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.
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 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.
Desai, A., Sowerwine, K., Liu, Y., Lawrence, M.G., O’Connell, M.P., Chovanec, J., Hsu, A.P., Boris, L., Jones, N., Zerbe, C., Wisch, L., Maric, I., Lee, R.C., Gilfillan, A., Stone, K.D., Milner, J.D., Holland, S.M., Metcalfe, D.D., Lyons, J.J. GATA2-deficient mast cells limit type I hypersensitivity reactions in humans. J Allergy Clin Immunol. 2019 May 15.
Lyons, J.J., Liu, Y., Ma, C., Yu, X., O'Connell, M.P., Lawrence, M., Zhang, Y., Karpe, K., Zhao, M., Siegel, A., Stone, K.D., Nelson, C., Jones, N., Dimaggio, T., Darnell, D., Mendoza-Caamal, E., Orozco, L., Hughes, J., McElwee, J., Hohman, R., Frischmeyer-Guerrerio, P., Rothenberg, M., Freeman, A., Holland, S., and Milner, J.D. ERBIN deficiency links STAT3 and TGF-β pathway defects with atopy in humans. J Exp Med. 2017 Mar 6.
Lyons, J.J., Yu, X., Hughes, J.D., Le, Q.T., Jamil, A., Bai, Y., Ho, N., Zhao, M., Liu, Y., O'Connell, M.P., Trivedi, N.N., Nelson, C., DiMaggio, T., Jones, N., Matthews, H., Lewis, K.L., Oler, A.J., Carlson, R.J., Arkwright, P.D., Hong, C., Agama, S., Wilson, T.M., Tucker, S., Zhang, Y., McElwee, J.J., Pao, M., Glover, S.C., Rothenberg, M.E., Hohman, R.J., Stone, K.D., Caughey, G.H., Heller, T., Metcalfe, D.D., Biesecker, L.G., Schwartz, L.B., Milner, J.D. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016 Dec.
Kaur, A., Webster, M.R., Marchbank, K., Behera, R., Ndoye, A., Kugell III, C.H., Dang, V.M., Appleton, J., O’Connell, M.P., Cheng, P., Valiga, A.A., Morissette, R., McDonnell, N.B., Ferrucci, L., Kossenkov, A.V., Meeth, K., Tang, H., Yin, X., Wood III, W.H., Lehrmann, E., Becker, K.G., Flaherty, K.T., Frederick, D.T., Wargo, J.A., Cooper, Z.A., Tetzlaff, M.T., Hudgens, C., Aird, K.M., Zhang, R., Xu, X., Liu, Q., Bartlett, E., Karakousis, G., Eroglu, Z., Lo, R.S., Chan, M., Menzies, A.M., Long, G.V., Johnson, D.B., Sosman, J., Schilling, B., Schadendorf, D., Speicher, D.W., Bosenberg, M., Ribas, A., and Weeraratna, A.T. sFRP2 in the aged microenvironment drives melanoma metastasis and resistance to targeted therapy. Nature. 2016 Apr 14.
O’Connell, M.P.*, Hox, V.*, Lyons, J.J., Sackstein, P., Dimaggio, T., Jones, N., Nelson, C., Boehm, M., Holland, S.M., Freeman, A.F., Tweardy, D.J., Olivera, A., Metcalfe, D.D., Milner, J.D. Diminution of signal transducer and activator of transcription 3 signaling inhibits vascular permeability and anaphylaxis. J Allergy Clin Immunol. 2016 Jul;138(1):187-99. doi: 10.1016/j.jaci.2015.11.024. * Co-first author
O’Connell M.P., Marchbank K., Webster M.R., Valiga A., Kaur A.A., Vultur A.M., Li L., Herlyn M., Villanueva J., Liu Q., Yin X., Widura S., Nelson J., Ruiz N., Camilli T.C., Indig F.E., Flaherty K.T, Wargo J.A., Frederick D.T.,. Cooper Z.A., Nair S., Amaravadi R.K., Schuchter L.M., Karakousis G., Xu W., Xu X., Weeraratna A.T. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Discov. 2013 Dec;3(12):1378-93.