Luigi D. Notarangelo

Luigi D. Notarangelo, M.D., is Chief of the Immune Deficiency Genetics Section and Deputy Chief of the Laboratory of Clinical Immunology and Microbiology (LCIM) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). He is also an NIH Distinguished Investigator, reflecting his significant contributions to biomedical research. Dr. Notarangelo provides clinical care at the NIH Clinical Center and leads a research program focused on the genetic basis of primary immune deficiencies.

• University: National Institutes of Health
• School: Division of Intramural Research
• Department: Laboratory of Clinical Immunology and Microbiology
• Academic Rank: NIH Distinguished Investigator

Dr. Notarangelo's research centers on inborn errors of immunity, particularly combined immunodeficiencies (CID). His laboratory employs genomic and cellular approaches—including whole exome sequencing, induced pluripotent stem cells (iPSCs), artificial thymic organoids, and single-cell RNA sequencing—to identify novel gene defects and understand disease mechanisms. His team has discovered several new genetic causes of immunodeficiency, such as DOCK2, TTC7A, HOIP, EXTL3, PAX1, and SASH3. A major focus is on understanding immune dysregulation in patients with RAG deficiency and other V(D)J recombination defects, using in vitro models to study T- and B-cell repertoire diversity and thymic stromal interactions.

His recent publications reflect a strong trend in understanding immune responses in pediatric infectious diseases, particularly in the context of SARS-CoV-2 and MIS-C. Studies on autoantibodies against type I interferons have provided critical insights into the genetic and immunological basis of severe viral infections. The use of artificial thymic organoids and CRISPR-based gene correction strategies highlights a translational focus on developing future therapies for immune deficiencies.

• Election to the National Academy of Medicine (2019)
• President of the European Society for Immunodeficiencies
• President of the Clinical Immunology Society

Dr. Notarangelo has mentored numerous researchers and clinicians, many of whom are listed as members of his research group. His lab has been supported by intramural funding from NIAID and has contributed to major clinical initiatives, including newborn screening for SCID and the development of diagnostic criteria for primary immunodeficiencies. His research integrates basic science with clinical application, aiming to improve diagnosis and treatment for patients with rare immune disorders.

His laboratory maintains a large repository of patient-derived iPSCs and uses advanced models to study thymic development and immune cell differentiation. Ongoing work includes exploring the role of the microbiome in immune dysregulation and testing gene correction strategies for therapeutic use.