A5026146363- Muscle Physiology and Disorders
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- SARS-CoV-2 and COVID-19 Research
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Blood Coagulation and Thrombosis Mechanisms
- COVID-19 Clinical Research Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Biochemical and Molecular Research
- 3D Printing in Biomedical Research
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Immunodeficiency and Autoimmune Disorders
- Pharmacological Effects of Natural Compounds
- Tissue Engineering and Regenerative Medicine
- Dietary Effects on Health
- Protein purification and stability
- Acute Kidney Injury Research
- Genetics, Aging, and Longevity in Model Organisms
- Long-Term Effects of COVID-19
- Proteoglycans and glycosaminoglycans research
- TGF-β signaling in diseases
- Analytical Chemistry and Chromatography
Eli Lilly (United States)
2003-2022
Foundation for Applied Molecular Evolution
2008-2012
Indiana University – Purdue University Indianapolis
2009-2012
Indiana University School of Medicine
2009
Richard L. Roudebush VA Medical Center
2009
Protein Express (United States)
2003
Seattle University
1998
University of Washington
1997-1998
Pennsylvania State University
1994-1995
Biotechnology Institute
1995
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies key class of therapeutics that may bridge widespread vaccination campaigns offer treatment solution in populations less responsive to vaccination. Here, we report high-throughput microfluidic screening antigen-specific B cells led the identification LY-CoV555 (also known as bamlanivimab), potent anti-spike...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants concern (VOCs) have negatively affected therapeutic use some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), highly potent spike glycoprotein receptor binding domain (RBD)-specific antibody. potently neutralizes...
SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification LY-CoV555, potent anti-spike neutralizing antibody from convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding receptor-binding domain, ACE2 inhibition, activity. In rhesus macaque challenge model, prophylaxis doses as low 2.5...
BACKGROUND Bebtelovimab is a potent, fully human IgG1 monoclonal antibody (mAb) targeting the S-protein of SARS-CoV-2, with broad neutralizing activity to all currently known SARS-CoV-2 variants concern, including omicron variant lineages. Specialized developmental approaches accelerated initiation clinical trial designed evaluate efficacy and safety bebtelovimab alone (BEB) or together bamlanivimab (BAM) etesevimab (ETE) delivered via slow intravenous push for treatment mild-to-moderate...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProbing the Folding Mechanism of a Leucine Zipper Peptide by Stopped-Flow Circular Dichroism SpectroscopyJill A. Zitzewitz, Osman Bilsel, Jiabin Luo, Bryan E. Jones, and C. Robert MatthewsCite this: Biochemistry 1995, 34, 39, 12812–12819Publication Date (Print):October 3, 1995Publication History Published online1 May 2002Published inissue 3 October...
Catabolite repression of a number catabolic operons in bacilli is mediated by the catabolite control protein CcpA, phosphocarrier HPr from phosphoenolpyruvate-dependent sugar transport system (PTS), and cis-acting DNA sequence termed catabolite-responsive element (cre). We present evidence that CcpA interacts with phosphorylated at Ser46 (Ser(P) HPr) these proteins form specific ternary complex cre DNA. Titration experiments following circular dichroism signal indicate this consists two...
Altered coagulation and inflammation contribute to the pathogenesis of ischemic renal injury. Thrombomodulin is a necessary factor in anticoagulant protein C pathway has inherent anti-inflammatory properties. We studied effect soluble thrombomodulin (sTM) hypoperfusion model kidney To markedly reduce infrarenal aortic blood flow femoral arterial pressures, we clamped suprarenal aorta rats, occluding them 90%, for 60 min. Reversible acute injury (AKI) occurred at 24 h rats subjected...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA reexamination of the folding mechanism dihydrofolate reductase from Escherichia coli: Verification and refinement a four-channel modelPatricia A. Jennings, Bryan E. Finn, Jones, C. Robert MatthewsCite this: Biochemistry 1993, 32, 14, 3783–3789Publication Date (Print):April 13, 1993Publication History Published online1 May 2002Published inissue 13 April...
We describe a bispecific dual-antagonist antibody against human B cell activating factor (BAFF) and interleukin 17A (IL-17). An anti-IL-17 single-chain variable fragment (scFv) derived from ixekizumab (Taltz®) was fused via glycine-rich linker to anti-BAFF tabalumab. The IgG-scFv bound both BAFF IL-17 simultaneously with identical stoichiometry as the parental mAbs. Stability studies of initial revealed chemical degradation aggregation not observed in either antibody. scFv showed high...
Abstract The kinetic folding mechanism for Escherichia coli dihydrofolate reductase postulates two distinct types of transient intermediates. first forms within 5 ms and has substantial secondary structure but little stability. second is a set four species that appear over the course several hundred milliseconds have structure, specific tertiary significant stability (Jennings PA, Finn BE, Jones Matthews CR, 1993, Biochemistry 52 :3783–3789). Pulse labeling hydrogen exchange experiments were...
