Recognized Excellence of Division Trainees and Faculty

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

• Rachel Ernst and Tarah Wagner, summer students in the Rothenberg Lab, and mentored by Mark Rochman, PhD, won the Poster of Distinction at the Nutrition Research Day Poster Session at Cincinnati Children's for their work on peanut protein levels. Ernst and Wagner went on to take first place in the Agriculture / Food Science category at their high school's capstone competition on April 28.
• Justin Wheeler, MD, a clinical fellow in the Hogan Lab, was the recipient for the award for the 2017 AAAAI / APFED Best Oral Abstract on eosinophilic gastrointestinal diseases by a fellow-in-training at the 2017 American Academy of Asthma, Allergy & Immunology (AAAAI) Annual Meeting.
• Assistant professor, Ting Wen, MD, PhD, received a Trustee Grant Award by Cincinnati Children’s to support the Wen Lab in investigating the roles of FFAR3 in Th2 cytokine production by esophageal lymphocytes.
• Assistant professor, Andrew W. Lindsley, MD, PhD, received a K08 from the National Institute of Allergy and Infectious Diseases (NIAID). This National Institutes of Health clinical scientist career development award will support the Lindsley Lab in investigating how the sphingolipid ORMDL3 regulates dendritic cells in asthma.
• Assistant professor, Patricia C. Fulkerson, MD, PhD, received an R01 from National Institute of Allergy and Infectious Diseases (NIAID). This R01 will support the Fulkerson Lab in investigating the role of the transcription factor Aiolos in eosinophilic asthma.

p65: A Step Back from Sepsis

Sepsis is a life-threatening condition caused by the body’s response to infection injuring a person’s own organs and tissues and causing endotoxic shock. Sepsis is primarily caused by Gram-negative bacteria, which trigger immune cells and cytokines. A study, published in Innate Immunity, and led by Simone Vanoni, PhD, and our division’s director of research, Simon P. Hogan, PhD, demonstrates that lack of the protein p65, a part of the NF-κB transcription complex, in macrophages caused increased mortality in mice with endotoxic shock and that there is an association with the excessive production of proinflammatory cytokines. These findings identify a new role for NF-κB in the negative regulation of myeloid cell proinflammatory activity and function in sepsis.

Cadherin 26: Adhesion and Immunomodulation During Allergic Inflammation

Cadherins mediate diverse processes critical in inflammation, including cell adhesion, migration and differentiation. A recent study, published in Mucosal Immunology and led by Julie Caldwell, PhD, and Marc E. Rothenberg, MD, PhD, reported that an uncharacterized cadherin, cadherin 26 (CDH26), is highly expressed by epithelial cells in human allergic gastrointestinal tissue, such as the stomach tissue of patients with eosinophilic gastritis (EG) and esophageal tissue of patients with eosinophilic esophagitis (EoE). In vitro characterization revealed that CDH26 not only enhanced cellular adhesion through binding catenin and integrin, but also had an interesting inhibitory role when expressed as an Fc-fusion protein, with CDH26-Fc inhibiting activation of human CD4+ T cells in vitro, including secretion of IL-2. As CDH26 regulated leukocyte adhesion and activation, it may represent a novel checkpoint for immune regulation and therapy of eosinophilic gastrointestinal disorders (e.g., EG and EoE) via CDH26-Fc. A patent concerning this work was recently granted by the USA patent office.

Memory T Cell Epigenome Encodes Rapid Recall Ability

Even though T-cell receptor (TCR) stimulation with a co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage-specific cytokines much more rapidly than the naïve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. In a study published in Scientific Reports, Artem Barski, PhD, together with colleagues from the National Institutes of Health (NIH) and New York University, epigenetically profiled human resting naïve, central and effector memory T cells using ChIP-Seq and found that unlike the naïve cells, the regulatory elements of the cytokine genes in the memory T cells marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation associates with the deposition of positive histone modifications during memory T cell differentiation. The researchers propose a model of T cell memory, in which immunologic memory state encoded epigenetically, through poising and transcriptional memory.

Siglec-8: Engaging Eosinophil Cell Death

Activation of Siglec-8 receptor on human eosinophils leads to eosinophil reactive oxygen species production and cell death. A study published in Immunobiology and led by Dr. Nives Zimmermann, MD, evaluated the suspected role of Src family kinases (SFKs) in this pathway. They discovered the requirement of SFKs for the production of intracellular reactive oxygen species via this pathway and that both the reactive oxygen species and the requirement of SFKs for Siglec-8–induced cell death in activated eosinophils. Deciphering the molecular basis of eosinophil cell death may inform translational and clinical research, as accumulation of activated eosinophils can contribute to inflammation and damage in conditions such as asthma and eosinophilic gastrointestinal disorders.

