- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- T-cell and Retrovirus Studies
- Synthesis of heterocyclic compounds
- Asthma and respiratory diseases
- Asymmetric Synthesis and Catalysis
- Monoclonal and Polyclonal Antibodies Research
- Protein Kinase Regulation and GTPase Signaling
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Phenothiazines and Benzothiazines Synthesis and Activities
- Antimicrobial Peptides and Activities
- Retinal Development and Disorders
- Urticaria and Related Conditions
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Glaucoma and retinal disorders
- Fungal Infections and Studies
- Protease and Inhibitor Mechanisms
- Diet and metabolism studies
National Institutes of Health
2002-2025
National Institute of Diabetes and Digestive and Kidney Diseases
2025
Takeda (United States)
2023
Merck Serono (Italy)
2016
Merck (Germany)
2016
Stanford University
2010-2014
University of Münster
2011-2013
National Eye Institute
2006
Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional protein belonging to the serpin superfamily with demonstrable neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We have previously provided biochemical evidence for high affinity PEDF-binding sites proteins in plasma membranes of retina, retinoblastoma, CNS cells. This study was designed reveal a receptor involved biological activities PEDF. Using yeast two-hybrid screening,...
Pigment epithelium-derived factor (PEDF), a neurotrophic and antiangiogenic serpin, is identified in tissues rich collagen, e.g. cornea, vitreous, bone, cartilage. We show that recombinant human PEDF formed complexes with collagens from the bovine cornea vitreous. have examined direct binding of to collagen I found interactions were ionic nature occurred when both solution, either one was immobilized, or even denatured under reducing conditions. 125I-PEDF bound immobilized saturable fashion...
Tumor-associated macrophages (TAM) play an important role in maintaining the immunosuppressive state of tumor microenvironment (TME). High levels CD163+ TAMs specifically are associated with poor prognosis many solid types. Targeting may represent a key approach development next generation cancer immune therapeutics. Members leukocyte immunoglobulin-like receptor B (LILRB) family, including LILRB2 (ILT4), known to transmit inhibitory signals and other myeloid cells. Leveraging bulk single...
To explore the hydrophobic binding region of σ1 receptor protein, regioisomeric spirocyclic thiophenes 9–11 were developed as versatile building blocks. Regioselective α- and β-arylation using catalyst systems PdCl2/bipy/Ag2CO3 PdCl2/P[OCH(CF3)2]3/Ag2CO3 allowed introduction various aryl moieties at different positions in last step synthesis. The increasing affinity order 4 < 5/6 7/8 indicates that additional moiety S atom thiophene control affinity. main features pharmacophore model for...
Abstract Activation of PLCβ enzymes by G iβγ and αq/11 proteins is a common mechanism to trigger cytosolic Ca 2+ increase. We others reported that inhibitor FR900359 (FR) can inhibit both αq - and, surprisingly, -mediated intracellular mobilization. Thus, the αi -G βγ -PLCβ-Ca signaling axis depends entirely on presence active , which reasonably explained FR-inhibited -induced release. However, conclusion controlled derives mostly from HEK293 cells. Here we show indeed in cells siRNA...
Summary Allergy to the house dust mite Dermatophagoides pteronyssinus is mediated by IgE major allergens Der p I and II in majority of mite‐allergic patients. In recent years, standardized preparations D. , commercially available from several sources, have become widely used for diagnosis immunotherapy allergy. As standardization implies uniformity allergen composition potency, we directly compared absolute relative quantities six different commercial extracts . Our findings reveal...
<b>Background: </b>There is increasing evidence that IgE–mediated reactivity against autoantigens could play a role in the pathology of severe chronic atopic diseases. <b>Methods: </b>Human mitochondrial managenese superoxide dismutase (MnSOD), acidic ribosomal P<sub>2</sub> protein and cyclophilins were cloned by PCR, expressed as inclusion body proteins <i>Escherichia coli</i>, purified Ni<sup>2+</sup>–chelate affinity...
