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Eline Tjetske Luning Prak, MD, PhD

Eline Tjetske Luning Prak, MD, PhD

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

Hershberg, U., Meng, W., Zhang, B., Haff, N., St. Clair, EW, Cohen, PL, McNair, PD, Li, L, Levesque, MC and ET Luning Prak: Persistence and selection of an expanded B cell clone in the setting of rituximab therapy for Sjögren’s syndrome. Arthritis Research and Therapy. Peter Lipsky (eds.). BioMed Central, 16(1): R51 (Epub ahead of print), February 2014.

Radic, M., Weigert, M., Khan, S.N., Han, J., Kalinina, O. and E.T. Luning Prak: Antibodies that bind complex glycosaminoglycans accumulate in the golgi. Proc Natl Acad Sci USA 110(29): 11958-63, July 2013.

Rickels, M., Liu, C., Shlansky-Goldberg, R., Soleimanpour, S., Vivek, K., Kamoun, M., Min, Z., Markmann, E., Palangian, M., Dalton-Bakes, C., Fuller, C., Chiou, A., Barker, C., Luning Prak, E. and A. Naji: Improvement in beta-cell secretory capacity following human islet transplantation according to the CIT07 protocol. Diabetes 62(8), April 2013 Notes: doi: 10.2337/db12-1802.

Chu, C.S., Boyer, J.D., Jawad, A., McDonald, K., Rogers, W.T., Luning Prak, E.T. and K.E. Sullivan: Immunologic consequences of chemotherapy for ovarian cancer: impaired responses to the influenza vaccine. Vaccine 31: 5435-5442, 2013.

St. Clair, E.W., Levesque, M.C., Luning Prak, E.T., Vivino, F.B., Alappatt, C.J., Spychala, M.E., Wedgwood, J., McNamara, J., Moser Sivils, K.L., Fisher, L. and P. Cohen: Rituximab Therapy for Primary Sjogren's Syndrome: An Open-Label Clinical Trial and Mechanistic Analysis. Arthritis and Rheumatism 65(4): 1097-1106, 2013.

Andrews, S., Zhang, Q., Lim, S., Li, L., Lee, J-H, Zheng, N. Y., Huang, M., Taylor, W., Farris, A. D., Ni, D., Meng, W., Luning Prak, E. T. and P. Wilson: Global analysis of B cell selection using an immunoglobulin light chain-mediated model of autoreactivity. Journal of Experimental Medicine 210(1): 125-142, 2013.

Benichou, J., Glanville, J., Luning Prak, E.T., Azran, R., Kuo, T.C., Pons, J., Desmarais, C., Tsaban, L. and Y. Louzoun: DH reading frame usage in the expressed human antibody repertoire is selected based upon amino acid content. J. Immunol. 190(11): 5567-5577, 2013.

Nickerson, K.M., Christensen, S.R., Cullen, J.L., Meng, W., Luning Prak, E. T. and M. J. Shlomchik.: TLR9 Promotes Tolerance by Restricting Survival of Anergic Anti-DNA B Cells Yet is Also Required for Their Activation. J. Immunol. 190(4): 1447-1456, 2013.

Grupp, S.A., Luning Prak, E.T., Boyer, J., McDonald, K.R., Shusterman, S., Thompson, E., Callahan, C., Jawad, A.F., Levine, B.L., June, C.H. and K.E. Sullivan: Adoptive transfer of autologous T cells improves T cell repertoire diversity and long-term B-cell function in pediatric patients with neuroblastoma. Clinical Cancer Research 18(24): 6732-6741, October 2012.

Eisenberg, R.A., Jawad, A.F., Boyer, J., Maurer, K., McDonald, K., Luning Prak, E.T. and K.E. Sullivan: Rituximab-treated patients have a poor response to influenza vaccination. J. Clin. Immunol. 33(2): 388-396, October 2012.

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Last updated: 04/02/2014
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