Administration of activated protein C (APC) protects from renal dysfunction, but the underlying mechanism is unknown. APC exerts both antithrombotic and cytoprotective properties, latter via modulation protease-activated receptor-1 (PAR-1) signaling. We generated variants to study relative importance two functions in a model LPS-induced microvascular dysfunction. Compared with wild-type APC, K193E variant exhibited impaired anticoagulant activity retained ability mediate PAR-1-dependent In...
Poor solubility is a common challenge encountered during the development of high concentration monoclonal antibody (mAb) formulations, but there are currently no methods that can provide predictive information on high-concentration behavior mAbs in early discovery. We explored utility methodologies used for determining extrapolated as way to rank-order based their relative properties. devised two approaches accomplish this: 1) vapor diffusion technique utilized traditional protein...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLocal and Global Dynamics during the Folding of Escherichia coli Dihydrofolate Reductase by Time-Resolved Fluorescence SpectroscopyBryan E. Jones, Joseph M. Beechem, C. Robert MatthewsCite this: Biochemistry 1995, 34, 6, 1867–1877Publication Date (Print):February 14, 1995Publication History Published online1 May 2002Published inissue 14 February 1995https://pubs.acs.org/doi/10.1021/bi00006a007https://doi.org/10.1021/bi00006a007research-articleACS...
Human activated protein C (APC) is an antithrombotic, antiinflammatory serine protease that plays a central role in vascular homeostasis, and recombinant C, drotrecogin alfa (activated), has been shown to reduce mortality patients with severe sepsis. Similar other proteases, functional APC levels are regulated by the inhibitor family of proteins including α 1 -antitrypsin inhibitor. Using APC–substrate modeling, we designed produced number derivatives goal altering proteolytic specificity...
Amino acid sequences in proteins can contain residues which complicate biochemical, biophysical, or protein engineering studies but are not essential for folding activity. Their replacement with other naturally-occurring amino acids subject to such complications maintain properties of the is a desirable goal. A simple strategy testing various mutants their suitability described pair cysteine dihydrofolate reductase (DHFR) from Escherichia coli. Using reconstructed gene preserves sequence and...
Skeletal muscle wasting occurs in a great majority of cancer patients with advanced disease and is associated poor prognosis decreased survival. Myostatin functions as negative regulator skeletal mass has recently become therapeutic target for reducing the loss strength clinical myopathies. We generated neutralizing antibodies to myostatin test their potential use agents attenuate due cancer. show that our antimyostatin significantly increase body weight, mass, non-tumor-bearing mice...
The crucial step in drug discovery is the identification of a lead compound from vast chemical library by any number screening techniques. NMR-based has advantage directly detecting binding to target. spectra resulting these screens can also be very complex and difficult analyze, making this an inefficient process. We present here method, RAMPED-UP NMR, (Rapid Analysis Multiplexing Experimentally Discriminated Uniquely Labeled Proteins using NMR) which generates simple are easy interpret...
Human follistatin is a regulatory glycoprotein with widespread biologic functions, including antiinflammatory activities, wound-healing properties, and muscle-stimulating effects. The role of in wide range activities shows promise for potential clinical application, which has prompted considerable interest the investigation protein as disease-modifying agent. In spite this potential, development broad use biotherapeutic been severely hindered by poor understanding characterization its...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDevelopment of Nonpolar Surfaces in the Folding Escherichia coli Dihydrofolate Reductase Detected by 1-Anilinonaphthalene-8-sulfonate BindingBryan E. Jones, Patricia A. Jennings, Richard Pierre, and C. Robert MatthewsCite this: Biochemistry 1994, 33, 51, 15250–15258Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December...
Abstract The histidine‐containing protein (HPr) of bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) serves a central role in series phosphotransfer reactions used for the translocation sugars across cell membranes. These studies report high‐definition solution structures both unphosphorylated and histidine phosphorylated (P‐His) forms HPr from Bacillus subtilis. Consistent with previous NMR studies, local conformational adjustments occur upon phosphorylation His 15, which...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCollapse of parallel folding channels in dihydrofolate reductase from Escherichia coli by site-directed mutagenesisMasahiro Iwakura, Bryan E. Jones, Christopher J. Falzone, and C. Robert MatthewsCite this: Biochemistry 1993, 32, 49, 13566–13574Publication Date (Print):December 14, 1993Publication History Published online1 May 2002Published inissue 14 December...
Advances in antibody discovery technologies, especially with the availability of humanized mice and phage/yeast library approaches, enable generation a large diversity antibodies against nearly any target interest. As result, there is an increasing demand for production larger numbers purified at quantities (10s-100s milligrams) sufficient functional screening assays, drug-ability/develop-ability studies immunogenicity assessments. To accommodate this need, new methods are required that...
<p>Supplementary Figure 6. LY2495655 attenuates the loss of muscle weight normalized to brain in PC3 tumor model.</p>
<p>Supplementary Figure 4. LY2495655 attenuates loss of muscle weight normalized to brain but has no effect on or heart in C26 tumor bearing mice the presence gemcitabine.</p>