A5073214957- Barrier Structure and Function Studies
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Trace Elements in Health
- RNA and protein synthesis mechanisms
- Hemoglobinopathies and Related Disorders
- Immune cells in cancer
- Neurological Disease Mechanisms and Treatments
- Advanced biosensing and bioanalysis techniques
- Iron Metabolism and Disorders
- Obstructive Sleep Apnea Research
- Nasal Surgery and Airway Studies
- Orthopedic Surgery and Rehabilitation
- Olfactory and Sensory Function Studies
- Psychotherapy Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Neuroscience and Neural Engineering
- Neurogenesis and neuroplasticity mechanisms
- Cancer Cells and Metastasis
- Counseling, Therapy, and Family Dynamics
- Monoclonal and Polyclonal Antibodies Research
Vanderbilt University
2018-2025
Imperial College Healthcare NHS Trust
2014
St. Mary’s Hospital
2014
Human induced pluripotent stem cell (iPSC)-derived developmental lineages are key tools for in vitro mechanistic interrogations, drug discovery, and disease modeling. iPSCs have previously been differentiated to endothelial cells with blood-brain barrier (BBB) properties, as defined by high transendothelial electrical resistance (TEER), low passive permeability, active transporter functions. Typical protocols use undefined components, which impart unacceptable variability on the...
Abstract Astrocytes are critical components of the neurovascular unit that support blood-brain barrier (BBB) function. Pathological transformation astrocytes to reactive states can be protective or harmful BBB Here, using a human induced pluripotent stem cell (iPSC)-derived co-culture model, we show tumor necrosis factor (TNF) transitions an inflammatory state causes dysfunction through activation STAT3 and increased expression SERPINA3 , which encodes alpha 1-antichymotrypsin (α1ACT). To...
Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of iron homeostasis a significant factor in disorders. Understanding mechanism by which transport across blood–brain barrier (BBB) regulated crucial address impact deficiency on development excessive accumulation neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived endothelial cells (huECs) human BBB model, we...
There is a profound need for functional, biomimetic in vitro tissue constructs of the human blood-brain barrier and neurovascular unit (NVU) to model diseases identify therapeutic interventions. Here, we show that induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) exhibit robust functionality when cultured 3D channels within gelatin hydrogels. We determined BMECs under perfusion conditions were 10-100 times less permeable sodium fluorescein, 3 kDa...
Background: Functional rhinoplasty often relies on repurposed cartilage for nasal framework grafting. Objective: To compare complications in functional associated with use of autologous versus fresh frozen cadaveric rib (FFCR). Methods: This retrospective cohort study included patients who underwent from 2017 to 2022 6 months documented follow-up. The primary outcome measure was need revision rhinoplasty. Secondary outcomes were infection and persistent obstruction without surgery....
Whether iron formulations used therapeutically for a variety of conditions involving deficiency can deliver to the brain is significant clinical question given impact that loading has on in neurodegenerative diseases. In this study, we examine ability 5 pharmaceutical are intravenously treatment cross an vitro model blood-brain barrier. The uses human endothelial cells derived from induced pluripotent stem cells. We report that, compared natural delivery proteins, transferrin and H-ferritin,...
It is increasingly recognized that brain microvascular endothelial cells (BMECs), the principal component of blood-brain barrier (BBB), are highly sensitive to soluble cues from both bloodstream and brain. This concept extends in vitro, where extracellular milieu can also influence BBB properties cultured cells. However, extent which baseline culture conditions affect vitro remains unclear, has implications for model variability reproducibility, as well downstream assessments molecular...
Abstract Astrocytes are critical components of the neurovascular unit that support blood-brain barrier (BBB) function in brain microvascular endothelial cells (BMECs). Transformation astrocytes to a reactive state response injury and disease can be protective or harmful BBB function, but underlying mechanisms for these effects remain mostly unclear. Using human induced pluripotent stem cell (iPSC)-derived coculture model BMEC-like astrocytes, we found tumor necrosis factor alpha (TNFα)...
Abstract Glucose, a primary fuel source under homeostatic conditions, is transported into cells by membrane transporters such as glucose transporter 1 (GLUT1). Due to its essential role in maintaining energy homeostasis, dysregulation of GLUT1 expression and function can adversely affect many physiological processes the body. This has implications wide range disorders Alzheimer’s disease (AD) several types cancers. However, regulatory pathways that govern expression, which may be altered...
Abstract It is increasingly recognized that brain microvascular endothelial cells (BMECs), the principle component of blood-brain barrier (BBB), are highly sensitive to soluble cues from both bloodstream and brain. This concept extends in vitro , where extracellular milieu can also influence BBB properties cultured cells. However, extent which baseline culture conditions affect remains unclear, has implications for model variability reproducibility, as well downstream assessments molecular...
Abstract Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration immune across BBB is influenced by scaffold protein IQ motif containing GTPase activating 2 (IQGAP2). In mice and zebrafish,...
Standardized single cell seeding protocol for Blood-Brain Barrier (BBB) differentiation.
Human induced pluripotent stem cell (iPSC)-derived developmental lineages are key tools for invitro mechanistic interrogations, drug discovery, and disease modeling. iPSCs have previously been differentiated to endothelial cells with blood-brain barrier (BBB) properties, as defined by high transendothelial electrical resistance (TEER), low passive permeability, active transporter functions. Typical protocols use undefined components, which impart unacceptable variability on the...
Abstract Introduction The generation of affinity reagents that bind native membrane proteins with high specificity remains challenging. Most in vitro selection paradigms utilize different cell types for positive and negative rounds (where the is against a expresses desired protein lacks protein). However, this strategy can yield unintended on target cells. To address issue, we developed systematic evolution ligands by exponential enrichment (SELEX) scheme utilizes isogenic pairs cells...
Human induced pluripotent stem cell (iPSC)-derived developmental lineages are key tools for invitro mechanistic interrogations, drug discovery, and disease modeling. iPSCs have previously been differentiated to endothelial cells with blood-brain barrier (BBB) properties, as defined by high transendothelial electrical resistance (TEER), low passive permeability, active transporter functions. Typical protocols use undefined components, which impart unacceptable variability on the...