Eline Tjetske Luning Prak

faculty photo
Associate Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
405B Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-5768
Fax: (215 ) 573-6317
A.B. (Molecular Biology)
Princeton University , 1988.
University of Pennsylvania, 1996.
Ph.D. (Immunology)
University of Pennsylvania, 1996.
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Description of Research Expertise

Research Interests
Dr. Luning Prak works on the genetics of the antibody repertoire in autoimmunity.

Key words: antibody, V(D)J recombination, receptor editing, immunoglobulin, autoimmunity, antibody repertoire, lupus, diabetes

Description of Research
B cells produce antibodies and are important for innate and adaptive immunity. B cells that are improperly regulated can also cause or contribute to autoimmunity. Our major research interest is in defining B cell tolerance checkpoint defects in mouse models and patients with autoimmune diseases. B cells with a functional antibody can undergo further rearrangement, a process termed receptor editing. Receptor editing is a significant mechanism for central (early) B cell tolerance. Recent work from our lab demonstrates lower levels of editing in approximately 30% of patients with lupus and 30% of patients with type 1 diabetes, as well as in mouse models of these diseases. These findings suggest that a significant proportion of patients with different autoimmune diseases have defects in early B cell tolerance, and may provide insights into which patients will respond best to B cell targeted therapy.

In collaboration with our colleagues in Rheumatology, Transplant Surgery and Endocrinology, we are analyzing B cell subsets in humans with lupus, Sjogren's Syndrome and in non-human primates (NHPs) with drug-induced diabetes. We observe a direct correlation between the length of B cell depletion and improvement in disease (lower disease activity score for SLE, longer period of tolerance to allogeneic pancreatic islet transplants in the non-human primates). Of great interest in these studies are the shifts that occur in the B cell repertoire over time. A repertoire in which immature B cells dominate may be more susceptible to tolerance induction. We are currently testing this idea in patients with type 1 diabetes who are receiving pancreatic islet transplants as part of a multi-center Clinical Islet Transplantation consortium.

We also pursue a number of basic research projects involving mice. These include studying the frequency, timing and pathways of receptor editing rearrangements in immunoglobulin knock-in mice, mapping genetic causes for tolerance checkpoints and analyzing the antibody repertoire following manipulations of the B cell compartment. Rotation and thesis projects are available in basic as well as human translational immunology pertaining to B cell autoimmunity.

Rotation Projects
Please come visit the lab to discuss rotation projects in any of the areas discussed above. Projects will be tailored to the background and interests of the student.

Lab personnel:
Sara Smith, graduate student
Debora Sekiguchi, MD, PhD, research fellow
Wenzhao Meng, PhD, postdoctoral fellow
Yang Zhu Du, Ph.D., research specialist
Noah Goodman, research specialist
Emily Xue, Penn undergraduate
Yang Liu, Carnegie Mellon undergraduate

Description of Clinical Expertise

Molecular Immunology, B cell autoimmunity

Description of Other Expertise

Pathology Resident Education

Selected Publications

Meng, W., Zhang, B., Schwartz, GW, Rosenfeld, AM, Ren, D., Thome, J JC, Carpenter, DJ, Matsuoka, N., Lerner, H., Friedman, A.L., Granot, T., Farber, D.L., Shlomchik, M.J., Hershberg, U. and E.T. Luning Prak.: An atlas of B cell clonal distribution in the human body. Nature Biotechnology 35(9): 879-884, September 2017.

Rosenfeld, A., Meng, W., Luning Prak, E.T. and U. Hershberg: ImmuneDB: A system for the analysis and exploration of high-throughput adaptive immune receptor sequencing data. Bioinformatics 33(2): 292-293, January 2017.

Hanley, P., Sutter, J.A., Goodman, N.G., Du, Y., Sekiguchi, D.R., Meng, W., Rickels, M.R., Naji, A. and E.T. Luning Prak.: Circulating B cells in type 1 diabetics exhibit fewer maturation-associated phenotypes. Clinical Immunology in press, 2017.

Derfalvi, B., Maurer, K., McDonald, D.M., Zackai, E., Meng, W., Luning Prak, E.T. and K.E. Sullivan.: B cell development in chromosome 22q11.2 deletion syndrome. Clinical Immunology 163: 1-9, 2016.

