Neurobiology and Pain Therapeutics, DIR
NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 49 ROOM 1C20
49 CENTER DR
BETHESDA MD 20892
Phone: (301) 402-0778
Fax: (301) 402-0667
E-mail:
burbelop@.nidcr.nih.gov
We have developed a novel antibody profiling technology, Luciferase Immunoprecipitation Systems (LIPS), which harnesses light-emitting recombinant proteins for quantitatively measuring patient antibody titers to any antigenic target. The simplicity of the LIPS format enables us to quickly clone, express and test antigenic targets and makes the technology an ideal system for assessing new disease biomarkers in infection, autoimmunity, cancer, and other conditions. My primary interest is to use LIPS in two areas: (i) understanding humoral responses to known and emerging pathogens, and (ii) biomarker discovery. One of the most productive areas of our group has been antibody profiling of known viral, bacterial, filarial, and other pathogens. Quantitative measurement of patient humoral responses by LIPS against these pathogens provides objective information for diagnosis, monitoring of illnesses and possible treatment selection. We have used LIPS to profile patients’ global antibody responses to a pathogen’s entire proteome such as all the proteins from HIV-1 and HCV and partial proteomes of KSHV and EBV. This approach allows us to identify new, previously undescribed antigenic targets that may be superior targets for vaccine development and other therapies than those currently being explored. LIPS analysis can also be used to identify antibody responses against newly identified pathogens with potential causative roles in human disease. In addition to infectious agents, we have developed some of the best immunoassays for detecting antibodies to human autoantigens. These LIPS-based tests can be used to diagnose and even predict some conditions and may lead to more highly targeted disease management. For example, in Sjögren’s syndrome, we identified patterns of autoantibodies associated with neurological, thyroid and gastric complications. Overall, these patient-specific, quantitative antibody profiles may provide insight into human health and disease that cannot be assessed by existing technologies.
Recent Publications
Burbelo, P.D., Seam, N., Groot, S., Ching, K.H., Han, B.L., Meduri, G.U., Iadarola, M.J., and Suffredini, A.F. Rapid induction of autoantibodies during ARDS and Septic shock. J. of Translational Medicine (in press, 2010).
Burbelo, P.D., Browne, S. K, Sampaio, E.P., Giaccone, G., Zaman, R., Kristostuyan, E., Rajan, A., Ding L., Ching, K.H., Berman, A., Hsu, A., Klimavicz, C.M., Iadarola, M.J. and Holland, S.M. Anti-cytokine autoantibodies are associated with opportunistic infection in thymic neoplasia. Blood (in press, 2010).
Burbelo, P.D., Kovacs, J.A., Ching, K.H., Issa, A.T., Iadarola, M.J., Schlaak, J., Masur, H., Polis, M.A. and Kottilil, S. Proteome-wide Anti-HCV and Anti-HIV Antibody Profiling for Predicting and Monitoring Response to HCV Treatment in HIV Co-infected Patients. J. Infectious Diseases 202 (6):894-898, 2010.
Burbelo, P.D., Ching, K.H., Hahn, B.L., Klimavicz, C.M. and Iadarola, M.J. Synthetic biology for translational research. American Journal of Translational Research 2(4):381-389, 2010.
Burbelo, P.D., Ching, K.H., Bush, E.R., Hahn, B.L. and Iadarola, M.J. Antibody profiling technologies for studying humoral responses to infectious agents. Expert Review of Vaccines 9(6):567-578, 2010.
Burbelo, P.D., Issa, A.T., Ching, K.H., Cohen, J.I., Iadarola, M.J., and Marques, A. Simple, quantitative, and highly sensitive antibody detection for Lyme disease. Clinical and Vaccine Immunology 17:904-909, 2010.
Burbelo, P.D., Issa, A.T., Ching, K.H., Wyvill, K., Little, R.F., Iadarola, M.J., Kovacs, J.A., and Yarchoan, R. Distinct profiles of antibodies to Kaposi Sarcoma-associated Herpesvirus antigens in Kaposi Sarcoma, Multicentric Castlemen’s Disease and Primary effusion lymphoma. J. Infectious Diseases 201(12):1919-1922, 2010.
Burbelo, P.D., Ching, K.H., Hahn, B.L., Bush, E.R., Issa, A.T., Reeves, W. and Iadarola, M. Extraordinary antigenicity of conformational epitopes within the human Ro52 protein. American Journal of Translational Research 2(2):145-155, 2010.
Burbelo, P.D., Hirai, H., Issa, A.T., Lernmark, A., Ivarsson, S-A., Notkins, A. L. and Iadarola, M.J. Comparison of radioimmunoprecipitation with luciferase immunoprecipitation for autoantibodies to GAD65 and IA-2ß. Diabetes Care 33(4): 754-756, 2010.
Burbelo, P.D., Issa, A.T., Ching, K.H., Loftus, C., Li, Y., Satoh, M., Reeves, W., and Iadarola, M.J. Rapid Serological Detection of Autoantibodies Associated with Sjögren’s Syndrome. J. of Translational Medicine. 7: 83, 2009
Burbelo, P.D., Ching, K.H., Klimavicz, C.M. and Iadarola, M.J. Antibody Profiling by Luciferase Immunoprecipitation Systems (LIPS). J. of Visualized Experiments 32, http://www.jove.com/index/%20Details.stp?ID=1549, doi:10.3791/1549.
Burbelo, P.D., Leahy, H.P., Issa, A.T., Groot, S., Baraniuk, J.N., Nikolov, N., Illei, G., and Iadarola, M.J. Sensitive and robust luminescent detection of anti-La and other autoantibodies in Sjögren’s syndrome. Autoimmunity, 42 (6): 515-524, 2009.
Sashihara, J., Burbelo, P.D., Savoldo, B., Pierson, T.C., and Cohen, J.I.. Human Plasma Antibody Titers to Epstein-Barr Virus (EBV) gp350 Correlate with Neutralization of Infectivity Better than Antibody Titers to EBV gp42 Using a Rapid Flow Cytometry-Based EBV Neutralization Assay. Virology, 391: 249-256, 2009.
Beigel, J.H., Voell, J., Huang, C., Burbelo, P.D., and Lane, C.H. Safety and Immunogenicity of Multiple and Higher Doses of an Inactivated Influenza A/H5N1 Vaccine. J. Infectious Diseases, 200 (4):501-508, 2009.
Burbelo, P.D., Leahy, H.P., Iadarola, M.J. and Nutman, T.B. A Four Antigen Mixture for the Rapid Assessment of Onchocerca volvulus Infection. PLOS NTD, 3(5):e438, 2009.
Burbelo, P.D., Issa, A.T, Ching, K.H., Leahy, H.P., Exner, M., Drew, W.L., Alter, H.J. and Iadarola, M.J. Highly quantitative serological detection of anti-cytomegalovirus (CMV) antibodies. Virology Journal, 6 (1):45, 2009.
Burbelo, P.D., Leahy, H.P., Groot, S., Bishop, L.R., Miley, Iadarola, M.J., Whitby, D., and Kovacs, J.A. A Four Antigen Mixture Containing V-Cyclin for Serological Screening of Human Herpesvirus-8 (HHV-8) Infection. Clinical and Vaccine Immunology, 16: 621-627, 2009.
Burbelo, P.D., Hoshino, Y., Leahy, H.P., Krogmann, T., Hornung, R.L., Iadarola, M.J., and Cohen J. I. Serological Diagnosis of Human HSV-1 and HSV-2 Infection by Luciferase Immunoprecipitation Systems (LIPS) Assay. Clin. Vaccine Immunol. 16: 366-371, 2009.