Helen Su, M.D., Ph.D.
Study findings explain why DOCK8-deficient patients are susceptible to infections.
Chief, Human Immunological Diseases Unit, LHD
The goals of the Human Immunological Diseases Unit (HIDU) are to understand the molecular mechanisms regulating the human immune system and how their derangements cause disease, with the objective of improving diagnosis and treatment. We study patients with a spectrum of poorly characterized, inherited immunodeficiencies and autoimmune diseases, who lack molecular diagnoses. These patients display combinations of 1) lymphocyte accumulation leading to enlarged spleens, lymph nodes, or lymphocyte infiltration into other organs such as the lungs; 2) immunodeficiencies that reflect defective lymphocyte function, with increased susceptibility to viral, fungal, or bacterial infections; and 3) autoimmunity, including hemolytic anemia and idiopathic thrombocytopenic purpura.
Besides patients with these features who cannot be easily classified, we are also studying patients who carry clinical diagnoses of DOCK8 deficiency (autosomal recessive hyper-IgE syndrome), caspase-8 deficiency state (CEDS) or autoimmune lymphoproliferative syndrome (ALPS) variants, X-linked immunodeficiency with Magnesium defect and Epstein-Barr Virus infection and Neoplasia (XMEN) disease, combined immunodeficiency (CID), common variable immunodeficiency (CVID), Evans syndrome, and familial hemophagocytic lymphohistiocytosis (FHLH). We have established close collaborations with several groups at the National Institutes of Health (NIH) to study these rare diseases, including the Laboratory of Immunology and the Laboratory of Clinical Infectious Diseases within NIAID and others outside NIH.
By combining clinical evaluations, assessments of lymphocyte function, biochemical and genetic analyses, and new technologies, we aim to define new clinical entities and discover novel or unappreciated roles of genes that regulate the human immune system. An example of this approach is illustrated by DOCK8 deficiency disease, in which comparative hybridization arrays revealed autosomal recessive mutations in the DOCK8 gene. This combined immunodeficiency disease features increased susceptibility to various infections, but especially viral skin infections, including herpes simplex virus, human papillomavirus, and molluscum contagiosum virus, severe allergic disease, and increased risk of developing skin cancers or lymphomas. Ongoing work in the laboratory is focused on understanding how DOCK8 deficiency impairs immune cell functions to cause this disorder. By applying similar experimental approaches to other unique patients, we hope to gain insights into the molecular regulation of the human immune system in both normal and diseased states.
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Helen Su received M.D. and Ph.D. degrees from Brown University. She completed training in pediatrics at St. Louis Children’s Hospital, Washington University, and subspecialty training in allergy and immunology at NIAID. After postdoctoral training with Michael Lenardo, M.D., in the Laboratory of Immunology, she joined the Laboratory of Host Defenses in 2007 as a tenure-track clinical investigator.
Huie JingQian ZhangYu Zhang Iam LambornMichael Leney-GreeneHeardley MurdockCorinne HappelAngela Wang
Jing H, Zhang Q, Zhang Y, Hill BJ, Dove CG, Gelfand EW, Atkinson TP, Uzel G, Matthews HF, Mustillo PJ, Lewis DB, Kavadas FD, Hanson IC, Kumar AR, Geha RS, Douek DC, Holland SM, Freeman AF, Su HC. Somatic reversion in dedicator of cytokinesis 8 immunodeficiency modulates disease phenotype. J Allergy Clin Immunol. 2014 Jun;133(6):1667-75.
Zhang Y, Yu X, Ichikawa M, Lyons JJ, Datta S, Lamborn IT, Jing H, Kim ES, Biancalana M, Wolfe LA, DiMaggio T, Matthews HF, Kranick SM, Stone KD, Holland SM, Reich DS, Hughes JD, Mehmet H, McElwee J, Freeman AF, Freeze HH, Su HC, Milner JD. Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment. J Allergy Clin Immunol. 2014 May;133(5):1400-9.
Chaigne-Delalande B, Li FY, O'Connor GM, Lukacs MJ, Jiang P, Zheng L, Shatzer A, Biancalana M, Pittaluga S, Matthews HF, Jancel TJ, Bleesing JJ, Marsh RA, Kuijpers TW, Nichols KE, Lucas CL, Nagpal S, Mehmet H, Su HC, Cohen JI, Uzel G, Lenardo MJ. Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science. 2013 Jul 12;341(6142):186-91.
Zhang Y, Su HC. Designs for massively parallel sequencing approaches to identify causal mutations in human immune disorders. Methods Mol Biol. 2013;979:175-87.
Snow AL, Xiao W, Stinson JR, Lu W, Chaigne-Delalande B, Zheng L, Pittaluga S, Matthews HF, Schmitz R, Jhavar S, Kuchen S, Kardava L, Wang W, Lamborn IT, Jing H, Raffeld M, Moir S, Fleisher TA, Staudt LM, Su HC, Lenardo MJ. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J Exp Med. 2012 Nov 19;209(12):2247-61.
Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC, Cohen JI, Uzel G, Su HC, Lenardo MJ. Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature. 2011 Jul 27;475(7357):471-6.
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Information for Patients and Referring PhysiciansA patient may be considered for our research studies through referral by his or her personal physician. To determine eligibility, we generally request a referral letter that contains a concise summary of the patient’s medical history and relevant laboratory tests. The NIH Clinical Center's Patient Recruitment Office can provide general information about clinical research protocols across all NIH institutes.
The HIDU participates in the following clinical protocols, which are actively recruiting patients:
Last Updated June 26, 2014
Last Reviewed June 26, 2014