Eline Tjetske Luning Prak, MD, PhD
422 Curie Blvd.
Philadelphia, PA 19104
Fax: (215 ) 573-6317
Lab: (215) 746-5769
A.B. (Molecular Biology)
Princeton University , 1988.
University of Pennsylvania, 1996.
University of Pennsylvania, 1996.
Description of Research ExpertiseResearch Interests
Dr. Luning Prak studies the antibody repertoire in health and disease.
Key words: antibody, antibody repertoire, V(D)J recombination, receptor editing, immunoglobulin, autoimmunity, clone tracking, minimal residual disease
Description of Research
Antibodies are proteins produced by B lymphocytes that are important for immune defense, but also serve as ubiquitous biomarkers for immunity and disease. The proliferation of B cells derived from a single precursor cell (i.e., a clone) can reflect a robust immune response, an autoimmune disease process or herald B cell malignancy. Each B cell usually makes only one kind of antibody and each person has about 100 billion different B cells (this collection is called the antibody "repertoire"). My lab studies the B cell repertoire by sequencing the DNA rearrangements that create antibodies. These DNA rearrangements are diverse; hence, when sufficiently similar rearrangements are observed, they are likely to derive from B cells that are clonally related. By studying the clonal landscape of the human B cell repertoire using next-generation sequencing (NGS), we hope to better understand how B cells mature and evolve in different organs in health and disease. We are also harnessing this knowledge to create clinical lab tests that identify and track B cell clones.
1. An anatomic atlas of large B cell clones in the human body. By sequencing antibody heavy chain variable regions in different tissues of organ donors, we can trace how large B cell clones are distributed in the body. So far, we have found two major networks of clones, one in the blood/bone marrow/spleen/lung and another in the gastrointestinal tract. We also observed that the B cells in the GI tract, and especially the jejunum, have more somatic hypermutations. One of the most interesting aspects of this work was the finding that some individuals, but not others, had very large standing B cell clones. We are focusing on defining the antigens drive the formation of these clones by capturing their antibodies and characterizing their antigenic specificity.
2. Ontogeny of human B cell subsets. How human B cell subsets, particularly memory B cells (MBCs), develop and evolve remains poorly understood. We have been studying human B cell subset maturation in the blood and have published several papers describing how B cell subsets shift with time, with age, and during autoreconstitution following chemotherapy or immunosuppression. In this ongoing project, we have been tracking individual clones through different B cell subsets sorted from blood, bone marrow and other human tissues. These studies reveal a surprising degree of clonal sharing between subsets, suggesting that differentiation is not unidirectional or that certain subsets have cells with self-renewal and/or maintenance capacities, or that our definitions of the subsets are flawed.
3. Clone tracking and B cell subset analysis in autiommunity. Our longstanding hypothesis, based upon our work and the work of others, is that patients with certain forms of autoimmunity harbor pathogenic expanded B cell clones. We hope to define pathogenic B cell clones that expand during disease flares and potentially gain insights into their subset of origin and manner of tolerance breakdown, building upon our ongoing work in autoimmunity. In this ongoing project, we are tracking clonal lineages in blood and in some cases tissues from individuals with different autoimmune diseases including systemic lupus erythematosus and type 1 diabetes.
4. Clone tracking in malignancy. We are interested in developing and validating robust next generation sequencing (NGS) based methods to identify and track malignant and non-malignant B cell clones and lymphocyte subsets in patients with hematologic malignancies including multiple myeloma, chronic lymphocytic leukemia, acute lymphoblastic leukemia and other malignant and pre-malignant conditions. In addition to developing minimal residual disease NGS assays, we are studying the non-malignant B and T cell repertoires in cancer patients. Features of the non-malignant immune repertoire, such as its diversity and degree of somatic hypermutation, may inform immune therapies and provide prognostic information.
Lab and core lab personnel:
Wenzhao Meng, PhD
Patricia Tsao, MD, PhD
Ling Zhao, MD, PhD
Yang Zhu Du, MD, PhD
Ping Wei, MD
Zheng Cui, PhD
Zhenyu Huang, MD, PhD
Description of Clinical ExpertiseMolecular Immunology- I have expertise in next-generation sequencing based assays of immune repertoires and computational analysis of the immune repertoire. Iimmune repertoire profiling can be used clinically for the evaluation of immunodeficiency, for diagnosis of B or T cell malignancy or lymphoproliferative disorder and for minimal residual disease evaluation. I co-chair a working group that is establishing data standards for NGS immune repertoire profiling studies (part of the international Adaptive Immune Receptor Repertoire (AIRR) Community).
