Eline Tjetske Luning Prak

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Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Assistant Director, Clinical Immunology Laboratory, Hospital of the University of Pennsylvania (HUP)
Facility Director, Human Immunology Core, Perelman School of Medicine, University of Pennsylvania
Co-Director, Immunology Core, Center for AIDS Research, Perelman School of Medicine, University of Pennsylvania
Department: Pathology and Laboratory Medicine

Contact information
405B Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-5768
Fax: (215 ) 573-6317
Lab: (215) 746-5769
Graduate Group Affiliations
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 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.

Rotation Projects
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
Dora Chen
Aaron Rosenfeld
Michelle Xu
Patricia Tsao, MD, PhD
Ling Zhao, MD, PhD
Yang Zhu Du, MD, PhD
Ping Wei, MD
Zheng Cui, PhD
Zhenyu Huang, MD, PhD
Yinan Lu
Hongen Wang

Description of Other Expertise

Research 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

Description of Itmat Expertise

Dr. Luning Prak studies the antibody repertoire in health and disease.

Selected Publications

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.

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.

Beer, L.A., Kossenkov, A.V., Liu, Q., Luning Prak, E.T., Domchek, S., Speicher, D.W. and B. Ky: Baseline Immunoglobulin E levels as a marker of doxorubicin- and trastuzumab-associated cardiac dysfunction. Circ Res 119(10): 1135-1144, October 2016.

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, Feb 2016 Notes: doi: 10.1016/j.clim.2015.12.004. Epub 2015 Dec 10.

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 Notes: doi: 10.1016/j.jim.2015.10.009. Epub 2015 Nov 1.

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Last updated: 05/27/2019
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