Tissue Identity in Organ-specific Responses of Allergy

Despite systemic sensitization to the triggering allergens, allergic inflammation manifests in different organs—lungs, skin and esophagus for patients with asthma, atopic dermatitis and eosinophilic esophagitis (EoE), respectively. The disparity between the systemic trigger yet organ-specific response is not well understood. In a study published in The Journal of Allergy and Clinical Immunology, Mark Rochman, PhD; Jared Travers, PhD; and Marc E. Rothenberg, MD, PhD, assessed the potential role of organ-specific genes in the differential manifestation of allergy. They characterized the expression of esophagus-specific genes identified by The Human Protein Atlas Project, which maps the molecular signature of tissues, in esophageal biopsy specimens of patients with EoE, a chronic, inflammatory, food allergen–driven disorder of the esophagus. Strikingly, about 39% of esophagus-specific genes had altered expression in EoE biopsies, with the downregulation of approximately 90% of these genes. These findings reveal a profound loss of differentiation within the esophageal epithelium. The whole-exome sequencing revealed mutations in several esophagus-specific genes in EoE tissue. Notably, prior research showed that the gene most strongly associated with EoE disease risk, CAPN14, encodes an esophagus-specific protease. These collective findings suggest that the pathogenesis of EoE involves a loss of esophageal differentiation and expand our understanding of the propagation of allergic inflammation on the level of tissue molecular identity, suggesting that genetic profiling of tissue-specific genes may have diagnostic and prognostic value for EoE and potentially other allergic conditions.

2017 NIAID Addendum Guidelines for Preventing Peanut Allergy

In 2015, findings from a landmark National Institute of Allergy and Infectious Diseases (NIAID)-funded clinical trial, called the Learning Early About Peanut (LEAP) study, showed that introducing peanut-containing foods to infants at high risk for developing peanut allergy was safe, and led to an 81% relative reduction in the subsequent development of peanut allergy. Due to the strength of these results, NIAID established a coordinating committee that convened an expert panel to update the 2010 Guidelines to specifically address the prevention of peanut allergy. The division's director of clinical services, Amal H. Assa'ad, MD, contributed through service on the coordinating committee and expert panel to these Addendum Guidelines for the Prevention of Peanut Allergy in the United States published in the January 2017 issue of Annals of Allergy and Immunology along with an editorial by Amal H. Assa'ad, MD. These addendum guidelines are a major paradigm reversal by recommending early peanut introduction to infants, the importance evidenced by these guidelines published in seven prestigious journals in the fields of allergy, dermatology, nutrition and general pediatrics. Read the National Public Radio segment (by Patti Neighmond), the Reuter's article (by Rob Goodier), and a related Journal of Allergy and Clinical Immunology editorial about the LEAP study findings about early allergen consumption.

Food Allergy Desensitization and Tolerance Induction and Disparities

Clinical trials for the desensitization and induction of tolerance in children and adults with food allergy continued with the contributions of our division’s director of clinical services, Amal H. Assa’ad, MD; physicians, such as Michelle B. Lierl, MD, and Stephanie L Logsdon, MD; fellows; research nurses and coordinators; and the Shubert Clinic. Completed studies include epicutaneous immunotherapy (known as the peanut patch, and manufactured as Viaskin®), oral immunotherapy for peanut allergy and oral immunotherapy for multiple food allergens, with the last employing an anti-immunoglobulin E under the marketed name of Xolair® (omalizumab) to reduce the incidence of side effects that accompany oral immunotherapy. The peanut (LAMP-based) vaccine study was also initiated, with participants progressing from randomized, placebo-controlled trials to a higher dose phase. Furthermore, Amal H. Assa’ad, is collaborating in National Institutes of Health (NIH)-funded research to examine racial and ethnic disparities in food allergy, the FORWARD study, showed that children who were parent-identified as African American, or Hispanic, had different food allergen profiles, higher rates of associated atopic conditions, and increased rates of food allergen–associated anaphylaxis and emergency department visits than children who were parent-identified as Caucasian.

Physician Receives 2017 Clinical Care Award

The Faculty Awards Committee at Cincinnati Children's selected Michelle B. Lierle, MD, for the Clinical Care Award. This is a well-deserved honor for Dr. Lierl, who is now in her 30th anniversary year at Cincinnati Children's. In addition to her great clinical service, Dr. Lierl researches fungal allergens and has created a fungal spore photo website.

Fellowship Director Receives 2017 AAAAI Distinguished Service Award

The American Academy of Asthma, Allergy & Immunology (AAAAI) selected the director of our Allergy / Immunology Fellowship Program, Kimberly A. Risma, MD, PhD for their 2017 Distinguished Service Award based on her leadership with the Chrysalis Project. The Chrysalis Project is a program for medical students and internal medicine and/or pediatric residents that provides them the opportunity to explore a career in allergy / immunology. Housed within the AAAAI Annual Meeting, it includes pairing the Chrysalis mentee with a fellow-in-training mentor, didactic lectures with allergy/immunology faculty, career option presentations, and free conference registration and access to the leading knowledge in the hundreds of AAAAI meeting sessions, workshops, symposia, seminars and oral abstracts. Dr. Risma has helped to propel this program to become a jewel of our society; thus greatly impacting our field and its future. Through her efforts, she has established a ‘pipeline’ of strong physicians in our field. In 2010, Dr. Risma received a nomination from the Board of AAAAI to assume the co-Chair position of the Chrysalis Program Project after a pause in the program's funding. Under her leadership, the program has expanded from 20 to 50 attendees per year. The Chrysalis Project has been extraordinarily well received as evident from the growing number of highly qualified applicants and attendees, the positive reviews, and the growing number of fellowship applicants who credit the Chrysalis Project.