Flow Cytometry- I have expertise in clinical and translational immunophenotyping experiments. I direct a core lab (Human Immunology Core) that develops and performs multicolor immunophenotyping panels for early-phase clinical trials. I am especially familiar with human B cell lymphocyte maturation, but also provide input into the design of immunophenotyping panels for malignant B and T cell disorders. I also serve as a consultant to HUP allergy immunology physicians who use clinical flow cytometry data as part of an immunodeficiency evaluation.
Autoimmune and infectious disease serology- I have expertise in autoimmune serology, autoantibody profiling and serologic assays for infectious diseases including lyme disease. I help direct the Clinical Immunology laboratory at the Hospital of the University of Pennsylvania, which performs a wide range of assays.
HLA typing and allosensitization evaluations- I have expertise in HLA and anti-HLA immune responses, and provide input into clinical test design, evaluation and test reporting for the HLA lab at the Hospital of the University of Pennsylvania.
Description of Other ExpertiseResearch advisor to students at all levels
Mentoring of MSTP students, senior residents, fellows and junior faculty
Scientific consultation-- providing researchers and clinicians with assistance in experimental design, appropriate immunology tests to support their research or clinical objectives
Selected PublicationsRitz, C., Meng, W., Stanley, N., Baroja, M., Xu, C., Yan, P., Huang, A., Hausler, R., Nicholas, P., Fan, J.M., Lieberman, D., Carreno, B., Luning Prak, E.T., Olson, T. and D. Babushok: Post-vaccination graft dysfunction/aplastic anemia relapse with massive clonal expansion of autologous CD8+ lymphocytes. Blood Advances in press 2020.
Horvath, S., Tsao, P.Y., Huang, Z-Y, Zhao, L., Du, Y., Sammel, M.D., Luning Prak, E.T. and Schreiber, C.A.: The concentration of fetal red blood cells in first-trimester pregnant women undergoing uterine aspiration is below the calculated threshold for Rh sensitization. Contraception in press 2020.
Pillai, V., Muralidharan, K., Meng, W., Bagashev, A., Oldridge, D., Rosenthal, J., Van Arnam, J., Melenhorst, J., Mohan, D., DiNofia, A., Luo, M., Cherian, S., Fromm, J., Wertheim, G., Thomas-Tikhonenko, A., Paessler, M., June, C., Luning Prak, E.T., Bhoj, V., Grupp, S., Maude, S. and S. Rheingold: CAR T cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy. Blood Advances in press 2019.
Belman, JP, Meng, W, Wang, HY, Li, J., Strauser, HT, Rosenfeld, AM, Zhang, Q, Luning Prak, ET and MA Wasik: Dramatic increase in gene mutational burden after transformation of follicular lymphoma into TdT+ B-cell lymphoblastic lymphoma/leukemia. Cold Spring Harbor Molecular Case Studies in press 2019.
Miron, M., Kumar, B.V., Meng, W., Granot, T., Carpenter, D.J., Senda, T., Chen, D., Rosenfeld, A., Zhang, B., Lerner, H., Friedman, A.L., Hershberg, U., Shen, Y., Rahman, A., Luning Prak, E.T. and D.L. Farber.: Human lymph nodes maintain quiescent memory T cells with high functional potential and clonal diversity throughout life. J. Immunol. 201(7): 2132-2140, October 2018.
Rosenfeld, A.M., Meng, W., Luning Prak, E.T. and U. Hershberg: ImmuneDB, a novel tool for the analysis, storage, and dissemination of immune repertoire sequencing data. Frontiers in Immunology 9: 2107, Sep 2018 Notes: doi: 10.3389/fimmu.2018.02107. eCollection 2018.
Rosenfeld, A.M., Chen, D.Y., Meng, W., Zhang, B., Granot, T., Farber, D.L., Hershberg, U. and E.T. Luning Prak: Computational evaluation of B-cell clone sizes in bulk populations. Frontiers in Immunology. Greg Ippolito (eds.). 9: 1472, June 2018 Notes: Published online 2018 Jun 29. doi: 10.3389/fimmu.2018.01472.
Javaheri, A., Wang, A.R., Luning Prak, E.T., Lal, P., Goldberg, L.R. and M. Kamoun: Fatal Accelerated Rejection with a Prominent Natural Killer Cell Infiltrate in a Heart Transplant Patient with Peripartum Cardiomyopathy. Transplant Immunology 47: 49-54, April 2018 Notes: doi: 10.1016/j.trim.2017.10.002. Epub 2017 Oct 31.
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. Elsevier, 183: 336-343, Oct 2017 Notes: doi: 10.1016/j.clim.2017.09.021. Epub 2017 Sep 23.
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.