This contract program supports the development and refinement of animal models and animal replacement technologies and provides in vivo and complex human cell-based in vitro model preclinical testing services, ranging from screening and proof-of-concept to GLP efficacy studies.
Plague, caused by the bacterium Yersinia pestis, is a disease that affects humans and other mammals. People typically get infected after being bitten by a rodent flea that is carrying the bacterium or by handling a plague-infected animal. Although the disease killed millions in Europe during the Middle Ages, antibiotics effectively treat plague today. Without prompt treatment, plague can cause serious illness or death. Human plague infections continue to occur in the western United States, but significantly more cases occur in parts of Africa and Asia.
Plague is a category A pathogen which are those organisms/biological agents that pose the highest risk to national security and public health because they can be easily disseminated or transmitted from person to person, result in high mortality rates and have the potential for major public health impact, might cause public panic and social disruption, and require special action for public health preparedness.
NIAID conducts and supports research on the diagnosis, prevention, and treatment of infections caused by microbes, including those that have the potential for use as biological weapons. The research program to address biodefense includes both short- and long-term studies targeted at designing, developing, evaluating, and approving specific tools (diagnostics, drugs, and vaccines) needed to defend against possible bioterrorist-caused disease outbreaks.
To learn about risk factors for plague and current prevention and treatment strategies visit the MedlinePlus plague site.
NIAID is working with the U.S. Department of Defense, the Centers for Disease Control and Prevention, and the U.S. Department of Energy to develop a vaccine that protects against inhalationally acquired pneumonic plague
NIAID-funded scientists have developed a rapid diagnostic test for pneumonic plague that can be used in most hospitals. This will allow healthcare providers to quickly identify and isolate the pneumonic plague patient from other patients and enable healthcare providers to use appropriate precautions to protect themselves.
NIAID is working with the U.S. Department of Defense, the Centers for Disease Control and Prevention, and the U.S. Department of Energy to develop promising antibiotics and intervention strategies to treat and prevent plague infection.
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.
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.
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.