PEOPLE

Eline T. Luning Prak, MD, PhD

Associate Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
University of Pennsylvania Perelman School of Medicine

Contact Information405B Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-5768
Fax: (215) 573-6317

Email: luning@mail.med.upenn.edu

Specialty Division

Laboratory Medicine, Immunobiology and Experimental Pathology

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

Clinical Expertise

Molecular Immunology, B cell autoimmunity

Other Expertise

Pathology Resident Education

Itmat Expertise

Dr. Prak works on the genetics of B lymphocyte repertoire in autoimmunity.

Graduate Groups

Cell and Molecular Biology
Immunology

Education

A.B. (Molecular Biology), Princeton University , 1988
Ph.D. (Immunology), University of Pennsylvania, 1996
M.D. University of Pennsylvania, 1996

Specialty Certification

American Board of Pathology (Clinical Pathology), 1999

Postgraduate Training

Resident in Clinical Pathology, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 1996-1999
Postdoctoral Fellow, Department of Genetics , University of Pennsylvania School of Medicine, 1998-1999

Awards and Honors

Phi Beta Kappa, Princeton University, 1988
Stuart Mudd Award for Excellence in Microbiology/Immunology Research, 1996
Saul Winegrad Thesis Prize, Biomedical Graduate Studies, University of Pennsylvania, 1996
William Pepper Fellow in Clinical Pathology, Hospital of the University of Pennsylvania, 1998-1999
Leonard Berwick Resident Teaching Award, 1998
Outstanding Discussion Group Leader
(awarded by Penn Medical Students for Immunology section), 2001
The Peter C. Nowell Award for Excellence in Teaching, 2004
Leonard Berwick Memorial Teaching Award, 2005
Lady Barbara Colyton Prize for Autoimmune Research
Perelman School of Medicine, University of Pennsylvania, 2013
The Peter C. Nowell Teaching Award, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 2014

Memberships and Professional Organizations

College of American Pathologists, 2003 - Present
American Society of Clinical Pathology, 2004 - Present
American Association of Immunologists, 2004 - Present
Arthritis Foundation, 2004 - 2008
American Association for Investigative Pathology (ASIP), 2007 - Present
Academy of Clinical Laboratory Scientists and Physicians, 2008 - Present
Arthritis Foundation, 2010 - 2013
Institute for Translational Medicine and Therapeutics, 2010 - Present
Lupus Research Institute, 2012 - Present
Penn Institute for Immunology, 2012 - Present
German-Israel Foundation for Science, 2013 - 2013
Congressionally Directed Medical Research Program, 2013 - 2013
Arthritis Foundation, 2013 - 2013
The Dunhill Medical Trust, 2014 - Present
Adaptive Immune Receptor Repertoire (AIRR) Community, 2015 - Present
National Institute of Allergy and Infectious Disease
P01 review panel, 2016 - 2016

Web Links


Selected Publications

ImmuneDB: A system for the analysis and exploration of high-throughput adaptive immune receptor sequencing data

Rosenfeld, A., Meng, W., Luning Prak, E.T. and U. Hershberg, Bioinformatics 33(2): 292-293, 2016, PMID:27616708

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B cell development in chromosome 22q11.2 deletion syndrome

Derfalvi, B., Maurer, K., McDonald, D.M., Zackai, E., Meng, W., Luning Prak, E.T. and K.E. Sullivan., Clinical Immunology 163(): 1-9, 2016

Genetic Sharing and Heritability of Pediatric Age of Onset Autoimmune Diseases

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., Nature Communications 6(): 8442, 2015, PMID:26450413

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Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich Syndrome

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, Journal of Experimental Medicine 212(10): 1663-1677, 2015, PMID:26371186

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Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

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., Nature Medicine 21(9): 1018-1027, 2015, PMID:26301688

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Impaired receptor editing and heterozygous RAG2 mutation in a patient with systemic lupus erythematosus

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, Journal of Allergy and Clinical Immunology 135(1): 272-273, 2015, PMID:25312763

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A facile method for the site-specific, covalent attachment of full-length IgG onto nanoparticles

Hui, JZ, Zaki, AA, Cheng, Z, Popik, V., Zhang, H., Luning Prak, ET and A Tsourkas, Small in press(): , 2014

RAG2 mutants alter DSB repair pathway choice in vivo and illuminate the nature of "alternative NHEJ"

V. Gigi, S. Lewis, O. Shestova, M. Mijuskovic, L. Deriano, W. Meng, E. T. Luning Prak and D. B. Roth, Nucleic Acids Research, 2014

Persistence and selection of an expanded B cell clone in the setting of rituximab therapy for Sjögren’s syndrome

Hershberg, U., Meng, W., Zhang, B., Haff, N., St. Clair, EW, Cohen, PL, McNair, PD, Li, L, Levesque, MC and ET Luning Prak, Arthritis Research and Therapy 16(1): R51 (Epub ahead of print), 2014, PMID:24517398

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