A5028031509- DNA and Nucleic Acid Chemistry
- ATP Synthase and ATPases Research
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- T-cell and B-cell Immunology
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Systemic Lupus Erythematosus Research
- Crystallization and Solubility Studies
- Cell death mechanisms and regulation
- X-ray Diffraction in Crystallography
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
- Neuroscience and Neuropharmacology Research
- Crystallography and molecular interactions
- Immune cells in cancer
- CAR-T cell therapy research
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Synthesis and pharmacology of benzodiazepine derivatives
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
Ifm Therapeutics (United States)
2018-2025
Harvard University
1991-2024
University of Michigan
2010-2023
Lycera (United States)
2014-2021
Bellingham Technical College
2016
Michigan United
2001-2016
Data Harbor (United States)
2015
Cornell University
2014
University of Udine
2012
University of Padua
2012
Here we define the molecular nature of mitochondrial permeability transition pore (PTP), a key effector cell death. The PTP is regulated by matrix cyclophilin D (CyPD), which also binds lateral stalk F O 1 ATP synthase. We show that CyPD oligomycin sensitivity-conferring protein subunit enzyme at same site as synthase inhibitor benzodiazepine 423 (Bz-423), Bz-423 sensitizes to Ca 2+ like itself, and decreasing expression RNAi increases sensitivity . Purified dimers synthase, did not contain...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBinding of influenza virus hemagglutinin to analogs its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and x-ray crystallographyNicholas K. Sauter, John E. Hanson, Gary D. Glick, Jerry H. Brown, Robert L. Crowther, Seong Joon Park, J. Skehel, Don C. WileyCite this: Biochemistry 1992, 31, 40, 9609–9621Publication Date (Print):October 13, 1992Publication History Published online1 May 2002Published...
We have engineered aptamers that contain fluorescent reporters and signal the presence of cognate ligands in solution. Two different anti-adenosine "signaling aptamers", one made from RNA DNA, can selectively adenosine Increases fluorescence intensity reproducibly follow increases concentration, be used for quantitation. The facile methods we developed potentially generating a wide variety signaling use sensor arrays.
Bioenergetic properties differentiate alloreactive T cells from other proliferating and can be exploited to arrest GVHD in mice.
The coinhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity graft-versus-host disease (GVHD), but interplay between inhibition metabolism is not well studied. We found that both murine human alloreactive cells concomitantly upregulated expression increased levels reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1(Hi)ROS(Hi) phenotype was...
RORγt is the key transcription factor controlling development and function of CD4+ Th17 CD8+ Tc17 cells. Across a range human tumors, about 15% T cell fraction in tumor-infiltrating lymphocytes are RORγ+ To evaluate role RORγ antitumor immunity, we have identified synthetic, small molecule agonists that selectively activate to greater extent than endogenous agonist desmosterol. These enhance effector Type 17 cells by increasing production cytokines/chemokines such as IL-17A GM-CSF,...
Abstract Integration of signaling and metabolic pathways enables sustains lymphocyte function. Whereas changes occurring during T cell activation are well characterized, the demands differentiated lymphocytes largely unexplored. In this study, we defined bioenergetics Th17 effector cells generated in vivo. These depend on oxidative phosphorylation (OXPHOS) for energy cytokine production. Mechanistically, essential role OXPHOS results from their limited capacity to increase glycolysis...
Infection by influenza virus is initiated a cellular adhesion event that mediated the viral protein, hemagglutinin, which exposed on surface of virion. Hemagglutinin recognizes and binds to cell sialic acid residues. Although each individual ligand binding interaction weak, high affinity for cells bear residues thought result from multivalent attachment process involving many similar recognition events. To evaluate such we have synthesized three series compounds, containing two separated...
Take any partner: Benzodiazepine derivative Bz-423 (see picture) can be described as an indiscriminate solvate former it cocrystallizes with a diverse array of small molecules. This behavior was investigated by analysis the packing efficiency these crystal forms relative to that unsolvated and appropriate model compound. Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z503533_s.pdf or from author. Please note: The publisher not...
Mitochondria of Drosophila melanogaster undergo Ca(2+)-induced Ca(2+) release through a putative channel (mCrC) that has several regulatory features the permeability transition pore (PTP). The PTP is an inner membrane forms from F-ATPase, possessing conductance 500 picosiemens (pS) in mammals and 300 pS yeast. In contrast to PTP, mCrC not permeable sucrose appears be selective for H(+). We show (i) like affected by sense rotation Bz-423, Mg(2+)/ADP; (ii) expression human cyclophilin D...
T-cell activation requires increased ATP and biosynthesis to support proliferation effector function. Most models of are based on in vitro culture systems posit that aerobic glycolysis is employed meet energetic biosynthetic demands. By contrast, T cells activated vivo by alloantigens graft-versus-host disease (GVHD) increase mitochondrial oxygen consumption, fatty acid uptake, oxidation, with small increases glucose uptake glycolysis. Here we show these differences not a consequence...
Background Cellular metabolism plays a critical role in regulating T cell responses and the development of memory cells with long-term protections. However, metabolic phenotype antigen-activated that are responsible for generation long-lived has not been characterized. Design Methods Using lymphocytic choriomeningitis virus (LCMV) peptide gp33-specific CD8+ derived from receptor transgenic mice, we characterized proliferating were activated expanded vitro presence or absence rapamycin,...
The oligomycin-sensitivity conferring protein (OSCP) of the mitochondrial F(O)F1 ATP synthase has long been recognized to be essential for coupling proton transport synthesis. Located on top catalytic F1 sector, it makes stable contacts with both and peripheral stalk, ensuring structural functional between F(O) F1, which is disrupted by antibiotic, oligomycin. Recent data have established that OSCP binding target cyclophilin (CyP) D, a well-characterized inducer permeability transition pore...
Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation Th17 differentiation and function. was initially identified as a transcription factor required for thymopoiesis by maintaining survival CD4+CD8+ (DP) thymocytes. While RORγ antagonists are currently being developed to treat autoimmunity, it remains unclear how inhibition may impact thymocyte development. In this study, we show that in addition regulating DP thymocytes survival, also controls genes...
X-ray crystal structures have been determined for several complexes between influenza virus hemagglutinin and derivatives of its cell-surface receptor, sialic acid (Neu5Ac). Difference electron density maps establish the existence a second binding site in addition to primary characterized previously. Three compounds bind both sites: Neu5Ac(alpha 2-3)Gal(beta 1-4)Glc [(alpha 2-3)sialyllactose], alpha-2-O-(4'-benzylamidocarboxybutyl)-5-N-acetylneuraminic acid,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular recognition of bivalent sialosides by influenza virusGary D. Glick and Jeremy R. KnowlesCite this: J. Am. Chem. Soc. 1991, 113, 12, 4701–4703Publication Date (Print):June 1, 1991Publication History Published online1 May 2002Published inissue 1 June 1991https://pubs.acs.org/doi/10.1021/ja00012a060https://doi.org/10.1021/ja00012a060research-articleACS PublicationsRequest reuse permissionsArticle Views286Altmetric-Citations63LEARN ABOUT...
The specific structural features of 24 N-acetylneuraminic acid derivatives required for the high affinity interaction sialoglycoconjugates with sialic acidspecific lectin from slug Limax Aavus were studied by hapten inhibition precipitation.These results provide insight regarding structure binding pocket that exists in L. tlauus agglutinin (LFA).The a-anomer is a very important factor to lectin.The carboxylic group makes only moderate contribution binding, since modifications decrease...