A5082486274- Cellular Mechanics and Interactions
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Microtubule and mitosis dynamics
- T-cell and B-cell Immunology
- Signaling Pathways in Disease
- Nuclear Structure and Function
- Malaria Research and Control
- Silk-based biomaterials and applications
- Blood properties and coagulation
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Genetic Neurodegenerative Diseases
- TGF-β signaling in diseases
- Erythrocyte Function and Pathophysiology
- RNA Research and Splicing
- Cellular transport and secretion
- PI3K/AKT/mTOR signaling in cancer
- Asthma and respiratory diseases
- Phenothiazines and Benzothiazines Synthesis and Activities
- Marine Biology and Environmental Chemistry
- Polyamine Metabolism and Applications
- NF-κB Signaling Pathways
Loyola University Chicago
2019-2025
Case Western Reserve University
2009-2023
Cleveland Clinic
2010-2023
Union University
2023
University of Chicago
2022
Cleveland Clinic Lerner College of Medicine
2009-2017
National Institutes of Health
2014-2017
National Heart Lung and Blood Institute
2015-2017
University School
2009
University of Oklahoma
2009
Adding to the super-resolution arsenal Structured illumination microscopy (SIM) uses light intensities that are orders of magnitude lower than other methods. SIM is also far faster over cellular-sized fields view. Li et al. used two approaches improve resolution allow live cell imaging dynamic cellular processes, including endocytosis and cytoskeleton remodeling. The contrast in performance between techniques due a few key differences. Defining practical at limited signal-to-noise ratios...
Actin assembly and inward flow in the plane of immunological synapse (IS) drives centralization T cell receptor microclusters (TCR MCs) integrin leukocyte functional antigen 1 (LFA-1). Using structured-illumination microscopy (SIM), we show that actin arcs populating medial, lamella-like region IS arise from linear filaments generated by one or more formins present at distal edge. After traversing outer, Arp2/3-generated, lamellipodia-like IS, these are organized myosin II into antiparallel...
Non-muscle myosin II (NMII) is reported to play multiple roles during cell migration and invasion. However, the exact biophysical of different NMII isoforms these processes remain poorly understood. We analyzed contributions NMIIA NMIIB in three-dimensional (3D) generating forces required for efficient invasion by mammary gland carcinoma cells. Using traction force microscopy microfluidic devices, we demonstrated that critical active protrusion, plays a major role applying on nucleus...
The ability to dynamically assemble contractile networks is required throughout cell physiology, yet direct biophysical mechanisms regulating non-muscle myosin 2 filament assembly in living cells are lacking. Here, we use a suite of dynamic, quantitative imaging approaches identify deterministic factors that drive appearance and amplification. We find actin dynamics regulate assembly, but the static architecture plays less clear role. Instead, remodeling modulates local monomer levels...
Despite functional significance of nonmuscle myosin II in cell migration and invasion, its role epithelial–mesenchymal transition (EMT) or TGF-β signaling is unknown. Analysis normal mammary gland expression revealed that IIC expressed luminal cells, whereas IIB up-regulated myoepithelial cells have more mesenchymal characteristics. Furthermore, induction EMT nontransformed murine epithelial results an isoform switch from to increased phosphorylation heavy chain (MHC) IIA on target sites...
Hepatocellular carcinoma (HCC) remains one of the deadliest malignancies worldwide. One major obstacle to treatment is a lack effective molecular-targeted therapies. In this study, we find that EphA2 expression and signaling are enriched in human HCC associated with poor prognosis. Loss suppresses initiation growth both vitro vivo. Furthermore, CRISPR/CAS9-mediated inhibition significantly delays tumor development genetically engineered murine model HCC. Mechanistically, discover targeting...
Phosphorylation of non-muscle myosin II regulatory light chain (RLC) at Thr18/Ser19 is well established as a key event that controls assembly and activation, both in vitro living cells. RLC can also be phosphorylated Ser1/Ser2/Thr9 by protein kinase C (PKC). Biophysical studies show phosphorylation these sites leads to an increase the Km (MLCK) for RLC, thereby indirectly inhibiting activity. Despite unequivocal evidence PKC regulate function vitro, there little this mechanism regulates live...
Abstract Platinum compounds remain the backbone of chemotherapy regimens for a variety solid tumors, despite their well-described adverse effects nephrotoxicity, ototoxicity, and neurotoxicity. Cisplatin ototoxicity results from damage to cochlear outer hair cells remains key dose-limiting toxicity in pediatric cancers, where its incidence reaches as high 90% testicular cancer patients. However, mechanistic underpinnings cisplatin incompletely understood no treatments exist prevent onset....
As microtubule-organizing centers, centrosomes direct assembly of the bipolar mitotic spindle required for chromosome segregation and genome stability. Centrosome activity requires dynamic pericentriolar material (PCM), composition organization which changes throughout cell cycle. Recent studies highlight conserved localization several mRNAs encoded from centrosome-associated genes enriched at centrosomes, including Pericentrin-like protein ( Plp) mRNA. However, relatively little is known...
Bladder cancer is the fourth most common cause of in males United States. Invasive behavior a major determinant prognosis. In this study, we identified mammalian target rapamycin complex 2 (mTORC2) as central regulator bladder cell migration and invasion. mTORC2 activity was assessed by extent phosphorylation Ser473 AKT determined to be approximately 5-fold higher specimens invasive human opposed non-invasive cancer. The immortalized malignant lines, UMUC-3, J82 T24 demonstrated baseline...
The ATP-dependent ion pump sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ in the endoplasmic to establish a reservoir for cell signaling. Because of its central importance physiology, activity this transporter is tightly controlled via direct interactions with tissue-specific regulatory micropeptides that tune SERCA function match changing physiological conditions. In heart, micropeptide phospholamban (PLB) inhibits SERCA, while dwarf open reading frame (DWORF) stimulates...
The peri-centrosomal localization and morphology of the Golgi apparatus depends largely on microtubule cytoskeleton motor protein dynein. Recent studies proposed that myosin 18Aα (M18Aα) also contributes to by binding GOLPH3 walking along adjacent actin filaments stretch into its classic ribbon structure. Biochemical analyses have shown, however, M18A is not an actin-activated ATPase lacks activity. Our goal, therefore, was define precise molecular mechanism which M18Aα determines...
Malaria elimination urgently needs novel antimalarial therapies that transcend resistance, toxicity, and high costs. Our multicentric international collaborative team focuses on developing multistage antimalarials exhibit mechanisms of action. Here, we describe the design, synthesis, evaluation a compound, 'Calxinin'. A compound consists hydroxyethylamine (HEA) trifluoromethyl-benzyl-piperazine. Calxinin exhibits potent inhibitory activity in nanomolar range against asexual blood stages...
SUMMARY Allergen-specific IgE is a key mediator of allergic asthma. However, the tissue sites and cell types that support production at mucosa remained undefined. Here, we reveal inhaled allergens induce formation IgG1 + lung-resident memory B cells (MBC) switch to IgE. Using mouse reporter for class recombination, requirement generation IgE, identify lung tissues as major site switching, which dominated by MBCs supported IL-4-producing T H 2 cells. This in sharp contrast what occurs...