Recognized Excellence of Allergy and Immunology Division Trainees, Fellows, and Associates

The Division of Allergy and Immunology is proud of the excellence of its undergraduate and graduate trainees, postdoctoral research and clinical fellows and associates. Several received recognition for their achievements throughout the year:

• Andrea Szep, an undergraduate student at the University of Cincinnati, won second place for her Summer Undergraduate Research Fellowship Program Capstone presentation investigating gene expression patterns of eosinophils in human eosinophilic esophagitis. Andrea Szep received mentoring from Julia Dunn, PhD, and Marc Rothenberg, MD, PhD.
• Kurtis Stefan, a predoctoral student of the Molecular and Developmental Biology Program, received an award of a NIAID F30 (F30 AI157421) “Silencer Control of T cell Homeostasis and Activation” under the mentorship of Artem Barski, PhD.
• Tetsuo Shoda, MD, PhD, a research associate in the Rothenberg CURED Lab in fiscal year 2022, received an NIH K99/R00 “Combinatory Effects of Genetic Variants in Eosinophilic Esophagitis” and appointed as an assistant professor in Division of Allergy and Immunology for fiscal year 2023.
• Susan Xie, MD, a second-year fellow of the Allergy and Immunology Fellowship Program contributed two publications under the mentorship of Kimberly A. Risma, MD, PhD.
• Simin Zhang, MD, a third-year fellow of the Allergy and Immunology Fellowship Program, contributed one publication, researched the roles of mast cells in eosinophilic esophagitis, and received a Stimulating Access to Research in Residency (StARR) Award from the Department of Internal Medicine at University of Cincinnati for her proposal entitled, “Esophageal epithelial recruitment of mast cells and subsequent activation” under the mentorship of Rothenberg.
• Katharine Guarnieri, MD, a first-year research fellow of the Advanced Research Training Fellowship Program, contributed three publications under the mentorship of Michelle Lierl, MD, Sandra Andorf, PhD, Rothenberg, and Risma. Guarnieri's three main areas of research include: 1) Collaborating with the Food Allergy Research & Education (FARE) to characterize individuals with food allergy with and without eosinophilic esophagitis, 2) Evaluating the impact of eosinophilic esophagitis disease activity on asthma measures in children with comorbid eosinophilic esophagitis and asthma, and 3) Characterizing amoxicillin-associated reactions presenting to the emergency department.
• Steven Proper, DO, PhD, a second-year research fellow of the Advanced Research Training Fellowship Program, contributed one review publication on precision medicine in allergic diseases under the mentorship of Nurit Azouz, PhD, and accepted a faculty position as an allergist / immunologist assistant professor of pediatrics and adolescent medicine at Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI.
• A special thank you to Stephanie L. Ward, MD, for her continued leadership in educational mentorship of medical students with the University of Cincinnati, including being the chair for the fellowship Clinical Competency Committee of Cincinnati Children’s for Accreditation Council for Graduate Medical Education (ACGME).
• A special thank you to Risma for her continued leadership in educational mentorship of allergy / immunology fellows and as leader of the Allergy / Immunology Fellowship Program and co-director of the Advanced Research Training Fellowship Program.

