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John Thomas Schroeder, Ph.D.
Director, Genetic Research Programs (BGRF)
Associate Professor of Medicine
Research Interests: Mechanisms regulating cytokine/mediator release by IgE receptor-bearing cells; Innate vs. adaptive immunity in regulating cellular responses in IgE receptor positive cells ...read more
John T. Schroeder, Ph.D. is currently Associate Professor of Medicine at The Johns Hopkins University School of Medicine in Baltimore, Maryland. His experience in working with basophils actually began in graduate school where his dissertation studies were instrumental in describing basophils as a source of IL-4 (and now IL-13). He continued this work during his post-doctoral fellowship at The Johns Hopkins Asthma and Allergy Center under the mentorship of Dr. Lawrence M. Lichtenstein, M.D., Ph.D. He then joined the Division of Allergy and Clinical Immunology of the Department of Medicine in 1995 after his fellowship and has been continuously funded by various NIH institute (NIAID, NHLBI) grants and pharmaceutical contracts. He is a member of the American Academy of Allergy, Asthma and Immunology and the Leukocyte Biology Society. He has served ~10 years as an ad-hoc reviewer on various NIH Study Sections, including the Hypersensitivity, Autoimmunity and Immunology (HAI) and Innate Immunity and Inflammation (III) review groups. He has also served on the Editorial Board for Allergy and is currently a peer-reviewer for many leading allergy and immunology journals. He is an author of more than 75 peer-reviewed publications, reviews and book chapters. He lectures on a variety of topics regarding basophils, mast cells, dendritic cells, & cytokines in allergic inflammation, and is also a lecturer within the Graduate Immunology program within the School of Medicine at Johns Hopkins University. Dr. Schroeder has either trained and/or mentor numerous clinical and research postdoctoral fellows, visiting scientists, and students (graduate and undergraduate).
- Director, Genetic Research Programs (BGRF)
- Associate Professor of Medicine
Centers & Institutes
- Ph.D., East Carolina University (North Carolina) (1993)
Johns Hopkins University School of Medicine, Baltimore, MD, 1995, Research Postdoctoral Fellowship, Division of Clinical Immunology
Research & Publications
This laboratory during the last two decades has focused on understanding the role human basophils and mast cells play in allergic reactions, as it relates not only to their secretion of potent inflammatory mediators (e.g. histamine and leukotriene C4), but also to their production of pro-inflammatory cytokines. Particular emphasis has been on studies investigating the parameters and mechanisms underlying the production of IL-4 and IL-13 by basophils, as these two cytokines are known to play a critical role in the pathogenesis of allergic disease. As a result, this laboratory has played a significant role in characterizing the basophil as a major source of these "Th2-like" cytokines, so named for their initial description in a subclass of T helper lymphocytes. We first demonstrated this response in vitro using basophils isolated from blood and under conditions involving IgE-dependent and IgE-independent activation. We have also extended these observations to clinically relevant disease by showing that basophils infiltrating the airways following allergen challenge are also a primary source of these cytokines. Overall, the implications are that basophils, by secreting all of the major products linked to allergic inflammation (i.e. IL-4, IL-13, histamine and LTC4), orchestrate both immunomodulatory and effecter roles in allergic disease. Consequently, this laboratory has also played a leading role in characterizing these responses in subjects suffering from diverse types of allergic disease, ranging from asthma to food allergy.
During the last decade this laboratory has also expanded its research interests to include dendritic cell (DC) biology, after observing unique phenotypic and functional similarities between basophils and a particular dendritic cell (DC) subtype referred to as the plasmacytoid DC (pDC). For example, pDCs express a variant of FcεRI (ag2), which enables these cells to bind IgE immunoglobulin with high affinity, much like basophils and mast cells. Importantly, our work has shown evidence for the existence of a unique counter-regulatory axis between FcεRI and a specific innate immune receptor (e.g. TLR9) co-expressed by pDC. In vitro studies show that activation of pDCs through FcεRI (as mediated by allergen) suppresses their capacity to respond to TLR9 agonists. In contrast, if pDC are first activated via TLR9 agonists, then they down-regulate FcεRI. Overall, this mechanism may very well explain why pDC from allergic subjects are impaired in responding to TLR9 agonists, which are known to activate substances [e.g. interferon (IFN)-alpha] that can suppress the Th2 responses linked to allergic inflammation. Likewise, the clinical efficacy seen in treating allergic disease with therapeutics targeting TLR9 (e.g. so-called CpG-based compounds) may result from their capacity to counter-regulate FcεRI responses in the pDC subtype.
Finally, this laboratory has long utilized human cells rather than cell lines in order to address the parameters, signal transduction, and pharmacological aspects underlying clinically relevant basophil, mast cell, and DC responses. As a result, this laboratory has established protocols for rapidly isolating relatively large numbers of these cell types at high purity from human blood, and for growing culture-derived mast cells from human progenitor cells. A variety of assays and techniques are also in place for concurrently detecting cytokines and mediators following a wide range of stimuli. These have thus facilitated the in vitro pharmacologic testing of numerous anti-allergic drugs for inhibitory activity on basophil, mast cell, and DC activation.
Technology Expertise Keywordsisolation of rare human leukocytes, immune-based assays
Academic Affiliations & Courses
Graduate Program AffiliationAllergy Lecture for the Graduate Immunology Program (2012-present) Orientation Confrences to the incoming Fellows (1996-present)
Activities & Honors
- American Academy of Allergy, Asthma and Immunology
- Leukocyte Biology Society
- Editorial Board, Allergy