Eline Tjetske Luning Prak, MD, PhD
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
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-5768
Fax: (215 ) 573-6317
Fax: (215 ) 573-6317
Email:
luning@mail.med.upenn.edu
luning@mail.med.upenn.edu
Publications
Links
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Immunology graduate group faculty webpage.
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Immunology graduate group faculty webpage.
Education:
A.B. (Molecular Biology)
Princeton University , 1988.
Ph.D. (Immunology)
University of Pennsylvania, 1996.
M.D.
University of Pennsylvania, 1996.
Permanent linkA.B. (Molecular Biology)
Princeton University , 1988.
Ph.D. (Immunology)
University of Pennsylvania, 1996.
M.D.
University of Pennsylvania, 1996.
Description of Research Expertise
Research InterestsDr. 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 for 2009-2010
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
Selected Publications
Habib, T., Funk, A., Rieck, M., Brahmandam, A., Dai, X., Panigrahi, A., Luning Prak, E., Meyer-Bahlburg, A., Sanda, S., Greenbaum, C., Rawlings, D. and J. Buckner.: Altered B cell homeostasis is associated with Type I diabetes and carriers of the PTPN22 allelic variant. J. Immunol. 188(1): 487-496, January 2012.Meng, W., Li, Y., Xue, E., Satoh, M., Peck, A.B., Cohen, P.L., Eisenberg, R.A. and E. T. Luning Prak.: B-cell tolerance defects in the B6.Aec1/2 mouse model of Sjogren's syndrome. Journal of Clinical Immunology. Springer, in press 2012.
Sekiguchi, D.R., Smith, S.B., Sutter, J.A., Goodman, N.G., Propert,K.J., Louzoun, Y., Rogers, W. and E.T. Luning Prak: Circulating lymphocyte subsets in normal adults are variable and can be clustered into sub-groups. Cytometry Part B 80B: 291-299, September 2011.
Meng, W., Yunk, L., Wang, L-S, Maganty, A., Xue, E., Cohen, P.L., Eisenberg, R.A., Weigert, M.G., Mancini, S.J.C. and E.T. Luning Prak: Selection of individual VH genes occurs at the pro-B to pre-B cell transition. J. Immunol 187(4): 1835-1844, August 2011.
Jawad, A.F., Luning Prak, E., Boyer, J., McDonald-McGinn, D., Zackai, E., McDonald, K. and K. Sullivan.: A prospective study of influenza vaccination and a comparison of immunologic parameters in children and adults with chromosome 22qdel11.2 deletion syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome). J. Clin. Immunol. in press, August 2011.
Luning Prak, E.T., Ross, J., Sutter, J. and K. E. Sullivan : Age-Related Trends in Pediatric B cell Subsets. Pediatric and Developmental Pathology 14(1): 45-52, Jan-Feb 2011.
O. Kalinina, C. Doyle-Cooper, J. Miksanek, W. Meng, E. Luning Prak and M. Wiegert.: Alternative Mechanism of Receptor Editing in Autoreactive B cells. Proc. Natl. Acad. Sci. U.S.A. 108(17): 7125-7130, 2011.
Debora R. Sekiguchi, Jennifer A. Sutter, Michael R. Rickels, Ali Naji, Chengyang Liu, Kathleen J. Propert, Wade T. Rogers and Eline T. Luning Prak: Analysis of B cell subsets following pancreatic islet cell transplantation in a patient with type 1 diabetes by cytometric fingerprinting. J. Immunol. Methods 363(2): 233-244, 2011.
Braunstein, I., Goodman, N.G., Rosenbach, M., Okawa, J., Shah, A., Krathen, M., Kovarik, C., Luning Prak, E.T. and V.P. Werth: Lenalidomide therapy in treatment refractory cutaneous lupus erythematosus: Histologic and circulating leukocyte profile and potential risk of a systemic lupus flare. Journal of the American Academy of Dermatology in press 2011.
Rickels, M., Soleimanpour, S., Sekiguchi, D., LaRosa, D., Luning Prak, E. and A. Naji.: Hypersensitivity to rabbit anti-thymocyte globulin in an islet transplant recipient: a case report. Transplantation Proceedings. Elsevier, 43: 3302-3306, 2011.