Function of Immune Cells In Situ: New Faculty Ty Troutman, PhD

The division welcomes Ty Troutman, PhD, as a faculty member. The Troutman Lab investigates the functions of tissue-residing myeloid cells, including macrophages, in regulating health and disease. Macrophages reside in all tissues, where they contribute to innate immune surveillance, clear cellular debris and promote repair in response to injuries. In addition, macrophages and other recruited myeloid cells participate in disease processes associated with obesity, allergic inflammation, suppression of anti-cancer immunity and neurodegeneration. Within each tissue, myeloid cell subtypes adopt specialized roles through unique combinations of niche-provided signals. As a result, myeloid cells may diversify further during disease because of environmental perturbation. The Troutman Lab researches the function of immune cells in situ, which can lead to novel findings potentially missed from in vitro systems. Current lines of research include transcriptional regulation of tissue myeloid cells (eosinophils, macrophages) during aging and disease (collaborative with the Deepe, Rothenberg CURED, and Pasare Labs) and functional and molecular diversification of esophageal myeloid cells (eosinophils, macrophages, mast cells) during the disease eosinophilic esophagitis (collaborative with the Rothenberg CURED and Schwartz Labs). The Troutman Lab couples cellular and molecular immunology approaches to quantitative analyses of dynamic epigenetic factors ultimately controlling gene expression to discover novel intercellular and intracellular mechanisms controlling tissue myeloid cell behaviors during health and disease. Learn more about the Troutman’s Molecular Cell review of exploiting dynamic enhancer landscapes to decode macrophage and microglia phenotypes in health and disease.

Proteolytic Breakdown of Immunologic Tolerance

Azouz leads the Azouz Lab in researching allergic diseases and the mechanisms by which protease–protease inhibitor imbalance promotes barrier breaches and loss of immunologic tolerance in the development of allergic diseases. A breakdown of immunologic tolerance appears to be a key feature in allergic diseases. The mechanisms underlying the break of tolerance are not well understood and involve a combination of environmental and genetic factors. The epithelium is the first line of defense against potential insults, providing a physical barrier between the host and the external environment. Clinical observations of atopic or allergic march, which is the natural history or typical progression of allergic diseases that often begin early in life, supports the importance of epithelial integrity in the development of allergic disease . These include atopic dermatitis (eczema), food allergy, allergic rhinitis (hay fever) and asthma. At a barrier breach, harmless antigens may encounter immune cells, potentially leading to production of a danger signal and priming a break in immune tolerance and an allergic response. The Azouz Lab investigates the function and regulation of proteases in host defense and in the onset and propagation of inflammatory and allergic diseases and focuses on deciphering the role of proteases and their inhibitors in the epithelium as part of homeostatic and surveillance mechanisms. As loss of protease inhibitors and alterations of proteolytic activity lead to tissue damage and may exert a paramount signal in the development of inflammatory diseases, the Azouz Lab also focuses on deciphering the molecular mechanisms that disrupt the balance between proteases and protease inhibitors and developing strategies for controlling proteolytic activity as an approach to treat immune diseases. For instance, in fiscal year 2022, the Azouz Lab collaboratively investigated how a novel class of transmembrane protease, serine 2 (TMPRSS2) inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells.

Specialized Care for Food Allergy in Infancy

Ashley L. Devonshire, MD, MPH, leads a specialized Beginning Introduction To Allergens Early (BITE) Clinic for the prevention, early identification, and management of food allergy in infancy. The BITE Clinic sees infants who are at risk for food allergy or who already have food allergies. Devonshire’s research investigating the molecular signature of CD4+ T cells in infants with clinically reactive peanut allergy versus infants with peanut tolerance receives support from a KL2 Research Scholar Award from the Center for Clinical and Translational Science and Training (CCTST) at the University of Cincinnati. Resulting data will aid in the development of tools for food allergy diagnostics in infants and expand our knowledge of food allergy in the understudied infant population. In fiscal year 2022, Devonshire published research about whole blood transcriptomics identifying gene expression associated with peanut allergy in infants at high risk, epigenetic and transcriptional dysregulation in CD4+ T cells in patients with atopic dermatitis, and an assessment of caregiver anxiety during early peanut introduction clinics. Furthermore, Sandy Durrani, MD, made key progress in developing early infant food allergy screening for in-clinic use. Learn more about the Devonshire Lab.

