A5004776840- 3D Printing in Biomedical Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Inhalation and Respiratory Drug Delivery
- Monoclonal and Polyclonal Antibodies Research
- Pluripotent Stem Cells Research
- CAR-T cell therapy research
- Cell Image Analysis Techniques
- Cancer Cells and Metastasis
- Bacterial Infections and Vaccines
- Nanofabrication and Lithography Techniques
- Cellular transport and secretion
- Bone and Joint Diseases
- Microfluidic and Bio-sensing Technologies
- Platelet Disorders and Treatments
- Intravenous Infusion Technology and Safety
- Liver physiology and pathology
- Tissue Engineering and Regenerative Medicine
- Hemoglobinopathies and Related Disorders
- Acute Ischemic Stroke Management
- Planarian Biology and Electrostimulation
- Photoacoustic and Ultrasonic Imaging
- Synthesis of Indole Derivatives
- Barrier Structure and Function Studies
- Single-cell and spatial transcriptomics
- Gastrointestinal motility and disorders
University of Cincinnati
2020-2024
Cincinnati Children's Hospital Medical Center
2021-2024
Emulate (United States)
2018-2023
Cedars-Sinai Medical Center
2017-2019
BioMimetic Systems (United States)
2016
Riverbank Local Redevelopment Authority
2016
Harvard University
2016
Novartis (Switzerland)
2011-2015
Novartis (Italy)
2013-2014
Toscana Life Sciences
2013
A rat, dog, and human Liver-Chip designed using microengineered Organs-on-Chips technology recapitulates species-specific drug toxicities.
Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models thrombi formation human lung microvessels that could also assess therapeutics and toxicology antithrombotic drugs. Here, we show microfluidic alveolus‐on‐a‐chip lined by primary alveolar epithelium interfaced with endothelium cultured under flowing whole blood can be used to perform quantitative analysis organ‐level contributions inflammation‐induced thrombosis. This chip...
The vascular endothelium and shear stress are critical determinants of physiological hemostasis platelet function in vivo, yet current diagnostic monitoring devices do not fully incorporate endothelial under flow their assessment and, therefore, they can be unreliable inaccurate. It is challenging to include the assays for clinical laboratories or point-of-care settings because living cell cultures sufficiently robust. Here, we describe a microfluidic device that lined by human chemically...
We establish a murine lung-on-chip infection model and use time-lapse imaging to reveal the dynamics of host- Mycobacterium tuberculosis interactions at an air-liquid interface with spatiotemporal resolution unattainable in animal models probe direct role pulmonary surfactant early infection. Surfactant deficiency results rapid uncontrolled bacterial growth both macrophages alveolar epithelial cells. In contrast, under normal levels, significant fraction intracellular bacteria are...
Clinical development of Hu5c8, a monoclonal antibody against CD40L intended for treatment autoimmune disorders, was terminated due to unexpected thrombotic complications. These life‐threatening side effects were not discovered during preclinical testing the lack predictive models. In present study, we describe microengineered system lined by human endothelium perfused with whole blood, “Vessel‐Chip.” The Vessel‐Chip allowed us evaluate key parameters in thrombosis, such as endothelial...
Abstract Understanding the complexities of human brain’s function in health and disease is a formidable challenge neuroscience. While traditional models like animals offer valuable insights, they often fall short accurately mirroring biology drug responses. Moreover, recent legislation has underscored need for more predictive that represent physiology. To address this requirement, human-derived cell cultures have emerged as crucial alternative biomedical research. However, static culture...
Traditional drug safety assessment often fails to predict complications in humans, especially when the targets immune system. Here, we show unprecedented capability of two human Organs-on-Chips evaluate profile T-cell bispecific antibodies (TCBs) targeting tumor antigens. Although promising for cancer immunotherapy, TCBs are associated with an on-target, off-tumor risk due low levels expression antigens healthy tissues. We leveraged vivo target and toxicity data folate receptor 1 (FOLR1) or...
The contribution of Clostridium difficile toxin A and B (TcdA TcdB) to cellular intoxication has been studied extensively, but their impact on bacterial colonization remains unclear. By setting up 2- 3-dimensional in vitro models polarized gut epithelium, we investigated how C. infection is affected by host cell polarity whether TcdA TcdB contribute such events. Indeed, observed that adhesion penetration the mucosal barrier are substantially enhanced poorly or ethylene glycol tetraacetic...