The hypothesis that the σ1receptor will tolerate an additional aryl moiety in position 1 of spirocyclic system was based on pyrazole derivatives, pharmacophore models ligands and DFT calculations. strategy introducing residue at final step synthesis allowed preparation a large set diverse for exploitation hydrophobic pocket protein. catalyst PdCl2/2,2′-bipyridyl/Ag2CO3 is able to introduce various groups onto α-positions thiophene derivatives 5 6 afford target aryl-appended thiophenes 3 4....
The ability to recognize small organic molecules and chemical modifications of host is an essential capability the adaptive immune system, which until now was thought be mediated mainly by B cell antigen receptors. Here we report that molecules, such as cyanine 3 (Cy3), a synthetic fluorescent molecule, 4-hydroxy-3-nitrophenylacetyl (NP), one most noted haptens, are γδ T antigens, recognized directly specific TCRs. Immunization with Cy3 conjugates induces rapid Cy3-specific IL-17 response....
Abstract Direct C–H bond arylation in the α‐ and β‐positions of spirocyclic thiophenes containing various functional groups (amine, ether, acetal, lactone) was accomplished. Selective phenylation α‐position thiophene ring achieved by using catalytic system PdCl 2 /bipy/Ag CO 3 . The introduction phenyl moieties to β‐position performed with /P[OCH(CF ) ] /Ag Even five‐membered lactone 10 an electron‐withdrawing carbonyl moiety directly attached arylated. Spirocyclic substituted a position A...
The production of specific IgE, which underlies the allergic response, may be a normal correlate immune response to certain class antigen (allergens), or could represent unique driven by regulatory signals that are absent in non-allergic individuals. If atopic subjects do possess environment favoring IgE production, they display not only allergen-specific but also higher levels total and frequencies IgE-producing B lymphocytes.To address contribution antibody-producing cell number...
<title>Abstract</title> Activation of PLCβ enzymes by G<sub>iβγ</sub> and G<sub>αq/11</sub> proteins is a common mechanism to trigger cytosolic Ca<sup>2+</sup> increase. We others reported that inhibitor FR900358 (FR) can inhibit both G<sub>αq</sub>- and, surprisingly, G<sub>iβγ</sub>-mediated intracellular mobilization. Thus, the G<sub>αi</sub>-G<sub>βγ</sub>-PLCβ-Ca<sup>2+</sup> signaling axis depends entirely on presence active G<sub>αq</sub>, which reasonably explained FR-inhibited...
PEDF is an extracellular multifunctional protein with demonstrable neurotrophic, antiangiogenic and antitumorigenic properties, affinity for collagens cell-surface receptors. Using bioinformatic tools we examined the sequence of a novel gene from human retinal pigment epithelium (PEDF-R) to reveal role as receptor. ENSEMBLE searches showed that PEDF-R maps locus 11p15.5 on chromosome 11. BLASTn revealed putative homologues in other species. fragments were found various organs, RT-PCR...
A 48-year-old Caucasian woman with history of multiple sclerosis (MS) presented erythematous papulonodular lesions in her extremities and trunk. She was being treated glatiramer acetate (GA) for the past 10 years glatiramoid, Glatopa, 2 prior to this presentation. skin biopsy showed CD30 + lymphoproliferative disorder consistent lymphomatoid papulosis (LyP). Three weeks after stopping were improved. It remains unclear whether GA’s or Glatopa’s capability alter T-cell differentiation, may...
<p>Sensitivity of LILRB2 as a predictive biomarker for pharmacodynamic response measured by the macrophage polarization score in histoculture explant cultures.</p>
<p>Example gating strategy for blood monocytes</p>
<p>Example gating strategy in vitro differentiated GM-CSF and IL-4 Dendritic Cells</p>
<p>Changes in gene expression by JTX-8064 both macrophages and dendritic cells 6 days on treatment during differentiation</p>
<p>Example gating strategy in vitro differentiated M-CSF macrophages</p>