Functions Before Lineage Commitment

Justin Schwartz, MD, PhD, is a physician-scientist with the Division of Allergy and Immunology and the CCED, where he provides clinical care for patients with eosinophilic disease. Schwartz's research training is in basic and translation science with expertise in innate immune function and eosinophil biology. The Schwartz Lab research focuses on understanding how allergic progenitor cells participate in the pathophysiology of eosinophilic gastrointestinal disease (EGID), with a goal of advancing our understanding of disease mechanisms to identify potential novel therapeutic targets and biomarkers for disease monitoring. He investigates eosinophil progenitors (EoPs), which are lineage–committed CD34+ progenitor cells that primarily reside in the bone marrow but can mobilized into the peripheral blood during allergic immune responses and accumulate at sites of allergic inflammation. EoP levels in the peripheral blood of patients with active eosinophilic esophagitis (EoE) are significantly increased, and levels for use to differentiate active disease from inactive disease with high sensitivity, suggesting that EoP levels could serve as a potential disease biomarker. The functional significance of mobilized EoPs remains unclear, but these cells could propagate local tissue inflammation through in situ proliferation and maturation and secretion of inflammatory cytokines. In fiscal year 2022, Schwartz collaboratively published research about the transcription factor Aiolos regulating eosinophil migration into tissues and the eosinophil-mediated suppression and anti–IL-5 enhancement of plasmacytoid dendritic cell interferon responses in asthma and published a key consensus statement with updated nomenclature for EGIDs. These nomenclature updates may lead to shared language, disease diagnosis, study design, and outcome evaluation that would hasten therapeutic development.

Approaching Immune Mechanisms with Systems Biology and Omics Data

Barski uses and develops multi-omics techniques to investigate allergic mechanisms. The Barski Lab researches epigenomics with a primary focus on the immune system and research projects designed to investigate epigenomic regulation of T cell differentiation, activation and memory. To support these projects, the Barski Lab runs a complete “-omics” kitchen, including both wet lab “-omics” biotechnology and dry lab data analysis. Their expertise in both areas led to multiple collaborative papers and grant applications on topics ranging from the epigenomics of spermatogenesis to the epigenomics of atopic disease to epigenomics of lung development. The Barski Lab also runs the SciDAP server as the Cincinnati Children’s Epigenomics Data Analysis Core. Through his research in the Barski Lab and leadership as director of the Epigenomics Data Analysis Core, Barski publishes research and methodology such as the following publications in fiscal year 2022 in Frontiers in Immunology, STAR Protocols, Journal of Immunology, and Mucosal Immunology.

An Epithelial Allergen Sensor RipIL33

Interleukin-33 (IL-33) plays a central role in type 2 immune responses and is generally thought that it releases following cellular damage and processes extracellularly. Michael Brusilovsky, PhD, and Rothenberg led a study in collaboration with Chandrashekhar Pasare, DVM, PhD, describing a novel ripoptosome pathway assembled following exposure to various unrelated environmental allergens and that processes IL-33 into an active form intracellularly, thereby identifying an Epithelial Allergen Sensor - RipIL33. Publication of this study is in Nature Immunology and featured in a Cincinnati Children's science blog post. “The discovery of this mechanism is the most important breakthrough in understanding how the innate immune system senses allergens, a question that has puzzled immunologists for a long time,” says Pasare.

Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-site Study

Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGID) or inflammatory bowel disease (IBD) is something previously undetermined. This study of EoC, led by Shoda and Rothenberg, establishes the basis for EoC’s diagnosis and unique characteristics, including establishing EoC transcriptomic profiles, identifying mechanistic pathways, and integrating findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment. This study is the cover story of the Gastroenterology May 2022 issue, and a feature in a Cincinnati Children's science blog post.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk

Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Shoda and Rothenberg led a collaborative team investigating gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences. Notably, they found that tetraspanin 12 (TSPAN12) was the gene most correlated with fibrostenosis. Furthermore, TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System, with lower TSPAN12 associating with smaller esophageal diameter, increased lamina propria fibrosis, and genes enriched in cell cycle-related pathways. Patients with fibrostenotic EoE expressed decreased levels of endothelial TSPAN12. Esophageal endothelial cells expressed TSPAN12, and deficiency of TSPAN12 promoted the release of endothelial cells factors that promoted pro-fibrotic processes. Interestingly, IL-13 in vitro downregulated TSPAN12, and treatment of patients with anti–IL-13 antibody increased TSPAN12. These findings suggest that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk. A publication on this study is in Gastroenterology and is on the journal’s cover.