NadA (N eisseria meningitidisadhesin A), a meningococcal surface protein, mediates adhesion to and invasion of human cells, an activity in which host membrane proteins have been implicated. While investigating these factors epithelial cells by affinity chromatography, we discovered unanticipated interaction with heat shock protein (Hsp) 90, molecular chaperone. The specific vitro recombinant soluble Hsp90 was confirmed co-immunoprecipitations, dot far-Western blot. Intriguingly, ADP, but not...
Translocation of the nasopharyngeal barrier by Neisseria meningitidis occurs via an intracellular microtubule-dependent pathway and represents a crucial step in its pathogenesis. Despite this fact, interaction invasive meningococci with host subcellular compartments resulting impact on their organization function have not been investigated. The influence serogroup B strain MC58 cell polarity trafficking system was assessed confocal microscopy visualization different plasma...
Abstract Microphysiological systems (MPSs) reconstitute tissue interfaces and organ functions, presenting a promising alternative to animal models in drug development. However, traditional materials like polydimethylsiloxane (PDMS) often interfere by absorbing hydrophobic molecules, affecting testing accuracy. Additive manufacturing, including 3D bioprinting, offers viable solutions. GlioFlow3D, novel microfluidic platform combining extrusion bioprinting stereolithography (SLA) is...
In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability clonogenicity both primary brain-metastatic NSCLC cells. Employing human-relevant ex vivo ‘chip’, AM-101 is as efficacious docetaxel, chemotherapeutic used with for advanced-stage NSCLC. vivo, potentiates radiation, including conferring significant survival benefit to mice...
Neisseria meningitidis is a human pathogen that can cause fatal sepsis and meningitis once it reaches the blood stream nervous system. Here we demonstrate fragment, released upon proteolysis of surface-exposed protein Neisserial Heparin Binding Antigen (NHBA), by bacterial protease NalP, alters endothelial permeability inducing internalization adherens junction VE-cadherin. We found C2 rapidly accumulates in mitochondria where induces production reactive oxygen species: latter are required...
Neisseria meningitidis adhesin A (NadA) is a meningococcus surface protein thought to assist in the adhesion of bacterium host cells. We have previously shown that NadA also promotes bacterial internalization heterologous expression system. Here we used soluble recombinant (rNadA) lacking membrane anchor region characterize its route Chang epithelial Added culture medium, rNadA internalizes through PI3K-dependent endocytosis process not mediated by canonical clathrin or caveolin scaffolds,...
Traditional drug safety assessments often fail to predict complications in humans, especially when the targets immune system. Rodent-based preclinical animal models are ill-suited for predicting immunotherapy-mediated adverse events part because of fundamental differences immunological responses between species and human relevant expression profile target antigen, if it is expected be present normal, healthy tissue. While human-relevant cell-based tissues organs promise bridge this gap,...
The main objective of this study was to demonstrate that computational fluid dynamics (CFD) modeling can be used the contribution covert and overt vascular architecture risk for cerebrovascular disease in sickle cell (SCD) determine mechanisms response therapy such as chronic red blood (cRBC) transfusions. We analyzed baseline (screening), pre-randomization exit magnetic resonance angiogram (MRA) images from 10 (5 each transfusion observation arms) pediatric SCD participants silent cerebral...
Abstract Nonclinical rodent and non-rodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail predict complications in humans contributing drug failures the clinic. Here we applied microengineered Organ-on-Chip (Organ-Chip) technology design rat, dog, human Liver-Chips containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, without Kupffer cells hepatic stellate cultured under physiological...
Abstract Mycobacterium tuberculosis (Mtb) makes ‘first contact’ with a host in the alveolar space, an interaction largely inaccessible to experimental observation. We establish lung-on-chip model for early and use time-lapse imaging reveal dynamics of host-Mtb interactions at air-liquid interface spatiotemporal resolution unattainable animal models. By reconstituting physiology modular manner, we probe role pulmonary surfactant secreted by epithelial cells (AECs) infection. This is difficult...
Abstract In non-small cell lung cancer (NSCLC) treatment, targeted therapies help a subset of patients, and radiotherapy responses are not durable toxicity limits therapy. Most advanced-stage NSCLC patients have brain metastases that render an abysmal prognosis. Standard-of-care radiation therapy for metastasis includes stereotactic radiosurgery (SRS) if the number lesions is less than ten, otherwise whole (WBRT) administered. Challenges in applying include overcoming resistance reducing...