A5038979649- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Viral Infectious Diseases and Gene Expression in Insects
- Galectins and Cancer Biology
- Virus-based gene therapy research
- Pneumocystis jirovecii pneumonia detection and treatment
- Reproductive tract infections research
- T-cell and Retrovirus Studies
- CRISPR and Genetic Engineering
- Reproductive System and Pregnancy
- Inflammasome and immune disorders
- Immunodeficiency and Autoimmune Disorders
- Gut microbiota and health
- Tryptophan and brain disorders
- RNA Interference and Gene Delivery
- Pregnancy and preeclampsia studies
- Preterm Birth and Chorioamnionitis
- Lymphoma Diagnosis and Treatment
- Atherosclerosis and Cardiovascular Diseases
- Gender Diversity and Inequality
Yale University
2011-2024
Yale Cancer Center
2017-2018
University of New Haven
2018
Laboratory of Molecular Genetics
1999-2008
Isfahan University of Medical Sciences
2008
Mount Sinai Medical Center
2002
Pfizer (United States)
1993
Salk Institute for Biological Studies
1990
Stanford University
1981-1988
University of Wisconsin–Madison
1980-1986
Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are poorly understood. We leveraged a collection 14 ICI-resistant lung cancer samples investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play role PD-1 PD-L1 antagonistic antibodies. Recurrent mutations copy-number changes were not detected our cohort. In one case, we found homozygous loss B2M that caused lack cell-surface...
The biological determinants of sensitivity and resistance to immune checkpoint blockers are not completely understood. To elucidate the role intratumoral T-cells their association with tumor genomic landscape, we perform paired whole exome DNA sequencing multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients treated PD-1 axis blockers. QIF is used simultaneously measure level CD3+ infiltrating lymphocytes (TILs), situ...
Abstract Lipids can be of endogenous or exogenous origin and affect diverse biological functions, including cell membrane maintenance, energy management cellular signalling. Here, we report >800 lipid species, many which are associated with health-to-disease transitions in diabetes, ageing inflammation, as well cytokine–lipidome networks. We performed comprehensive longitudinal lipidomic profiling analysed >1,500 plasma samples from 112 participants followed for up to 9 years (average...
To understand the dynamic interplay between human microbiome and host during health disease, we analyzed microbial composition, temporal dynamics, associations with multi-omics, immune, clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that stability individuality are body-site specific heavily influenced by host. The stool oral more stable than skin nasal microbiomes, possibly due to their interaction environment. identify individual-specific...
Gamma rays from a cesium source were used to generate human lymphoblastoid cell line variants that had lost expression of all major histocompatibility complex antigens coded for by single haplotype. The was heterozygous at the glyoxalase I locus and HLA haplotypes HLA-A1, B8, DRw3, HLA-A2, B5, DRw1. We selected with anti-HLA-B8 antiserum in population cells been irradiated 300 R. incidence B8-loss 4.1 X 10(-5) on day 5 after irradiation. Analysis showed expressions GLO alleles trans B8...
We report that the cytoplasmic domains of T-lymphocyte glycoproteins CD4 and CD8 alpha contain short related amino acid sequences are involved in binding amino-terminal domain intracellular tyrosine protein kinase, p56lck. Transfer as few six residues from to an unrelated conferred p56lck hybrid HeLa cells. The common sequence motif shared by contains two cysteines, mutation either cysteine eliminated p56lck.p56lck also within its CD4-CD8 alpha-binding domain, both critical interaction with...
We isolated stable transformants of mouse L cells expressing human cell surface differentiation antigens by using immunofluorescence with monoclonal antibodies and selection a fluorescence-activated sorter (FACS). Mouse (TK-) were cotransformed cellular DNA the herpes simplex virus thymidine kinase (TK) gene. TK+ first selected. The populations stained various fluorescent to membrane antigens, positive sorted cloned FACS. Transformants for HLA class I beta 2-microglobulin, T-cell Leu-1 Leu-2...
Citation Mulla MJ, Myrtolli K, Potter J, Boeras C, Kavathas PB, Sfakianaki AK, Tadesse S, Norwitz ER, Guller Abrahams VM. Uric acid induces trophoblast IL-1β production via the inflammasome: implications for pathogenesis of preeclampsia. Am J Reprod Immunol 2010; 65: 542–548 Problem Preeclampsia is associated with hyperuricemia, which correlates disease severity. Levels circulating uric increase before clinical manifestations, suggesting that they may be causally related. acid, or monosodium...
Efficient transfection and expression of cDNA libraries in human cells has been achieved with an Epstein-Barr virus-based subcloning vector (EBO-pcD). The plasmid contains a resistance marker for hygromycin B to permit selection transformed cells. virus origin replication (oriP) the nuclear antigen gene have also incorporated into ensure that plasmids are maintained stably extrachromosomally. Human lymphoblastoid can be at high efficiency (10 15%) by such plasmids, thereby permitting ready...
