Specialty Division

Laboratory Medicine, Cancer and Immunobiology

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

Clinical Expertise

Molecular 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.

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

Itmat Expertise

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

Graduate Groups

Cell and Molecular Biology
Immunology

Education

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

Specialty Certification

Diplomate, National Board of Medical Examiners, 1999
Diplomate Clinical Pathology Boards, 1999
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
Saul Winegrad Thesis Prize, Biomedical Graduate Studies, University of Pennsylvania, 1996
Stuart Mudd Award for Excellence in Microbiology/Immunology Research, PSOM, 1996
Leonard Berwick Resident Teaching Award, PSOM, 1998
William Pepper Fellow in Clinical Pathology, Hospital of the University of Pennsylvania, 1998-1999
Outstanding Discussion Group Leader (awarded by Penn Medical Students for Immunology section), PSOM, 2001
The Peter C. Nowell Award for Excellence in Teaching, PSOM, 2004
Leonard Berwick Memorial Teaching Award, PSOM, 2005
Morton Klein Distinguished Speaker
Temple University School of Medicine, 2009
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 Association of Immunologists, 2004 - Present
American Society of Clinical Pathology, 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
Congressionally Directed Medical Research Program, 2013 - 2013
Arthritis Foundation, 2013 - 2013
German-Israel Foundation for Science, 2013 - 2013
The Dunhill Medical Trust, 2014 - Present
Adaptive Immune Receptor Repertoire Community (AIRR-C), 2015 - present
National Institutes of Health, 2016 - 2017
Juvenile Diabetes Research Foundation, 2018 - Present
The Antibody Society, 2019 - Present
Roche Diagnostics, 2020 - 2020
Immune Epitope Database (IEDB), 2020 - Present
American Autoimmune Related Diseases Association, Inc., 2020 - 2022
Institute for Diabetes, Obesity and Metabolism, 2021 - Present
UKRI Medical Research Council, 2021 - Present
Israeli Ministry for Innovation, Science and Technology, 2022 - Present
Autoimmunity Association, 2022 - Present
Israel Science Foundation, 2022 - Present
Chan Zuckerberg Institute, 2022 - Present

Web Links

Selected Publications

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