Paul Spiegel

ORCID: 0000-0001-7982-5424
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About
Contact & Profiles
Research Areas
  • Superconducting Materials and Applications
  • Atomic and Subatomic Physics Research
  • Hemophilia Treatment and Research
  • Blood Coagulation and Thrombosis Mechanisms
  • Platelet Disorders and Treatments
  • Blood properties and coagulation
  • Monoclonal and Polyclonal Antibodies Research
  • Coagulation, Bradykinin, Polyphosphates, and Angioedema
  • RNA and protein synthesis mechanisms
  • Phagocytosis and Immune Regulation
  • RNA modifications and cancer
  • Erythrocyte Function and Pathophysiology
  • Bioactive natural compounds
  • RNA Research and Splicing
  • Protein purification and stability
  • Phytochemical compounds biological activities
  • Bacterial Genetics and Biotechnology
  • Peptidase Inhibition and Analysis
  • DNA and Nucleic Acid Chemistry
  • CAR-T cell therapy research
  • Heparin-Induced Thrombocytopenia and Thrombosis
  • Lipid Membrane Structure and Behavior
  • Nanoparticle-Based Drug Delivery
  • Traditional and Medicinal Uses of Annonaceae
  • Muscle activation and electromyography studies

Western Washington University
2014-2025

Bellingham Technical College
2019

Fred Hutch Cancer Center
2001-2007

University of California, Santa Cruz
2007

North Seattle College
2006

University of Washington
2001-2006

KU Leuven
2001

Following peptide bond formation, transfer RNAs (tRNAs) and messenger RNA (mRNA) are translocated through the ribosome, a process catalyzed by elongation factor EF-G. Here, we have used combination of chemical footprinting, peptidyl transferase activity assays, mRNA toeprinting to monitor effects EF-G on positions tRNA relative A, P, E sites ribosome in presence GTP, GDP, GDPNP, fusidic acid. Chemical footprinting experiments show that binding non-hydrolyzable GTP analog GDPNP or GDP.fusidic...

10.1261/rna.601507 article EN RNA 2007-07-13

We determined the crystal structure of a bifunctional group I intron splicing factor and homing endonuclease, termed -Ani maturase, in complex with its DNA target at 2.6 Å resolution. The demonstrates remarkable structural conservation β-sheet DNA-binding motif between highly divergent enzyme subfamilies. recognition by I- Ani was further studied using nucleoside deletion DMS modification interference analyses. Correlation these results provides information on relative importance individual...

10.1101/gad.1109003 article EN Genes & Development 2003-01-01

Thiostrepton, a macrocyclic thiopeptide antibiotic, inhibits prokaryotic translation by interfering with the function of elongation factor G (EF-G). Here, we have used 70S ribosome binding and GTP hydrolysis assays to study effects thiostrepton on EF-G newly described factor, 4 (EF4). In presence thiostrepton, ribosome-dependent is inhibited for both EF4, IC(50) values equivalent concentration (0.15 µM). Further studies indicate mode inhibition abrogate stable EF4 ribosome. support this...

10.1093/nar/gkr623 article EN cc-by-nc Nucleic Acids Research 2011-09-09

During the blood coagulation cascade, factor VIII (FVIII) is activated by thrombin to form (FVIIIa). FVIIIa associates with platelet surfaces at site of vascular damage an intrinsic tenase complex IX. A working model for FVIII membrane binding involves association positively charged residues negatively lipid headgroups and burial hydrophobic into interior. Currently, atomic details interactions orientation are lacking. This study reports residue-specific C domain...

10.1021/acs.jpcb.4c06575 article EN cc-by The Journal of Physical Chemistry B 2025-01-22

Haemophilia A is a chronic life-threatening condition caused by deficiency or dysfunction of plasma coagulation factor VIII (FVIII) and commonly managed prophylaxis with regular infusion FVIII protein. major obstacle to replacement therapy the generation alloantibodies that diminish efficacy. Disulfide bonds link pairs cysteine residues in proteins several have been found be only partially formed mature proteins. contains 8 disulfide their redox state human blood recombinant was determined...

10.1182/bloodadvances.2025016474 article EN cc-by-nc-nd Blood Advances 2025-04-09

The intrinsic tenase (Xase) complex, formed by factors (f) VIIIa and fIXa, forms on activated platelet surfaces catalyzes the activation of factor X to Xa, stimulating thrombin production in blood coagulation cascade. structural organization membrane-bound Xase complex remains largely unknown, hindering our understanding underpinnings that guide assembly. Here, we aimed characterize bound a lipid nanodisc with biolayer interferometry (BLI), Michaelis-Menten kinetics, small-angle X-ray...

10.1182/bloodadvances.2021005874 article EN cc-by-nc-nd Blood Advances 2022-03-08

A convergent synthesis of a C<sub>1</sub>–C<sub>23</sub> fragment the archa­zolids has been completed based on high-yielding Stille coupling to construct substituted <i>Z</i>,<i>Z</i>,<i>E</i>-conjugated triene. After removal protecting groups, resulting tetrol exhibited evidence for inhibition vacuolar-type ATPase (V-ATPase) but not cyclooxygenase (COX) inhibitory activity.

10.1055/s-0036-1588413 article EN Synlett 2017-02-08

The development of pathogenic antibody inhibitors against coagulation factor VIII (FVIII) occurs in approximately 30% congenital hemophilia A patients receiving FVIII replacement therapy as well all cases acquired A. KM33 is an anti-C1 domain inhibitor previously isolated from a severe patient. In addition to potently blocking binding von Willebrand and phospholipid surfaces, disrupts lipoprotein receptor-related protein 1 (LRP1), which drives hepatic clearance antigen presentation dendritic...

10.1182/blood.2023020181 article EN cc-by-nc-nd Blood 2023-05-16

Myofibrillar Ca sensitivity and single-channel acetylcholine receptor (AChR) currents were studied in garter snake (Thamnophis sirtalis sirtalis) costocutaneous muscle fibers. Nomarski optics used to identify tonic fast- slow-twitch Measurements of tension generation made using chemically skinned The maximum tensions the three types fibers similar, had similar sensitivities. Compared with twitch fibers, lower threshold concentrations for a larger range between tension. AChR channels by...

10.1152/ajpcell.1990.259.6.c911 article EN AJP Cell Physiology 1990-12-01
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