A5018701434- Prostate Cancer Treatment and Research
- Radiopharmaceutical Chemistry and Applications
- Cancer Cells and Metastasis
- Cancer, Lipids, and Metabolism
- Cancer Treatment and Pharmacology
- Cellular Mechanics and Interactions
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Galectins and Cancer Biology
- Mesenchymal stem cell research
- Cancer Research and Treatments
- 3D Printing in Biomedical Research
- Caveolin-1 and cellular processes
- Mass Spectrometry Techniques and Applications
- Tissue Engineering and Regenerative Medicine
- Renal and related cancers
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Genetic and Kidney Cyst Diseases
- Spaceflight effects on biology
- Erythrocyte Function and Pathophysiology
- Gut microbiota and health
- Barrier Structure and Function Studies
- Hair Growth and Disorders
- Biomedical Research and Pathophysiology
Johns Hopkins University
2016-2025
Auburn University
2020-2024
Johns Hopkins Medicine
2019-2021
University at Buffalo, State University of New York
2011-2019
National Technical University of Athens
2007-2008
Abstract Cells respond to physical stimuli, such as stiffness 1 , fluid shear stress 2 and hydraulic pressure 3,4 . Extracellular viscosity is a key cue that varies under physiological pathological conditions, cancer 5 However, its influence on biology the mechanism by which cells sense changes in are unknown. Here we demonstrate elevated counterintuitively increases motility of various cell types two-dimensional surfaces confinement, dissemination from three-dimensional tumour spheroids....
The existence of distinct breast microbiota has been recently established, but their biological impact in cancer remains elusive. Focusing on the shift microbial community composition diseased compared with normal breast, we identified presence Bacteroides fragilis cancerous breast. Mammary gland as well gut colonization enterotoxigenic (ETBF), which secretes B. toxin (BFT), rapidly induces epithelial hyperplasia mammary gland. Breast cells exposed to BFT exhibit "BFT memory" from initial...
The breast cancer tumor microenvironment (TME) is dynamic, with various immune and non-immune cells interacting to regulate progression anti-tumor immunity. It now evident that the within TME significantly contribute resistance conventional newly developed therapies. Both in play critical roles onset, uncontrolled proliferation, metastasis, evasion, Consequently, molecular cellular components of have emerged as promising therapeutic targets for developing novel treatments. primarily...
Cells migrate in vivo through complex confining microenvironments, which induce significant nuclear deformation that may lead to blebbing and envelope rupture. While actomyosin contractility has been implicated regulating integrity, the exact mechanism remains unknown. Here, we argue confinement-induced activation of RhoA/myosin-II contractility, coupled with LINC complex-dependent anchoring at cell posterior, locally increases cytoplasmic pressure promotes passive influx constituents into...
Tumor cell intravasation preferentially occurs in regions of low fluid shear because high is detrimental to tumor cells. Here, we describe a molecular mechanism by which cells avoid during intravasation. The transition from migration was modeled using microfluidic device where migrating inside longitudinal tissue-like microchannels encounter an orthogonal channel flow induces physiological stresses. This approach complemented with intravital microscopy, patch-clamp, and signal transduction...
Abstract Cell migration regulates diverse (patho)physiological processes, including cancer metastasis. According to the Osmotic Engine Model, polarization of NHE1 at leading edge confined cells facilitates water uptake, cell protrusion and motility. The physiological relevance Model identity molecules mediating rear shrinkage remain elusive. Here, we demonstrate that SWELL1 preferentially polarize trailing edges, respectively, mediate volume regulation, dissemination from spheroids...
Abstract The role of mechanical forces driving kidney epithelial fluid transport and morphogenesis in diseases is unclear. Here, using a microfluidic platform to recapitulate activity cells, we report that renal cells can actively generate hydraulic pressure gradients across the epithelium. fluidic flux declines with increasing until stall pressure, manner similar pumps. For normal human from apical basal, higher on basal side. Autosomal Dominant Polycystic Kidney Disease reversed apical....
Although the therapeutic potential of mesenchymal stem cells (MSCs) is widely accepted, loss cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSCs originating from older donors suffer limited proliferative capacity and significantly reduced myogenic differentiation potential. This a concern, as patients most likely cardiovascular disease elderly. Here we tested hypothesis single...
Smooth muscle cells (SMC) play an important role in vascular homeostasis and disease. Although adult mesenchymal stem (MSC) have been used as a source of contractile SMC, they suffer from limited proliferation potential culture senescence, particularly when originating older donors. By comparison, human induced pluripotent (hiPSC) can provide unlimited functional SMC for autologous cell-based therapies creating models Our goal was to develop efficient strategy derive functional, hiPSC. We...
The adult body harbors powerful reservoirs of stem cells that enable tissue regeneration under homeostatic conditions or in response to disease injury. hair follicle (HF) is a readily accessible mini organ within the skin and contains from diverse developmental origins were shown have surprisingly broad differentiation potential. In this review, we discuss biology HF with particular emphasis on various cell populations residing tissue. We summarize existing knowledge putative markers,...
TRPM7 senses hydraulic pressure and modulates cortical actomyosin to guide migrating cells towards the path of lower resistance.
How migrating cells differentially adapt and respond to extracellular track geometries remains unknown. Using intravital imaging, we demonstrate that invading exhibit dorsoventral (top-to-bottom) polarity in vivo. To investigate the impact of on cell locomotion through different confining geometries, fabricated microchannels fixed cross-sectional area, albeit with distinct aspect ratios. Vertical confinement, exerted along axis, induces myosin II-dependent nuclear stiffening, which results...
Cells migrate in vivo through channel-like tracks. While polydimethylsiloxane devices emulate such tracks vitro, their channel walls are impermeable and have supraphysiological stiffness. Existing hydrogel-based platforms address these issues but cannot provide high-throughput analysis of cell motility independently controllable stiffness confinement. We herein develop polyacrylamide (PA)-based microchannels physiological prescribed dimensions for migration identify a biphasic dependence...
Cells tune adherens junction dynamics to regulate epithelial integrity in diverse (patho)physiological processes, including cancer metastasis. We hypothesized that the spatially confining architecture of peritumor stroma promotes metastatic cell dissemination by remodeling cell-cell adhesive interactions. By combining microfluidics with live-cell imaging, FLIM/FRET biosensors, and optogenetic tools, we show confinement induces leader dissociation from cohesive ensembles. Cell is triggered...
Abstract The sialoglycoprotein podocalyxin is absent in normal pancreas but overexpressed pancreatic cancer and associated with poor clinical outcome. Here, we investigate the role of migration metastasis adenocarcinomas using SW1990 Pa03c as cell models. Although ezrin regarded a cytoplasmic binding partner that regulates actin polymerization via Rac1 or RhoA, did not detect podocalyxin–ezrin association cells. Moreover, depletion alter dynamics modulate RhoA activities Using mass...
Cellular senescence as a result of organismal aging or progeroid diseases leads to stem cell pool exhaustion hindering tissue regeneration and contributing the progression age related disorders. Here we discovered that ectopic expression pluripotent factor NANOG in senescent myogenic progenitors reversed cellular restored completely ability generate contractile force. To elicit its effects, enabled reactivation ROCK Transforming Growth Factor (TGF)-β pathways-both which were impaired...