Helen Su, M.D., Ph.D.
Chief, Human Immunological Diseases Unit
Tenure-Track Clinical Investigator
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 Mike Lenardo, M.D., in the Laboratory of Immunology (LI), she joined the Laboratory of Host Defenses in 2007 as a tenure-track clinical investigator.
Description of Research Program
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 caspase-8 deficiency state (CEDS) or autoimmune lymphoproliferative syndrome (ALPS) variants, common variable immunodeficiency (CVID), Evans syndrome, and familial hemophagocytic lymphohistiocytosis (FHLH). We have established close collaborations with several groups at NIH to study these rare diseases, including the LI and the Laboratory of Clinical Infectious Diseases within NIAID and others outside of the 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 caspase-8 deficiency, an autosomal recessive disorder that causes a prominent combined immunodeficiency because of poor activation of lymphocytes, as well as mild lymphoaccumulation and autoimmunity. By studying these patients, we discovered that caspase-8 is important not only for apoptosis induction but also for activation of the gene transcription factor nuclear factor κB (NF-κB), which is necessary for normal lymphocyte function. Mechanistically, caspase-8 is able to control two seemingly disparate fundamental cellular processes by participating in distinctly different signaling complexes depending on its molecular form.
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| Caspase-8 participates in two signaling complexes: the death inducing signaling complex (DISC) and the activation receptor induced signalosome (ARIS). In the former, death receptor stimulation results in caspase-8 activation and cleavage of downstream caspases, leading to the cell’s death. In the latter, immunoreceptor stimulation leads to caspase-8-dependent recruitment of the CARMA1 (Card11), Bcl10, MALT1 (CBM)-IκB kinase (IKK) complex and NF-κB activation. Caspase-8 deficiency state (CEDS) due to loss-of-function caspase-8 mutations causes an inherited disease with features of lymphoaccumulation, autoimmunity, and combined immunodeficiency. View a larger version. |
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.
Research Group Members
Ian Lamborn, Huie Jing, Qian Zhang
Clinical Research Protocols
The HIDU participates in the following clinical protocols, which are actively recruiting patients:
Information for Patients and Referring Physicians
A 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.
Selected Publications
Su H, Bidere N., Zheng L, Cubre A, Sakai K, Dale J, Salmena L, Hakem R, Straus S, Lenardo M. Requirement for caspase-8 in NF-kB activation by antigen receptor. Science 2005;307:1465-8.
Lemmers B, Salmena L, Bidere N, Su H, Matysiak-Zablocki E, Murakami K, Ohashi PS, Jurisicova A, Lenardo M, Hakem R, Hakem A. Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling. J Biol Chem. 2007;282:7416-23.
Su HC, Lenardo MJ. Genetic defects of apoptosis and primary immunodeficiency. Immunol Allergy Clin North Am. 2008;28:329-51.
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