunity to develop this line of research and would provide me with my first step in my junior faculty career.”
APFED 2009 HOPE Junior Faculty Grant Recipients
Antonella Cianferoni MD, PhD Dr. Cianferoni is an Assistant Professor of Pediatrics at the University Of Pennsylvania School Of Medicine and the Children's Hospital of Philadelphia in the Division of Allergy and Immunology. Dr. Cianferoni’s research focus is identification of novel genes and biomarkers that will add to the understanding, treatment and management of eosinophilic gastrointestinal diseases. Dr. Cianferoni writes: “I am in the process of establishing a research program aimed to the understanding of the basic pathogenetic mechanisms of eosinophilic gastroeneteropathies. There is a great need to expand understanding and to identify novel pathogenetic mechanisms of EE and to identify biomarkers that will lead to better diagnostic tools and treatments of this still elusive disease.”
Carine Blanchard PhD Dr. Blanchard is a Postdoctoral fellow and research instructor at Cincinnati Children’s Hospital and Medical Center in the Division of Allergy and Immunology, focusing on the molecular pathogenesis of Eosinophilic Esophagitis and food allergy related disorders. Dr Blanchard writes: “My research will focus on mechanisms that induce eosinophilic disease, with the goal of ameliorating the pain and distress of eosinophilic esophagitis. If we truly uncover a major role for Uroplakin 1B in EE diagnosis, then this would lead to further studies aimed at trying to understand the fundamental basis of the disease pathology and pathogenesis.
APFED 2008 HOPE Junior Faculty Recipient
Seema Aceves MD, PhD for her research "Tissue remodeling in pediatric eosinophilic esophagitis: Influence on prognosis and response to corticosteroid therapy". Dr. Aceves is an adjunct assistant professor of pediatrics at the University of California San Diego.
APFED trainee grant recipients
Miguel Stein, MD Cincinnati Children's Hospital Medical Center “Anti-IL-5 (Mepolizumab) Therapy in Hypereosinophilic Syndromes and Eosinophilic Esophagitis: Cytokine Secretion and Decreased Peripheral Blood Eosinophilia”
Thuy Anh Le, MD Feinberg School of Medicine “Distinct Allergic Predisposition of Children and Adults with Eosinophilic Esophagitis”
Elizabeth A. Schaefer, M.D, Riley Hospital for Children Indiana University School of “ORAL PREDNISONE (P) IS NOT SUPERIOR TO TOPICAL FLUTICASONE (F) IN THE TREATMENT OF ALLERGIC EOSINOPHILIC ESOPHAGITIS (AEE)”
Vincent Mukkada, MD The Children's Hospital of Denver/University of Colorado Health Sciences Center “EOSINOPHILS ENHANCE INTESTINAL EPITHELIAL BARRIER”
Samantha Woodruff, MD University of Colorado Denver School of Medicine and The Children's Hospital in Denver, Colorado “EoE lamina propria contains increased fibrosis”
Guangju Luo MD University of Cincinnati “Coexistence of eosinophilic esophagitis (EE) and celiac disease (CD)”
Brad Shepherd M.D. Vanderbilt University “Eosinophilic Esophagitis: Dilate or Medicate?”
Joanne Masterson, PhD University of Colorado Denver School of Medicine “Eosinophilic ileitis and tissue remodeling in the SAMP1/SkuSic mouse strain”
Anup Patel, MD Stanford University “Eosinophils Can Induce T cell Activation in Eosinophilic Esophagitis”
Eitan Rubenstein, MD University of California, San “Anti-Siglee-F Antibody Reduces Eosinophilic Inflammation in a Mouse Model of Eosinophilic Esophagitis”
Julie Caldwell, PhD Cincinnati Children's Hospital Medical Center “Microarray Analysis of Eosinophilic Gastritis Identifies a Strong Link with Cadherin-like 26 Overexpression”
Joseph Sherill PhD Cincinnati Children's Hospital Medical Center "Dysregulation of the Desmosomal Cadherin Desmoglein-l in Eosinophilic Esophagitis"
EunJin Lim PhD Cincinnati Children's Hospital Medical Center “Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CBP mediated histone-3 acetylation”
Letters of Appreciation - Researchers express gratitude for grants received through APFED's Hope on the Horizon Research Fund.