We report that the cytoplasmic domains of T-lymphocyte glycoproteins CD4 and CD8 alpha contain short related amino acid sequences are involved in binding amino-terminal domain intracellular tyrosine protein kinase, p56lck. Transfer as few six residues from to an unrelated conferred p56lck hybrid HeLa cells. The common sequence motif shared by contains two cysteines, mutation either cysteine eliminated p56lck.p56lck also within its CD4-CD8 alpha-binding domain, both critical interaction with...
Expression of the human CD8 alpha gene is restricted to cells lymphoid lineage and developmentally regulated during thymopoiesis. As an initial step towards understanding molecular basis for tissue-specific expression this gene, we surveyed surrounding chromatin structure potential cis-acting regulatory regions by DNase I hypersensitivity mapping found four hypersensitive sites, three which were T cell restricted. By using a reporter-based approach, T-cell-specific enhancer was identified...
The lymphocyte differentiation marker CD8 acts as a coreceptor with the T cell receptor (TCR) during recognition of peptide presented by major histocompatibility complex (MHC) class I molecules. functions in TCR are thought to be signaling through association protein tyrosine kinase p56lck and adhesion MHC alpha 3 domain. While ability alpha/alpha homodimer bind classical molecules has been shown, it is unclear whether can also nonclassical Of particular interest human leukocyte antigen...
Abstract Macrophage migration inhibitory factor (MIF) is a leaderless protein that secreted from cells by specialized, nonclassical export pathway. The release of MIF nevertheless regulated and its production in response to different inflammatory, mitogenic, hormonal stimuli plays an important role diverse physiologic pathologic processes. We report herein the identification Golgi complex-associated p115 as intracellular binding partner for MIF. interacts with cytoplasm stimulated secretion...
We report the isolation of genomic and cDNA clones encoding human T-lymphocyte cell-surface differentiation antigen, Leu-2 (T8), by use a combination transfection, fluorescence-activated cell-sorting, subtractive hybridization. constructed library with mRNA from mouse L-cell transfectant in which gene is expressed amplified. identified screening selected probe second amplified transfectant. This contained species not removed hybridization mRNA. A clone was used to isolate clone. Transfection...
Women with antiphospholipid syndrome (APS) are at risk of recurrent pregnancy loss and obstetrical disorders, such as preeclampsia intrauterine growth restriction (IUGR). Antiphospholipid antibodies (aPL) directly target the placenta by binding beta2-glycoprotein I (β2GPI) expressed on trophoblast. We recently demonstrated in human first trimester trophoblast cells that anti-β2GPI (Abs) induce secretion IL-1β a Toll-like receptor 4 (TLR4)-dependent manner. requires processing pro-IL-1β this...
The sequence of Lyt-2 cDNA shows that it is a new member the immunoglobulin super gene family. Analysis predicted amino acid indicates polypeptide synthesized with 27-amino leader, and mature protein has an variable region (Ig V)-related approximately 100 acids, extracellular spacer 43, transmembrane 38, intracytoplasmic 27 acids. its human analogue Leu-2 are 56% homologous; analysis Ig V-related domains two molecules have evolved away from each other faster than carboxyl-terminal half proteins.
The intracellular survival of the bacterial pathogen Chlamydia trachomatis depends on protein synthesis by microbe soon after internalization. Pharmacologic inhibition translation inhibits early trafficking parasitophorous vacuole (inclusion) to microtubule-organizing center (MTOC) and promotes its fusion with lysosomes, which is normally blocked Chlamydia. Depletion cellular tryptophan pools gamma interferon-inducible indoleamine-2,3-dioxygenase (IDO) believed be major innate immune...
The cell surface glycoprotein CD8 functions as a coreceptor with the TCR on cytotoxic T lymphocytes. Mutational analysis of binding site for MHC class I predicted that distinct surfaces would interact both alpha 2 and 3 domains I. Using cell-cell adhesion assay, we identified three residues Q115, D122, E128 in domain critical interaction CD8. side chains these point towards cavity formed by 1/alpha platform, beta 2-microglobulin (beta 2m) These were to contact based bivalent model between...
Abstract CD8 engagement is believed to be a critical event in the activation of naive T cells. In this communication, we address effects peptide-MHC (pMHC)/TCR affinity on necessity cell primary Using two peptides with different measured avidities for same pMHC-TCR complex, compared biochemical pMHC/TCR and surface binding avidity without engagement. We early signaling events later functional activity cells manner. Although are altered, find that high-affinity interactions can overcome need...