Julie E. Niemela
A5062959666- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Magnesium in Health and Disease
- Viral-associated cancers and disorders
- NF-κB Signaling Pathways
- Lymphoma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Blood disorders and treatments
- Galectins and Cancer Biology
- Acute Lymphoblastic Leukemia research
- Inflammasome and immune disorders
- RNA modifications and cancer
- Mycobacterium research and diagnosis
- Eosinophilic Disorders and Syndromes
- Peptidase Inhibition and Analysis
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Analytical Chemistry and Sensors
- IL-33, ST2, and ILC Pathways
- Neurogenetic and Muscular Disorders Research
- Acute Myeloid Leukemia Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Fungal Infections and Studies
National Institutes of Health Clinical Center
2016-2025
National Institute of Allergy and Infectious Diseases
2009-2022
National Institutes of Health
2002-2021
National Institute of Genomic Medicine
2021
National Institute of Health
2021
Children's Hospital of Pittsburgh
2020
Hospital Virgen de la Salud
2020
Universidade de São Paulo
2020
Center for Clinical Research (United States)
2007-2015
Cardinal Glennon Children’s Medical Center
2010-2012
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 humans are unknown. We identified germline heterozygous subjects with severe dysregulation from four unrelated families. Whereas Ctla4 mice have no obvious phenotype, human haploinsufficiency caused FoxP3(+) regulatory (Treg) cells, hyperactivation effector and lymphocytic infiltration target organs. Patients also exhibited progressive loss circulating B...
Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families four different ethnic groups. These were homozygous for one null mutations, that seen P1. They displayed mycobacterial and/or infections, but no HIES. All eight impaired...
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous
Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause unknown majority cases, and less than 10% patients have a family history disease. Most normal numbers B cells but lack plasma cells.
STAT6 (signal transducer and activator of transcription 6) is a factor that plays central role in the pathophysiology allergic inflammation. We have identified 16 patients from 10 families spanning three continents with profound phenotype early-life onset immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, anaphylaxis. The cases were either sporadic (seven...
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to large group of RAG-mutated patients, we aimed at characterizing the immunopathology associated each phenotype. Although defective T B cell development is common all phenotypes, patients hypomorphic RAG variants generate cells signatures immune dysregulation produce autoantibodies broad range self-antigens, including type I interferons....
The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization, other signaling networks, is the most frequent target activating mutations in cancer. Activating germline KRAS HRAS cause severe developmental abnormalities leading to Noonan, cardio-facial-cutaneous, Costello syndrome, but NRAS have not been reported. Autoimmune lymphoproliferative syndrome (ALPS) common genetic disease lymphocyte apoptosis causes autoimmunity as...
Ikaros/IKZF1 is an essential transcription factor expressed throughout hematopoiesis. IKZF1 implicated in lymphocyte and myeloid differentiation negative regulation of cell proliferation. In humans, somatic mutations have been linked to the development B acute lymphoblastic leukemia (ALL) children adults. Recently, heterozygous germline identified patients with a immune deficiency mimicking common variable immunodeficiency. These demonstrated incomplete penetrance led haploinsufficiency....
Interferon regulatory factor 4 (IRF4) is a transcription (TF) and key regulator of immune cell development function. We report recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) seven patients from six unrelated families. The exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii , presented with agammaglobulinemia. Patients’ B cells showed impaired maturation, decreased immunoglobulin isotype...
Primary immunodeficiencies (PIDs) are a diverse group of disorders caused by multiple genetic defects. Obtaining molecular diagnosis for PID patients using phenotype-based approach is often complex, expensive, and not always successful. Next-generation sequencing (NGS) methods offer an unbiased genotype-based approach, which can facilitate diagnostics.To develop efficient NGS method to identify variants in PID-related genes.We performed HaloPlex custom target enrichment the Ion Torrent PGM...
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by
Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM performed whole-exome sequencing. In an exploratory set 67 DCM, 2 had haploinsufficient STAT3 mutations, defects β-glucan sensing response were seen 34 cases. Damaging CLEC7A...