Translational Allergic Immunopathology Unit
Michael P. O'Connell, Ph.D. (He/Him/His)
Staff Clinician/Scientist, Translational Allergic Immunopathology Unit
Major Areas of Research
- Characterizing the effects of inherited and acquired genetic variation on myeloid cell reactivity and myeloproliferation
- Define pathways critical for allergic inflammation and severe hypersensitivity reactions
The prevalence of severe allergic disease is on the rise globally; consequently, severe systemic allergic inflammation and reactions are also becoming far more frequent, representing a major public health burden causing morbidity for patients, distress for families, and substantial costs for the healthcare system. We seek to develop methods and strategies to identify individuals at with or at high risk of developing severe allergic inflammation and anaphylaxis in order to identify specific pathways leading to these phenotypes and enable the development of new therapies that can successfully limit and/or prevent these potentially devastating consequences.
Ph.D., Cell and Molecular Biology (Developmental Origins of Health and Disease), 2006
M.Sc., Biochemical Pharmacology, 2003
B.Sc., Sport and Health Sciences, minor in Psychology, 2001
Dr. O'Connell received his Ph.D. in development origins of health and disease (cell and molecular biology) from the University of Southampton School of Medicine in the United Kingdom, in collaboration with the University of Pennsylvania. He obtained postdoctoral training in the areas of Wnt5a-mediated progression of metastatic melanoma at the National Institute on Aging from 2006 to 2011. Prior to joining the Laboratory of Allergic Diseases in 2014, Dr. O'Connell was a staff scientist at the Wistar Institute, Philadelphia, from 2011 to 2014, where he investigated mechanisms of drug resistance in cancer.
Dr. O’Connell joined the Laboratory of Allergic Diseases from the Wistar Institute in 2015. Working in the Genetics and Pathology of Allergy Section, he has investigated endothelial cell-driven mechanisms promoting atopy. He joined the Translational Allergic Immunopathology Unit in 2019 bringing with him expertise in molecular biology and cancer and is leading efforts to understand how inherited and acquired genetic variation in endothelial and myeloid cells can promote severe allergic reactions and myeloproliferation.
Konnikova L, Robinson TO, Owings AH, Shirley JF, Davis E, Tang Y, Wall S, Li J, Hasan MH, Gharaibeh RZ, Mendoza Alvarez LB, Ryan LK, Doty A, Chovanec JF, O'Connell MP, Grunes DE, Daley WP, Mayer E, Chang L, Liu J, Snapper SB, Milner JD, Glover SC, Lyons JJ. Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia. J Allergy Clin Immunol. 2021 Sep;148(3):813-821.e7.
Lyons JJ, Chovanec J, O'Connell MP, Liu Y, Šelb J, Zanotti R, Bai Y, Kim J, Le QT, DiMaggio T, Schwartz LB, Komarow HD, Rijavec M, Carter MC, Milner JD, Bonadonna P, Metcalfe DD, Korošec P. Heritable risk for severe anaphylaxis associated with increased α-tryptase-encoding germline copy number at TPSAB1. J Allergy Clin Immunol. 2021 Feb;147(2):622-632.
O'Connell MP, Lyons JJ. Hymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemia. Curr Opin Allergy Clin Immunol. 2020 Oct;20(5):431-437.
Zhang Y, Ma CA, Lawrence MG, Break TJ, O'Connell MP, Lyons JJ, López DB, Barber JS, Zhao Y, Barber DL, Freeman AF, Holland SM, Lionakis MS, Milner JD. PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients. J Exp Med. 2017 Sep 4;214(9):2523-2533.
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.
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.