Host-Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation

The importance of gut microbes in health and disease is the focus of recent public media. Brusilovsky and Rothenberg led a study investigating fundamental properties of host-microbiota interactions in the esophagus and established the composition, transplantation potential, antibiotic responsiveness, and host-microbiota interactions of the esophagus. Fecal matter transplantation reconstituted the esophageal microbiome, opening up fecal transplants as a consideration for treating esophageal disease. Antibiotic usage is a predisposition to allergic disease in an eosinophilic esophagitis (EoE) experimental model in mice. The findings have implications for understanding health and disease in the esophagus and managing EoE. A publication on this study is in Gastroenterology and featured in a Cincinnati Children's science blog post.

Transition and Adult Primary Immune Deficiency Program

Cincinnati Children’s is a worldwide leader in the diagnosis and treatment of primary immune deficiency diseases. More immune deficiency diseases are now recognized in adults, and children with primary immune deficiencies eventually need to transition to adult care providers. To fill these important care needs, Erinn S. Kellner, MD, is the founder of the Transition and Adult Primary Immune Deficiency Program, which focuses on the complex needs of adults and adolescents with primary immune deficiencies and basic, translational and clinical research to understand the mechanisms of different immune deficiencies and how they may change over time. The Transition and Adult Primary Immune Deficiency Program collaborates with adult subspecialty services at the University of Cincinnati and the Cincinnati Children’s Diagnostic Immunology Laboratory and Immune Deficiency and Histiocytosis Program. Learn more about the Kellner Lab.

Drug Allergy Program

The Drug Allergy Program, led by Risma diagnoses and treats drug allergies in children in the Greater Cincinnati area and in patients referred nationally. The Drug Allergy Program is one of few pediatric drug allergy programs in the country. An important aspect of the program is “de-labeling” drug allergies by testing children for a clinical reaction to the drug in a controlled setting. For instance, recent studies show that 95% of children labeled as having an “allergy” to amoxicillin do not have a clinical reaction when re-exposed to it through testing. De-labeling drug allergies prevents use of alternative drugs that may cost more, have more side effects, or contribute to increased antibiotic resistance in our communities. At Cincinnati Children’s, 7.5% of all patients have a “penicillin allergy” on their medical history. Since 2019, the Penicillin Allergy Testing Services (PATS) team successfully de-labeled >1,500 patients previously “allergic” amoxicillin and enhanced perioperative anaphylaxis testing by adding documentation flowsheets, note templates, and note writer capacity to the EPIC electronic medical record (EMR) system. They are currently pursuing opportunities to build a new clinical registry for drug allergies. Overall, the PATS team sensitively and systematically addressed a previously unmet need by creating and expanding a visionary program that changes the outcome for the better for children, families and colleagues.

Food Allergy Program

The Food Allergy Program, led by Amal H. Assa’ad, MD, improves the lives of patients with food allergies and their family members by providing expert care, innovative treatments and cutting-edge research. In addition to providing patient services, engaging in nine clinical trials on diverse topics including eczema, food allergy and urticaria and leading the field in improving oral immunotherapy protocols, the Food Allergy Program receives support from three key research awards (R21, R01, FARE). The Program is a Food Allergy Research & Education (FARE) Clinical Research Center of Distinction and the FARE Clinical Network Biobank and Biomarker Discovery Center. It published 10 publications in fiscal year 2022 in the Journal of Allergy and Clinical Immunology: In Practice, the Journal of the Academy of Nutrition and Dietetics, the Annals of Allergy, Asthma and Immunology, Clinical & Experimental Allergy, the Journal of Allergy and Clinical Immunology, and the World Allergy Organization Journal. The Food Allergy Program team comprises coordinators, nurse coordinators and faculty.

