Major Areas of Research
- Characterize inherited or acquired genetic variants leading to severe allergic inflammation and reactions in order to dissect their pathogenesis
- Define immunogenetic and metabolic mechanisms regulating myeloid cell proliferation and reactivity in allergic diseases
- Develop novel targeted therapeutic approaches for individuals with severe allergic inflammation and reactivity
The central goal of the Translational Allergic Immunopathology Unit (TAIU) is to identify mechanisms and pathways critical to allergic hypersensitivity that can be targeted in order to conduct first in human clinical trials that prevent severe reactions and inflammation. In order to accomplish this translational research objective, the TAIU has active clinical and laboratory research programs, employing a model of bed-to-bench and back to the bedside.
The principle approach we employ for identification of therapeutic targets is to identify and characterize inherited, or acquired, genetic disorders and traits that promote severe allergic inflammation and reactions. From those identified to date, two major areas of current focus are: 1) characterizing pathways leading to increased mast cell hyperactivity and anaphylaxis in individuals with hereditary alpha tryptasemia (HaT) – a common genetic trait resulting from increased TPSAB1 copy number, and; 2) identifying the mechanisms underlying severe eosinophilic and mast cell-mediated inflammation and reactivity in patients with Phosphoglucomutase-3 (PGM3) deficiency, an autosomal recessive congenital disorder of glycosylation.
These projects are facilitated by two active clinical protocols that Dr. Lyons directs as the Principal Investigator, as well as his integral involvement as an Associate Investigator on six clinical protocols within NIAID and NHGRI designed to study: mastocytosis, anaphylaxis, Hyper-IgE syndromes, primary immunodeficiency disorders, population genetics, and glycosylation disorders. Dr. Lyons is also frequently consulted by the Undiagnosed Diseases Program and has jointly recruited patients with this service. Once causes for the observed phenotypes are genetically defined, strategies must be devised in order to translate these findings back into clinical practice. To accomplish this, the TAIU has developed a number of in vitro and in vivo model systems and continues to use these in order to devise interventional protocols to test the efficacy of new interventions to prevent allergic inflammation and hypersensitivity.
Read more about Dr. Lyons’s work in NIH Scientists Uncover Genetic Explanation for Frustrating Syndrome.
Jonathan Lyons received his undergraduate education at Pomona College and Jesus College, Cambridge, United Kingdom, where he spent two terms. He graduated with a B.A. in chemistry from Pomona College in 2003 and received an M.D. from the University of Southern California in 2007. Dr. Lyons completed residency training in internal medicine at the University of California, San Diego, in 2010, and served as a chief medical resident in 2011. He concluded his formal medical training in 2014 at NIAID as a clinical fellow in allergy and immunology. Following completion of a fellowship, he was selected for the NIAID Transition Program in Clinical Research and served as an assistant clinical investigator in the Laboratory of Allergic Diseases (LAD) until 2018. Dr. Lyons is now chief of the Translational Allergic Immunopathology Unit in LAD.
In 2015 Dr. Lyons received the ARTrust/The Mastocytosis Society Research Award in Mastocytosis and/or Mast Cell Activation Syndrome. Dr. Lyons received NIAID Merit Awards in 2016 and 2017 for his work related to the identification and characterization of hereditary alpha tryptasemia and was named a Lasker Scholar in 2018.
Dr. Lyons was also featured in a story in the NIH Catalyst , The Jugglers.
Postdoctoral fellows interested in joining the TAIU, please email Dr. Lyons and include a current CV or Biosketch.
Sabato V, Chovanec J, Faber M, Milner JD, Ebo D, Lyons JJ. First Identification of an Inherited TPSAB1 Quintuplication in a Patient with Clonal Mast Cell Disease. J Clin Immunol. 2018 May;38(4):457-459.
Lyons JJ, Stotz SC, Chovanec J, Liu Y, Lewis KL, Nelson C, DiMaggio T, Jones N, Stone KD, Sung H, Biesecker LG, Colicos MA, Milner JD. A common haplotype containing functional CACNA1H variants is frequently coinherited with increased TPSAB1 copy number. Genet Med. 2018 Apr;20(5):503-512.
Carlson RJ, Bond MR, Hutchins S, Brown Y, Wolfe LA, Lam C, Nelson C, DiMaggio T, Jones N, Rosenzweig SD, Stone KD, Freeman AF, Holland SM, Hanover JA, Milner JD, Lyons JJ. Detection of phosphoglucomutase-3 deficiency by lectin-based flow cytometry. J Allergy Clin Immunol. 2017; 140(1):291-294.e4.
Lyons JJ, Liu Y, Ma CA, Yu X, O'Connell MP, Lawrence MG, Zhang Y, Karpe K, Zhao M, Siegel AM, Stone KD, Nelson C, Jones N, DiMaggio T, Darnell DN, Mendoza-Caamal E, Orozco L, Hughes JD, McElwee J, Hohman RJ, Frischmeyer-Guerrerio PA, Rothenberg ME, Freeman AF, Holland SM, Milner JD. ERBIN deficiency links STAT3 and TGF-β pathway defects with atopy in humans. J Exp Med. 2017 Mar 6;214(3):669-680.
Desai A, Sowerwine K, Liu Y, Lawrence MG, Chovanec J, Hsu AP, O’Connell MP, Kim J, Boris L, Jones N, Wisch L, Eisch RR, Carter MC, Komarow HD, Zerbe C, Milner JD, Maric I, Sun X, Lee CR, Tunc I, Pirooznia M, Stone KD, Holland SM, Metcalfe DD, Lyons JJ. GATA2-deficient mast cells limit IgE-mediated immediate hypersensitivity reactions in humans. J Allergy Clin Immunol. 2019 Aug;144(2):613-617.
Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, Ho N, Zhao M, Liu Y, O'Connell MP, Trivedi NN, Nelson C, DiMaggio T, Jones N, Matthews H, Lewis KL, Oler AJ, Carlson RJ, Arkwright PD, Hong C, Agama S, Wilson TM, Tucker S, Zhang Y, McElwee JJ, Pao M, Glover SC, Rothenberg ME, Hohman RJ, Stone KD, Caughey GH, Heller T, Metcalfe DD, Biesecker LG, Schwartz LB, Milner JD. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016 Dec;48(12):1564-1569.
Individuals interested in participating in these clinical trials should contact Sheryce Lassiter