A5001306209- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Microtubule and mitosis dynamics
- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Cystic Fibrosis Research Advances
- Force Microscopy Techniques and Applications
- Nanoparticle-Based Drug Delivery
- Immunodeficiency and Autoimmune Disorders
- Cell Image Analysis Techniques
- Heat shock proteins research
- Cancer Research and Treatments
- Cardiomyopathy and Myosin Studies
- Caveolin-1 and cellular processes
- Tendon Structure and Treatment
- Neonatal Respiratory Health Research
- Muscle Physiology and Disorders
- Bone Tissue Engineering Materials
- Click Chemistry and Applications
- Cancer Cells and Metastasis
- Advanced biosensing and bioanalysis techniques
- Nuclear Structure and Function
- Asthma and respiratory diseases
- Advanced Fluorescence Microscopy Techniques
- Silk-based biomaterials and applications
Johns Hopkins University
2013-2020
Johns Hopkins Medicine
2013-2020
University of Baltimore
2014-2018
Metastasis is complex, involving multiple genetic, epigenetic, biochemical, and physical changes in the cancer cell its microenvironment. Cells with metastatic potential are often characterized by altered cellular contractility deformability, lending them flexibility to disseminate navigate through different microenvironments. We demonstrate that mechanoresponsiveness a hallmark of pancreatic cells. Key mechanoresponsive proteins, those accumulate response mechanical stress, specifically...
Metastases are the cause of vast majority cancer deaths. In metastatic process, cells migrate to vasculature, intravasate, extravasate, and establish colonies. This pattern spread requires change shape navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show 4-hydroxyacetophenone (4-HAP) inhibits colon cell adhesion, invasion, migration in vitro reduces burden an vivo model metastasis liver. Treatment with 4-HAP activates nonmuscle...
Dynamical cell shape changes require a highly sensitive cellular system that can respond to chemical and mechanical inputs. Myosin IIs are key players in the cell’s ability react inputs, demonstrating an accumulate response applied stress. Here, we show inputs influence of myosin II assemble into filaments impact stress predictable manner. Using mathematical modeling for Dictyostelium II, predict mechanoresponsiveness will be biphasic with optimum established by percentage assembled bipolar...
Multiple sodium and chloride channels on the apical surface of nasal epithelial cells contribute to periciliary fluid homeostasis, a function that is disrupted in patients with cystic fibrosis (CF). Among these channel CLCN2, which has been studied as potential alternative efflux pathway absence CFTR. The object present study was use difference test (NPD) quantify CLCN2 an epithelial-directed TetOn transgenic mouse model (TGN-K18rtTA-hCLCN2) by using putative pharmacological agonist...
It is recognized that both wild-type and mutant CFTR proteins undergo ubiquitination at multiple lysines in the one or more subcellular locations. We hypothesized ubiquitin added to specific sites stabilize it other signal for proteolysis. Mass spectrometric analysis of identified ubiquitinated 68, 710, 716, 1041, 1080. demonstrate K710, K716, K1041 residues CFTR, protecting from The polyubiquitin linkage predominantly K63. N-tail mutants, K14R K68R, lead increased mature band CCFTR, which...
Cellular mechanosensing is critical for many biological processes, including cell differentiation, proliferation, migration, and tissue morphogenesis. The actin cytoskeletal proteins play important roles in cellular mechanosensing. Many techniques have been used to investigate the mechanosensory behaviors of these proteins. However, a fast, low-cost assay quantitative characterization still lacking. Here, we demonstrate that compression using agarose overlay suitable high throughput...
Abstract Metastatic disease is often characterized by altered cellular contractility and deformability, lending cells groups of the flexibility to navigate through different microenvironments. This ability change cell shape driven in large part structural elements mechanobiome, which includes cytoskeletal proteins that sense respond mechanical stimuli. Here, we demonstrate key mechanoresponsive (those accumulate response stress), specifically nonmuscle myosin IIA IIC, α-actinin 4, filamin B,...
Cystic Fibrosis (CF) is an autosomal recessive disease, characterized by mutations in the CFTR gene, incorrect protein folding, and impaired chloride secretion. In addition to maintenance of secretion, also suggested be important regulator epithelial sodium channel (ENaC) activity. We previously identified ClCN2 as coexpressed with mutant hypothesized that restoring can act a negative ENaC. Coimmunoprecipitation analysis shows novel physical interaction between ENaC pulmonary epithelium,...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality, with 37,000 people dying annually in the US. Existing strategies for treating primarily mainly focus on inhibiting cell growth through specific genetic pathways, which typically either fail to completely abolish disease or lead compensatory regulatory changes, and hence, drug resistance. Targeting mechanics remains an under-used approach development. The direct driver shape change events intrinsic...
<p>Supplemental materials include following: Supplemental Materials and Methods Table S1. NMII Concentration (n), nM Fig. Model systems to human pancreatic cancer. S2. Scoring analysis differential expression patterns of mechanoresponsive non-mechanoresponsive paralogs in patient-derived IHC data. S3: Measurement endogenous nonmuscle myosin II the effect knockdown, overexpression, 4-HAP treatment on mechanobiome proteins. S4. Pancreatic cancer cell lines are mechanically distinct from...
<div>Abstract<p>Metastasis is complex, involving multiple genetic, epigenetic, biochemical, and physical changes in the cancer cell its microenvironment. Cells with metastatic potential are often characterized by altered cellular contractility deformability, lending them flexibility to disseminate navigate through different microenvironments. We demonstrate that mechanoresponsiveness a hallmark of pancreatic cells. Key mechanoresponsive proteins, those accumulate response...
<p>Supplemental materials include following: Supplemental Materials and Methods Table S1. NMII Concentration (n), nM Fig. Model systems to human pancreatic cancer. S2. Scoring analysis differential expression patterns of mechanoresponsive non-mechanoresponsive paralogs in patient-derived IHC data. S3: Measurement endogenous nonmuscle myosin II the effect knockdown, overexpression, 4-HAP treatment on mechanobiome proteins. S4. Pancreatic cancer cell lines are mechanically distinct from...
<div>Abstract<p>Metastasis is complex, involving multiple genetic, epigenetic, biochemical, and physical changes in the cancer cell its microenvironment. Cells with metastatic potential are often characterized by altered cellular contractility deformability, lending them flexibility to disseminate navigate through different microenvironments. We demonstrate that mechanoresponsiveness a hallmark of pancreatic cells. Key mechanoresponsive proteins, those accumulate response...
Rationale Post‐translational modification of lysine residues in CFTR is predicted to regulate trafficking and recycling. We hypothesized that disruption ubiquitination will accelerate destruction wt increase inflammatory responses. Methods Site‐directed mutagenesis, Immunoblot, confocal analysis, ELISA assay, etc. Results identify seven key lysines protein expression, maturation, poly‐ubiquitination, subsequently, its role More specifically, K14/K68/K1218 are important for lysosomal...