A5036296799- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Bladder and Urothelial Cancer Treatments
- T-cell and B-cell Immunology
- Multiple and Secondary Primary Cancers
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Urinary and Genital Oncology Studies
- Cancer therapeutics and mechanisms
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Treatment and Research
- Protein purification and stability
- Pancreatic and Hepatic Oncology Research
- Multiple Myeloma Research and Treatments
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- RNA Interference and Gene Delivery
- Synthesis and Biological Evaluation
Fox Chase Cancer Center
2016-2025
Temple University
2018-2024
Temple University Health System
2022-2023
McDaniel College
2017
University of Maryland, Baltimore
2013-2014
Philadelphia University
2012
National Cancer Institute
2010
Creighton University
2010
Fugro (Norway)
2008
Radboud University Nijmegen
2007
Natural killer (NK) cells are known to play a role in mediating innate immunity, enhancing adaptive immune responses, and have been implicated anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) by reactivity of CD16 with the Fc region human IgG1 antibodies. The NK-92 cell line, derived from lymphoma patient, has previously well characterized adoptive transfer irradiated demonstrated safety shown preliminary evidence clinical benefit cancer patients. devoid CD16,...
Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate and lacks effective therapeutics. Therefore, it is of paramount importance to identify new targets. Using multiplex data from patient tissue, three-dimensional coculturing in vitro assays, orthotopic murine models, we identified Netrin G1 (NetG1) as promoter PDAC tumorigenesis. We found that NetG1+ cancer-associated fibroblasts (CAF) support survival, through NetG1-mediated effect on glutamate/glutamine metabolism. Also,...
Abstract Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as “viral mimicry,” has emerged an effective strategy to convert immunologically “cold” tumors into “hot.” Through curated CRISPR-based screen of RNA helicases, we identified DExD/H-box helicase 9 (DHX9) potent repressor double-stranded (dsRNA) small cell lung cancers (SCLC). Depletion DHX9 induced accumulation dsRNA and triggered tumor-intrinsic immunity. Intriguingly,...
The B cell antigen receptor complex is a hetero-oligomeric structure composed of binding, membrane immunoglobulin, and transducer-transporter substructures. substructure disulfide-linked dimers immunoglobulin (Ig)-α Ig-β/γ subunits that are products the mb-1(α) B29 (β/γ) genes. Although associates with Src family kinases activated after ligation, site interaction these other cytoplasmic effector molecules unknown. tails Ig-α Ig-β chains were found to associate distinct sets molecules. chain...
CD45 is a member of family membrane proteins that possess phosphotyrosine phosphatase activity, and the source much tyrosine activity in lymphocytes. In view its enzymatic high copy number, it seems likely functions transmembrane signal transduction by lymphocyte receptors are coupled to activation kinases. The B cell antigen receptor was found transduce Ca2+-mobilizing only if cells expressed CD45. Also, both immunoglobulin M (mIgM) were lost from surface treated with antibody CD45,...
Natural killer (NK) cells express inhibitory receptors that mediate negative regulation of NK cell cytotoxicity upon binding to MHC class I molecules on target cells. Unrelated B have recently been shown function through recruitment phosphotyrosine phosphatase 1C (PTP-1C). Here, we show a human receptor specific for HLA-C also recruits PTP-1C after phosphorylation induced either by the pharmacological agent phenylarsine oxide or conjugation with This is mediated cytoplasmic...
NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is only natural cytotoxicity that expressed exclusively by primate cells, yet its cellular ligands remain largely unknown. Proliferating cell nuclear Ag (PCNA) overexpressed cancer cells. In this study, we show recognizes PCNA. Their interaction inhibits function through NKp44/ITIM. physical of and PCNA enabled recruitment target immunological synapse. We demonstrate promotes survival...
Abstract Human NK cells lyse Ab-coated target through the process of Ab-dependent cellular cytotoxicity (ADCC). Improving ADCC responses is desirable because it thought to be an important antitumor mechanism for some Abs. cell inhibitory receptors, such as killer Ig-like engage with MHC class I molecules on self-cells block activation. Accordingly, we enhanced by blocking thus perturbing induction self-recognition signal. In a line model anti-lymphoma therapy, combination rituximab Ab that...
Programmed death-1 (PD-1) receptor is an inhibitory on hematopoietic cells that can negatively regulate immune responses, particularly responses to tumors, which often upregulate PD-1 ligands. PD-1/PD-1 ligand blocking antibodies reverse the inhibition and show significant therapeutic promise in treating renal cell carcinoma (RCC), lung cancer, melanoma. While expression tumor-infiltrating lymphocytes has been associated with poor outcome RCC, we sought define biomarkers, including PD-1,...
The Fc receptor on NK cells, FcγRIIIA (CD16), has been extensively studied for its role in mediating antibody-dependent cellular cytotoxicity (ADCC). A homozygous missense mutation CD16 (encoding a L66H substitution) is associated with severe herpesvirus infections rare patients. Here, we identified new patient this and compared the patient's cells to those of originally reported patient. Patients had intact ADCC, but deficient spontaneous cell decreased surface expression CD2, coactivation...
Dengue virus (DV) and West Nile (WNV) have become a global concern due to their widespread distribution ability cause variety of human diseases. Antiviral immune defenses involve NK cells. In the present study, we investigated interaction between cells these two flaviviruses. We show that NK-activating receptor NKp44 is involved in virally mediated activation through direct with flavivirus envelope protein. Recombinant directly binds purified DV WNV proteins specifically domain III protein;...
We have developed 3D-tumoroids and tumor slice in vitro culture systems from surgical specimens derived patients with colorectal cancer (CRC) or lung to evaluate immune cell populations infiltrating cultured tissues. The system incorporates patient's peripherally tumor-derived cells into tumoroid cultures the ability of mimic an immunosuppressive microenvironment (ITM). This enables analysis response standard therapy within weeks resection. Here we show that a CRC patient are highly...
Accumulating evidence demonstrates important roles for natural killer (NK) cells in controlling multiple myeloma (MM). A prospective flow cytometry-based analysis of NK the blood and bone marrow (BM) MM patient subgroups was performed (smoldering (SMM), newly diagnosed (ND), relapsed/refractory, (RR) post-stem cell transplantation (pSCT)). Assessments included biomarker expression function cells, correlations between receptors on with their ligands comparisons healthy controls. The most...
Abstract Purpose: On the basis of preclinical evidence epigenetic contribution to sensitivity and resistance immune checkpoint inhibitors (ICI), we hypothesized that guadecitabine (hypomethylating agent) atezolizumab [anti–programmed cell death ligand 1 (PD-L1)] together would potentiate a clinical response in patients with metastatic urothelial carcinoma (UC) unresponsive initial blockade therapy. Patients Methods: We designed single arm phase II study (NCT03179943) safety run-in identify...
Abstract Killer cell Ig-like receptor (KIR)2DL4 (2DL4, CD158d) was previously described as the only KIR expressed by every human NK cell. It is also structurally atypical among KIRs because it possesses a basic transmembrane residue, which characteristic of many activating receptors, but contains cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM). We epitope-tagged 2DL4 in an NK-like line to study function. Three distinct cDNA clones were analyzed: one encoding “conventional”...
Membrane immunoglobulin M (mIgM) and mIgD are major B-lymphocyte antigen receptors, which function by internalizing antigens for processing presentation to T cells transducing essential signals proliferation differentiation. Although ligation of mIgM or results in rapid activation a phospholipase C tyrosine kinase(s), these receptors have cytoplasmic tails only three amino acid residues (Lys-Val-Lys), seem ill suited direct physical coupling with signal transduction structures. In this...