About

Jordan S. Orange, MD, PhD, is a Professor of Pediatrics (Allergy/Immunology) at the University of Pennsylvania's Perelman School of Medicine. His research focuses on natural killer (NK) cells, which are lymphocytes critical to host defense, playing important roles in tumor surveillance and viral infection control. His laboratory investigates the formation, function, and regulation of the NK cell immunologic synapse (NKIS), emphasizing the role of the cytoskeleton, particularly actin and microtubules, in these processes. He has studied how actin-dependent mechanisms facilitate NK cell cytotoxicity and how molecular rearrangements at the NKIS influence activation-induced transcriptional regulation and cytotoxic function. His work includes examining the sequential steps required for NKIS formation, the role of actin complex-associated proteins in granule localization, and the impact of cytoskeletal dynamics on NK cell activity. Dr. Orange's research also explores the molecular mechanisms underlying NK cell deficiencies, such as Wiskott-Aldrich syndrome, and their implications for immune function.

Research topics

• Genetics
• Biology
• Immunology
• Medicine
• Internal medicine
• Pediatrics
• Cancer research
• Cell biology
• Dermatology
• Environmental health

Selected publications

• What We Have Here Is a Failure to Communicate: Interleukin-12 / Interferon-gamma Axis Defects and Mendelian Susceptibility to Mycobacterial Disease

  The Journal of Allergy and Clinical Immunology In Practice · 2026-03-01

  articleOpen access
  PublisherOA PDFDOI

• 2025 Inborn errors of immunity practice parameter

  Annals of Allergy Asthma & Immunology · 2026-04-01 · 2 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Immunoglobulin replacement therapy in primary immunodeficiency disorders: Pragmatic review and evidence mapping

  Journal of Allergy and Clinical Immunology Global · 2026-03-19

  articleOpen accessSenior author

  Background: Immunoglobulin replacement therapy (IgRT) is used in the treatment of patients with primary immunodeficiency disorders (PIDDs). There are some references to differences between preparations in terms of characteristics and efficacy, though comparative evidence is limited. Objectives: We sought to identify and map the evidence-base of clinical outcomes and adverse events of IgRT studies used for the treatment of patients with PIDDs and determine any signals of difference in treatment effect between different immunoglobulin brands. Methods: A pragmatic literature search was conducted in February 2023 to identify studies assessing the efficacy of IgRT in PIDDs, and an assessment of the feasibility of indirect treatment comparisons (ITC) was carried out. Annualized outcome data were presented in visualization plots and possible outlier results identified through naive (unanchored, unadjusted) comparisons; results were considered outliers when no overlap in confidence interval was identified. Results: After single-reviewer screening, 103 studies were included; 70 prospective studies were prioritized for extraction. A feasibility assessment found that ITC was not possible. Few outlier results for any particular commercial IgRT brand were identified across the outcomes considered, and those that were identified may have been due to differences in study methods or intervention characteristics rather than differing efficacy. Conclusions: Limited evidence on the comparative efficacy of different IgRT brands was identified. Reporting in studies of IgRT for PIDDs was found to vary widely, such that ITC was not possible. We recommend improving reporting to enable such comparisons in the future, including suggestions on improving or standardizing reporting of patient and study characteristics, outcome definitions, and follow-up duration and measures of variance.

  PublisherDOI

• The Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity

  Cell Reports · 2025-01-01 · 3 citations

  articleOpen accessSenior author

  Cytotoxic immune cells mediate precise attacks against diseased cells to maintain organismal health. Their operational unit of killing and host defense is lytic granules (LGs), which are specialized lysosomal-related organelles. Precision in cytotoxicity is achieved by converging the many LGs to the microtubule-organizing center (MTOC) and polarizing these to the diseased cell for secretion. We identify unappreciated intimate relationships between the Golgi, MTOC, and LGs after cytotoxic cell activation, as well as the trans-Golgin protein GCC2 on the LG surface. GCC2 serves to tether LGs to the Golgi following convergence, and both GCC2 and the Golgi are required for the persistence of convergence. GCC2 allows LGs to utilize the Golgi as a docking station preventing LG dispersion and innocent bystander killing in complex three-dimensional environments. We also identify GCC2 variants causing human natural killer cell deficiency, further emphasizing the importance of LG convergence and Golgi linkage in precision targeting for human immunity.

  PublisherDOI

• Reported Demographics of Primary Immunodeficiency Diseases in the United States

  The Journal of Allergy and Clinical Immunology In Practice · 2025-09-01

  articleSenior author
  PublisherDOI

• Proceedings of the second Artificial Intelligence in Primary Immunodeficiency (AIPI) meeting

  Journal of Allergy and Clinical Immunology · 2025-09-17 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Monoallelic expression can govern penetrance of inborn errors of immunity

  Nature · 2025-01-01 · 69 citations

  articleOpen access
  PublisherOA PDFDOI

• The crucial impact of NIH funding on allergy/immunology patient care and research

  Journal of Allergy and Clinical Immunology · 2025-06-23

  editorialOpen access

  Through the innovative work of investigators supported by National Institutes of Health (NIH) funding, the United States is acknowledged as the global leader in biomedical research. This dominance has stretched over 80 years1 and has resulted in an unprecedented number of new therapies that have revolutionized medical practice. The NIH investment in the field of allergy and immunology has produced new biologic therapies and drugs that affect virtually all disorders cared for by allergists and immunologists, providing relief for patients experiencing the very common forms of allergic disease, including asthma, food allergy, and atopic dermatitis.

  PublisherOA PDFDOI

• Introduction on Inborn Errors of Immunity

  2025-01-01 · 1 citations

  book-chapter
  PublisherDOI

• Mitigating Privacy and Security Risks of Federated Learning in Smart Healthcare

  2025-11-21

  book-chapterSenior author
  PublisherDOI

Recent grants

• Directing Function at the Natural Killer Cell Secretory Immunological Synapse

  NIH · $4.0M · 2005–2020

• NIH Grant R56AI067946

  NIH · $335k · 2012

• Genetic, Immunologic and Mechanistic Basis of Human NK Cell Deficiency

  NIH · $815k · 2016–2020

• Directing Function at the Natural Killer Cell Secretory Immunological Synapse

  NIH · $393k · 2005–2020

• Genetic, Immunologic and Mechanistic Basis of Human NK Cell Deficiency

  NIH · $6.9M · 2016–2026

Frequent coauthors

• Javier Chinen

  Baylor College of Medicine

  461 shared

• William Lane M. Robson

  450 shared

• Alexander K. C. Leung

  340 shared

• Alexander K. C. Leung

  299 shared

• Donatus Nöhr

  University of Hohenheim

  286 shared

• Emily M. Mace

  Columbia University

  277 shared

• Dieter Kaufmann

  Clausthal University of Technology

  220 shared

• Iván K. Chinn

  Texas Children's Hospital

  175 shared

Labs

• Jordan S. Orange LabPI

Awards & honors

• Featured in Biophotonics