A5085809373- Monoclonal and Polyclonal Antibodies Research
- Blood properties and coagulation
- Skin and Cellular Biology Research
- Erythrocyte Function and Pathophysiology
- CAR-T cell therapy research
- Protein purification and stability
- Biosimilars and Bioanalytical Methods
- HER2/EGFR in Cancer Research
- Proteins in Food Systems
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Viral Infectious Diseases and Gene Expression in Insects
- T-cell and B-cell Immunology
- Rheumatoid Arthritis Research and Therapies
- Peptidase Inhibition and Analysis
- Fibroblast Growth Factor Research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Proteoglycans and glycosaminoglycans research
- Biomedical and Engineering Education
- Hair Growth and Disorders
- Dermatologic Treatments and Research
- Galectins and Cancer Biology
- Phagocytosis and Immune Regulation
AbbVie (United States)
2015-2024
Massachusetts Academy of Math and Science
2012-2015
Sanofi (France)
2015
Bristol-Myers Squibb (United States)
2015
Eli Lilly (United States)
2015
Biogen (United States)
2015
Amgen (United States)
2015
Novartis (Switzerland)
2015
Pfizer (United States)
2015
GlaxoSmithKline (United Kingdom)
2015
Peptidylarginine deiminases, which are commonly found in mammalian cells, catalyze the deimination of protein-bound arginine residues to citrullines. However, very little is known about their substrate requirements and significance or consequences this postsynthetic modification. We have explored reaction vitro with two substrates filaggrin trichohyalin. First, degree rate modification arginines citrullines directly correlates structural order substrate. In filaggrin, has order, proceeded...
Physiological deletion of cells ensues programmed death which involves formation apoptotic bodies with fragmented DNA. Here we report that hepatocytes are insoluble in detergents, urea, guanidine hydrochloride, reducing agents and thereby can be isolated from rat liver following collagenase treatment. They wrinkled, spherical structures similar to cornified envelopes epidermis by phase‐contrast microscopy show irregular, globular morphology scanning‐electron microscopy. Part their DNA...
Trichohyalin (THH) is a major structural protein of the inner root sheath cells and medulla layer hair follicle and, to lesser extent, other specialized epithelia. THH high molecular weight insoluble α-helix-rich that forms rigid structures as result postsynthetic modifications by two Ca2+-dependent enzymes, transglutaminases (TGases) (protein cross-linking) peptidyl-arginine deiminase (conversion arginines citrullines with loss organized structure). The modified thought serve keratin...
Recombinant adeno-associated virus (AAV) vectors are the leading delivery vehicle used for
We have addressed the question of how keratin intermediate filaments are associated with cell envelope at periphery cornified epidermal cells. Many peptides from human envelopes containing isopeptide crosslinks inserted by transglutaminases in vivo been characterized. A major subset involves type II chains 1, 2e, 5, or 6 crosslinked to several protein partners through a lysine residue located conserved region V1 subdomain their head domains. This sequence specificity was confirmed vitro...
The ubiquitin-proteasome pathway is believed to selectively degrade post-synthetically damaged proteins in eukaryotic cells. To study this process we used calmodulin (CaM) as a substrate because of its importance cell regulation and it acquires isoaspartyl residues Ca<sup>2+</sup>-binding regions both<i>in vivo</i> after <i>in vitro</i> "aging" (incubation for 2 weeks without Ca<sup>2+</sup>). When microinjected into <i>Xenopus</i> oocytes, aged CaM was degraded much faster than native by...
Small proline-rich 1 (SPR1) proteins are important for barrier function in stratified squamous epithelia. To explore their properties, we expressed bacteria a recombinant human SPR1 protein and isolated native from cultured mouse keratinocytes. By circular dichroism, they possess no α or β structure but have some organized associated with central peptide repeat domain. The transglutaminase (TGase) 3 enzymes use the as complete substrates vitro different ways: head domain A sequences at amino...
Abstract The Bcl-2 family of proteins plays a critical role in controlling immune responses by regulating the expansion and contraction activated lymphocyte clones apoptosis. ABT-737, which was originally developed for oncology, is potent inhibitor Bcl-2, Bcl-xL, Bcl-w protein function. There evidence that Bcl-2–associated dysregulation apoptosis may contribute to pathogenesis autoimmunity lead development autoimmune diseases. In this study, we report ABT-737 treatment resulted inhibition...
Interleukin-1 (IL-1) cytokines such as IL-1α, IL-1β, and IL-1Ra contribute to immune regulation inflammatory processes by exerting a wide range of cellular responses, including expression chemokines, matrix metalloproteinases, nitric oxide synthetase. IL-1α IL-1β bind IL-1R1 complexed the IL-1 receptor accessory protein induce similar physiological effects. Preclinical clinical studies provide significant evidence for role in pathogenesis osteoarthritis (OA), cartilage degradation, bone...
The rapid and direct analysis of the amount spatial distribution exogenous chloroquine (CHQ) CHQ metabolites from tissue sections by liquid extraction surface sampling coupled with tandem mass spectrometry (LESA‐MS/MS) was demonstrated. LESA‐MS/MS results compared well previously published quantification data collected organ excision, fluorescent detection. ability to directly sample analyze spatially resolved molecules minimal preparation analytical method development has potential...
The small proline-rich (SPR) proteins are components of the cornified cell envelope stratified squamous epithelia and become cross-linked to other by transglutaminases (TGases). SPR2 family is most complex, as it consists several differentially expressed members same size. To explore their physical cross-linking properties, we have in bacteria a human member, purified homogeneity. By circular dichroism, possesses no α or β structure but has some organized associated with central peptide...
ε(γ‐Glutamyl)lysine isodipeptide, the end‐product of proteolytic digestion proteins cross‐linked by transglutaminase, was detected in culture fluid neonatal rat hepatocytes and plasma adult rats. The concentration isodipeptide significantly increased both when high rate apoptosis with phagocytosis dying produced either epidermal growth factor or lead nitrate‐induced hyperplasia subsequent involution Specific induction tissue transglutaminase consequent formation highly protein envelopes...
ABT-736 is a humanized monoclonal antibody generated to target specific conformation of the amyloid-beta (Aβ) protein oligomer. Development for Alzheimer’s disease was discontinued due severe adverse effects (AEs) observed in cynomolgus monkey toxicity studies. The acute nature AEs only at highest doses suggested potential binding an abundant plasma protein. Follow-up investigations indicated polyspecificity ABT-736, including unintended high-affinity and human platelet factor 4 (PF-4),...