Zhang, B., Meng, W., Luning Prak, E.T. and U. Hershberg: Discrimination of germline V genes at different sequencing lengths and mutational burdens: a new tool for identifying and evaluating the reliability of V gene assignment. J. Immunol. Methods 427: 105-116, December 2015.

Li, Y.R., Zhao, S., Mohebnasab, M., Li, J., Bradfield, J., Steel, L., Abrams, D., Kobie, J., Mentch, F., Glessner, J., Guo, Y., Wei, Z., Cardinale, C., Bakay, M., Connoly, J., Li, D., Maggadottir, M., Thomas, K.A., Qiu, H., Chiavacci, R., Kim, C., Wang, F., Snyder, J., Flato, B., Forre, O., Denson, L., Thompson, S.D., Becker, M., Guthery, S.L., Latiano, A., Perez, E., Resnick, E., Strisciuglio, C., Staiano, A., Miele, E., Silverberg, M., Lie, B.A., Punaro, M., Russell, R., Wilson, D., Dubinsky, M.C., Monos, D.S., Annese, V., Munro, J., Wise, C., Chapel, H., Cunningham-Rundles, C., Orange, J., Behrens, E.M., Sullivan, K., Kugathasan, S., Griffiths, A., Satsangi, J., Grant, S., Sleiman, P., Finkel, T., Polychronakos, C., Baldassano, R.N., Luning Prak, E.T., Ellis, J., Li, H., Keating, B.J. and H. Hakonarson.: Genetic Sharing and Heritability of Pediatric Age of Onset Autoimmune Diseases. Nature Communications 6: 8442, October 2015.

Kolhatkar, N.S., Brahmandam, A., Thouvenel, C., Becker-Herman, S., Jacobs, H.M., Schwartz, M.A., Khim, S., Panigrahi, A.K., Luning Prak, E.T., Thrasher, A.J., Notarangelo, L.D., Candotti, F., Torgerson, T.R., Sanz, I.A. and D. J. Rawlings: Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich Syndrome. Journal of Experimental Medicine 212(10): 1663-1677, September 2015.

Li, Y.R., Li, J., Zhao, S.D., Bradfield, J.P., Mentch, F.D., Maggadottir, S.M., Hou, C., Abrams, D.J., Chang, D., Gao, F., Guo, Y., Wei, Z., Connolly, J.J., Cardinale, C.J., Bakay, M., Glessner, J.T., Li, D., Kao, C., Thomas, K.A., Qiu, H., Chiavacci, R.M., Kim, C.E., Wang, F., Snyder, J., Richie, M.D., Flato, B., Forre, O., Denson, L.A., Thompson, S.D., Beckerk, M.L., Guthery, S.L., Latiano, A., Perez, E., Resnick, E., Russell, R.K., Wilson, D.C., Silverberg, M.S., Annese, V., Lie, B.A., Punaro, M., Dubinsky, M.C., Monos, D.S., Strisciuglio, C., Staiano, A., Miele, E., Kugathasan, S., Ellis, J.A., Munro, J.E., Sullivan, K.E., Wise, C., Chapel, H., Cunningham-Rundles, C., Grant, S.F.A., Orange, J.S., Sleiman, P.M.A., Behrens, E.M., Griffiths, A.M., Satsangi, J., Finkel, T.H., Keinan, A., Luning Prak, E.T., Polychronakos, C., Baldassano, R.N., Li, H., Keating, B.J. and H. Hakonarson.: Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases. Nature Medicine 21(9): 1018-1027, September 2015.

Walter, J.E., Lo, M., Kis-Toth, K., Tirosh, I., Frugoni, F., Lee, Y.N., Abraham, R.S., Chen, K., Pillai, S., Dunham, J., Tsokos, G., Luning Prak*, E.T. and L.D. Notarengelo *co-corresponding author: Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus. Journal of Allergy and Clinical Immunology 135(1): 272-273, January 2015.

Hui, JZ, Zaki, AA, Cheng, Z, Popik, V., Zhang, H., Luning Prak, ET and A Tsourkas: A facile method for the site-specific, covalent attachment of full-length IgG onto nanoparticles. Small in press, April 2014.

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Last updated: 10/15/2017
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