Hye Sun Kuehn, PhD

PhD, Ewha Womans University
MS, Ewha Womans University
BS, Ewha Womans University

Dr. Kuehn received her MS and PhD from the Department of Molecular Life Science of EWHA Woman’s University in Seoul, Korea. In 2010, she joined the Department of Laboratory Medicine (DLM) at the NIH Clinical Center as a research biologist in the Immunology Service and has served as a Staff Scientist since 2014. In 2021, she was awarded the honorary title of NIH Senior Associate Scientist, and in 2024, she was designated as the Deputy Chief of the Immunology Service, DLM.

The Immunology Service Research is focused on the molecular and immunological study of genetic causes of Primary Immunodeficiency disorder (PID)/ inborn errors of immunity (IEI). PID and IEI refers to a heterogenous group of disorders with a wide spectrum of clinical manifestations including recurrent infections, autoimmune diseases and malignancies. Her research focuses on identifying both monogenic and complex genetic forms of PID using next-generation sequencing and advanced technologies, developing functional and molecular immunology tests to validate genetic pathogenic variants, and defining the molecular and cellular mechanisms of candidate gene and allelic variants in PID. Her recent work has focused on IKAROS family-associated diseases (IKAROS, AIOLOS, HELIOS), and transcription factors such as Nuclear Factor Kappa B (NF-κB), IRF4, and TCF3 in PID/IEI.

• NIH Clinical Center CEO Awards, 2021
• NIH Clinical Center CEO Awards, 2020
• Clinical Center Director’s Awards, 2016
• NIAID Merit Awards, 2015

Kuehn HS, Bosticardo M, Arrieta AC, Stoddard JL, Pala F, Niemela JE, Gil Silva AA, King PL, Esteve-Sole A, Naveen A, Anaya E, Truong PM, Delmonte OM, Buchbinder DK, Rosenzweig SD, Notarangelo LD. Thymic and T-cell intrinsic critical roles associated with severe combined immunodeficiency and Omenn syndrome due to a heterozygous variant (G201R) in PSMB10. Allergy Clin Immunol 10.1016/j.jaci.2024.12.1082 (2024).

Kuehn HS, Sakovich IS, Niemela JE, Gil Silva AA, Stoddard JL, Polyakova EA, Esteve Sole A, Aleshkevich SN, Uglova TA, Belevtsev MV, Vertelko VR, Shman TV, Kupchinskaya AN, Walter JE, Fleisher TA, Notarangelo LD, Peng XP, Delmonte OM, Sharapova SO, Rosenzweig SD. Disease-associated AIOLOS variants lead to immune deficiency/dysregulation by haploinsufficiency and redefine AIOLOS functional domains. J Clin Invest 134 (2024).

Consortium IRFI, Fornes O, Jia A, Kuehn HS, Min Q, et al. A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency. Sci Immunol 8, eade7953 (2023).

Kuehn HS, Chang J, Yamashita M, Niemela JE, Zou C, Okuyama K, Harada J, Stoddard JL, Nunes-Santos CJ, Boast B, Baxter RM, Hsieh EWY, Garofalo M, Fleisher TA, Morio T, Taniuchi I, Dutmer CM, Rosenzweig SD. T and B cell abnormalities, pneumocystis pneumonia, and chronic lymphocytic leukemia associated with an AIOLOS defect in patients. J Exp Med 218 (2021).

Kuehn HS, Niemela JE, Stoddard J, Mannurita SC, Shahin T, Goel S, Hintermeyer M, Heredia RJ, Garofalo M, Lucas L, Singh S, Tondo A, Jacobs Z, Gahl WA, Latour S, Verbsky J, Routes J, Cunningham-Rundles C, Boztug K, Gambineri E, Fleisher TA, Chandrakasan S, Rosenzweig SD. Germline IKAROS dimerization haploinsufficiency causes hematologic cytopenias and malignancies. Blood 137, 349-363 (2021).

Boutboul D*, Kuehn HS*, Van de Wyngaert Z, Niemela JE, Callebaut I, Stoddard J, Lenoir C, Barlogis V, Farnarier C, Vely F, Yoshida N, Kojima S, Kanegane H, Hoshino A, Hauck F, Lhermitte L, Asnafi V, Roehrs P, Chen S, Verbsky JW, Calvo KR, Husami A, Zhang K, Roberts J, Amrol D, Sleaseman J, Hsu AP, Holland SM, Marsh R, Fischer A, Fleisher TA, Picard C, Latour S, Rosenzweig SD. Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency. Clin Invest 128, 3071-3087 (2018).

Kuehn HS, Niemela JE, Sreedhara K, Stoddard JL, Grossman J, Wysocki CA, de la Morena MT, Garofalo M, Inlora J, Snyder MP, Lewis DB, Stratakis CA, Fleisher TA, Rosenzweig SD. Novel nonsense gain-of-function NFKB2 mutations associated with a combined immunodeficiency phenotype. Blood 130, 1553-1564 (2017).

Kuehn HS, Boisson B, Cunningham-Rundles C, Reichenbach J, Stray-Pedersen A, Gelfand EW, Maffucci P, Pierce KR, Abbott JK, Voelkerding KV, South ST, Augustine NH, Bush JS, Dolen WK, Wray BB, Itan Y, Cobat A, Sorte HS, Ganesan S, Prader S, Martins TB, Lawrence MG, Orange JS, Calvo KR, Niemela JE, Casanova JL, Fleisher TA, Hill HR, Kumanovics A, Conley ME, Rosenzweig SD. Loss of B Cells in Patients with Heterozygous Mutations in IKAROS. N Engl J Med 374: 1032-43 (2016)

Kuehn HS*, Ouyang W*, Lo B*, Deenick EK, Niemela JE, Avery DT, Schickel JN, Tran DQ, Stoddard J, Zhang Y, Frucht DM, Dumitriu B, Scheinberg P, Folio LR, Frein CA, Price S, Koh C, Heller T, Seroogy CM, Huttenlocher A, Rao VK, Su HC, Kleiner D, Notarangelo LD, Rampertaap Y, Olivier KN, McElwee J, Hughes J, Pittaluga S, Oliveira JB, Meffre E, Fleisher TA, Holland SM, Lenardo MJ, Tangye SG, Uzel G. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 345: 1623-7 (2014)

Lucas CL*, Kuehn HS*, Zhao F*, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol 15: 88-97 (2014)