Marc E. Rothenberg, MD, PhD

Where do you work?

Cincinnati Children's Hospital Medical Center

What are your research interests?

Mechanisms of allergic inflammation
Eosinophilic Gastrointestinal Diseases
allerge-mRNA vaccination

What scientific achievements are you most proud of?

•    Providing the research basis, rationale (pre-clinically), proof-of-principle (clinical intervention trials) and industry coaching that contributed to the new class of anti-IL-5 therapeutics (see summary in Cell (2016:165:509)).
•    Pioneering work identifying, cloning and characterizing the first eosinophil directed chemokine, eotaxin, leading to the identification of its receptor (CCR3) and subsequent generation of multiple clinical therapeutic agents that target the eotaxin/CCR3 axis and are currently the subject of clinical trials.
•    Development of a molecular diagnostics test for EoE, the EoE Diagnostic Panel.
•    The first genome wide association analysis (GWAS) of EoE, which interrogated >550,000 genetic variants and identified a major genetic susceptibility risk allele at chromosome 5q22. This identified the importance of TSLP in EoE pathogenesis and pointed to the potential value of anti-TSLP antibody therapy, which is now being studied in clinical trials.
•    A second GWAS that interrogated >2.5 million genetic variants and identified a major genetic susceptibility risk at 2p23, that led to the discovery of why people develop tissue-specific manifestations of EGID. This work led to the identification of the enzyme calpain14 (CAPN14) as a pathogenic factor in EoE, and the potential therapeutic value of blocking its enzymatic activity; this is now being pursued.  As part of this effort, inhibitors of CAPN14 have been identified and are being improved.  Importantly, this work provided the basis for understanding the mechanism for tissue specific inflammation.
•    Elucidating the importance of IL-13 in EoE pathogenesis; his initial clinical trials demonstrated that humanized antibody against IL‐13 suppresses EoE.  These studies provided the basis for the first drug approved for EoE based on blocking IL-13 signaling.  
•    Elucidating the importance of early life environmental cues in the development of EoE, as reported by analysis of a large international cohort of EoE twins.
•    Identification of regulatory RNAs (e.g. microRNAs) in the diagnosis and pathogenesis of EoE.  This led to a focus on miR‐21, miR‐223 and miR‐375, which may serve as non-invasive biomarkers.
•    Identifying a breakdown of local barrier function in the esophagus of EoE patients and the causative role of a defect in desmoglein 1 in this process. This has now prompted a large focus on improving the impaired barrier function as a treatment of EoE. 
•    Elucidation of the key role of anti-proteases in the pathogenesis of allergic inflammation, particularly focused on impaired barrier function mediated by loss of SPINK5/7.  This included the pioneering proof-of-concept pre-clinical studies on the therapeutic value of Alpha-1-anti-trypsin for the treatment of EoE, a theory that he is now proving in patients.   
•    Identifying the allergen sensor on epithelial cells.  This sensor is mediated by assembly of the ripoptosome signaling complex, resulting in the intracellular processing and release of the key pro-atopy alarmin IL-33, a process now termed “RipIL33”.   
•    Developed a comprehensive dataset that identifies the esophagus as an immunologically active organ.
•    Developed allergen-mRNA vaccination as a platform technology for allergic diseases

Who nominated you to join the Collegium?

Bruce Bochner

What are your hobbies or what do you spend most of your time doing?

Exercising including swimming, sailing and scuba diving.

What is something you cannot live without?

Joy and pizza.

Inducted into the Collegium: October 2025