Cincinnati Center for Eosinophilic Disorders

Cincinnati Children’s is a worldwide leader in the diagnosis, treatment and research of eosinophilic disorders. The Cincinnati Center for Eosinophilic Disorders (CCED), established in 2001 by Rothenberg, was the first of its kind to focus solely on these complex medical conditions in children and adults. Today, patients with eosinophilic disorders travel from all over the country and different parts of the world to receive comprehensive care at Cincinnati Children’s. Our specialists engage in extensive research efforts to enhance the understanding of these disorders, fuel the development of novel therapies and find a cure. In fiscal year 2022, the CCED published 68 publications on eosinophilic disorders, established transnasal endoscopy (TNE) at Cincinnati Children’s, and supported 15 ongoing basic, clinical and translational studies.

Multicenter Consortium on Eosinophilic Disorders

Led by Rothenberg and Glenn Furuta, MD, the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) continues to further research and develop clinical expertise, train clinical investigators, pilot clinical research projects and provide access to information related to eosinophilic gastrointestinal disorders (EGIDs) for basic and clinical researchers, physicians, patients and the lay public. The belief is that allergic hypersensitivity to certain foods and an over-accumulation in the gastrointestinal tract of white blood cells, called eosinophils, trigger chronic inflammatory conditions. Eosinophilic disorders can cause a variety of gastrointestinal complaints, including reflux-like symptoms, vomiting, difficulty swallowing, tissue scarring, fibrosis, the formation of strictures, diarrhea, abdominal pain and failure to grow in childhood. CEGIR receives funding from the Rare Diseases Clinical Research Network (RDCRN) and comprises researchers from 16 institutions and three major patient advocacy groups, including the Campaign Urging Research for Eosinophilic Disease (CURED), American Partnership for Eosinophilic Disorders (APFED), and the Eosinophilic Family Coalition (EFC). Notably, CEGIR initiated a Diversity Committee, which is very active (>30 members) becoming exemplary for the RDCRN. CEGIR’s Diversity Committee has a number of research and education objectives, which are actively underway. The Diversity Committee also generated a Diversity Vision Statement for CEGIR, “CEGIR actively promotes a culture of diversity and inclusivity in its membership, its innovative research studies and its educational initiatives”, read at the beginning of all biweekly meetings.

Industry Clinical Trials

The Division of Allergy and Immunology at Cincinnati Children's believes that research is the hope for future clinical advances in care and treatment. In fiscal year 2022, there were four newly initiated clinical trials in the division. Amal H. Assa'ad, MD, leads an investigation into the safety and clinical efficacy of a therapeutic for peanut allergy with Novartis Pharmaceuticals: "A 52 Week, Multi-center, Randomized, Double-blind Placebo-controlled Study to Assess the Clinical Efficacy and Safety of Ligelizumab (QGE031) in Decreasing the Sensitivity to Peanuts in Patients With Peanut Allergy" (ClinicalTrials.gov Identifier: NCT04984876). Marc Rothenberg, MD, PhD, is leading two trials investigating treatments for eosinophilic disorders: 1) "A Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis" with Astrazeneca (ClinicalTrials.gov Identifier: NCT04543409) and 2) "A 52-week, Open-label, Single Arm Study to Investigate the Efficacy and Safety of Mepolizumab SC in Participants Aged 6 to 17 Years With Hypereosinophilic Syndrome" with GlaxoSmithKline (Syneos Health) (ClinicalTrials.gov Identifier: NCT04965636). Sandy Durrani, MD, leads one trial investigating the efficacy and safety of a treatment in adult patients with active eosinophilic duodenitis (EoD): "A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Duodenitis Who Have an Inadequate Response With, Lost Response to, or Were Intolerant to Standard Therapies" with Allakos, Inc. (ClinicalTrials.gov Identifier: NCT04856891).