A5088114256- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Neurological diseases and metabolism
- Prion Diseases and Protein Misfolding
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Sphingolipid Metabolism and Signaling
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- Cell Adhesion Molecules Research
- Retinal Diseases and Treatments
- Urticaria and Related Conditions
- Pluripotent Stem Cells Research
- Viral-associated cancers and disorders
- Autophagy in Disease and Therapy
- Immune cells in cancer
- Histiocytic Disorders and Treatments
- Peptidase Inhibition and Analysis
- Retinal Development and Disorders
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- PI3K/AKT/mTOR signaling in cancer
National Institutes of Health
2013-2024
National Institute of Allergy and Infectious Diseases
2015-2024
Genomics (United Kingdom)
2017
Cleveland Clinic
2017
VA Western New York Healthcare System
2014
University of Wisconsin–Madison
2013
National Wildlife Health Center
2013
Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development targeted therapies.
X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia (XMEN) disease are caused by deficiency of the transporter 1 (MAGT1) gene. We studied 23 patients XMEN, 8 whom were naive. observed lymphadenopathy (LAD), cytopenias, liver disease, cavum septum pellucidum (CSP), increased CD4-CD8-B220-TCRαβ+ T cells (αβDNTs), in addition to previously described features an inverted CD4/CD8 ratio, CD4+ lymphocytopenia, B cells, dysgammaglobulinemia, decreased expression natural...
Effective eradication of leukemic stem cells (LSCs) remains the greatest challenge in treating acute myeloid leukemia (AML). The immune receptor LAIR-1 has been shown to regulate LSC survival; however, therapeutic potential this pathway unexplored. We developed a agonist antibody, NC525, that induced cell death LSCs, but not healthy hematopoietic vitro, and killed LSCs AML blasts both cell- patient-derived xenograft models. showed agonism drives unique apoptotic signaling program was...
Members of the miR-290 family are most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects differentiation, pluripotency, and proliferation ESCs, but molecular program that they control has not been fully delineated. In absence Dicer, ESCs fail to express mature miRNAs have selective aberrant overexpression Hoxa, Hoxb, Hoxc, Hoxd genes essential for body plan patterning during embryogenesis, do undergo a full differentiation program....
<h3>Background</h3> Siglec-15 (S15) is a member of the Siglec family immunoglobulin superfamily proteins involved in immune regulation. NC318 first-in-class humanized IgG1κ monoclonal antibody that blocks S15-mediated suppression. <h3>Methods</h3> The Phase 1 dose-escalation study was classical 3+3 design 15 tumor types (n=49). 2 (n=47) conducted at 400 mg q2w 4 types. Inclusion criteria included subjects with advanced/metastatic solid tumors refractory or resistant to currently available...
Abstract Background Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn ( Ovis canadensis ; BHS) overlaps with states or provinces that have contained scrapie-positive goats areas present epizootics CWD in cervids. No TSEs been documented BHS, but the susceptibility this species to remains unknown. Results We acquired a library BHS tissues found no evidence...
Abstract Elucidating the molecular basis of immunodeficiency diseases is a powerful approach to discovering new immunoregulatory pathways in humans. Here we report 10 affected individuals from 4 families with disease comprising severe progressive lymphopenia, autoimmunity, immunodeficiency, and liver due recessive loss function variants “GTPase immunity-associated proteins” protein 5 (GIMAP5) . We show that involves naïve T lymphocytes corresponding increase antigen-experienced, but poorly...
<h3>Background</h3> Single agent ICIs are ineffective in treating Microsatellite Stable/Microsatellite Instability-Low (MSS/MMI-L) CRC due to the suppressive roles of Tregs, myeloid derived suppressor cells (MDSCs) and tumor microenvironment (TME) with dense collagen forming a barrier that blocks immune cell entry suppresses activation. NC410, dimeric LAIR-2 protein fused human IgG1 Fc domain, targets remodels collagen, enhances infiltration LAIR-1-mediated suppression by preventing binding...
<h3>Background</h3> Collagen and C1q in the extracellular matrix (ECM), are predominant ligands for LAIR-1, an inhibitory receptor expressed on cell surface of several immune subsets that inhibits activation migration. LAIR-2, a soluble homolog competes binding to collagen serves as natural decoy promote function under normal conditions. Dysregulation ECM increased expression within tumor microenvironment (TME) plays critical role promoting progression. NC410 was engineered overcome this...
Studies to understanding interspecies transmission of transmissible spongiform encephalopathies (TSEs, prion diseases) are challenging in that they typically rely upon lengthy and costly vivo animal challenge studies. A number vitro assays have been developed aid measuring species barriers, thereby reducing use providing quicker results than bioassays. Here, we present the protocol for a rapid conversion assay called efficiency ratio (CER) assay. In this cellular protein (PrPC) from an...
Studies to understanding interspecies transmission of transmissible spongiform encephalopathies (TSEs, prion diseases) are challenging in that they typically rely upon lengthy and costly vivo animal challenge studies. A number vitro assays have been developed aid measuring species barriers, thereby reducing use providing quicker results than bioassays. Here, we present the protocol for a rapid conversion assay called efficiency ratio (CER) assay. In this cellular protein (PrPC) from an...
Abstract In this study, we harness Whole Exome Sequencing (WES) to interrogate the underlying genetic cause in a patient cohort suffering from Mendelian disease of immune dysregulation characterized by severe lymphopenia, splenomegaly, anemia, thrombocytopenia and liver failure. Bioinformatic analysis revealed novel mutations small GTPase that led near complete loss mature protein cells. Animal models lacking these genes develop remarkably similar observed human patients, however, molecular...
<h3>Background</h3> The tumor extracellular matrix (ECM) functions as a physical barrier to immune cell infiltration and acts directly inhibit cells by interacting with the inhibitory receptor, Leukocyte Associated Immunoglobulin-Like Receptor-1 (LAIR-1). Several recent publications on pre-clinical studies have demonstrated this inhibition can be reversed NC410, recombinant form of LAIR-2 protein, naturally produced soluble decoy that normally compete LAIR-1 binding. NC410 is composed...
<h3>Background</h3> NC762 is a humanized IgG1κ monoclonal antibody that targets human B7-H4 (B7 homolog 4), transmembrane protein, associated with the B7 family of molecules known for their immunomodulatory functions. While limited expression observed on healthy tissue, commonly expressed by several tumor types including ovarian, lung, renal, melanoma, prostate, pancreatic, and breast cancers often correlated poor clinical outcome. Given differential in cancerous presents itself as an...