A5022275842- Pluripotent Stem Cells Research
- Amyotrophic Lateral Sclerosis Research
- Tissue Engineering and Regenerative Medicine
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Neurogenetic and Muscular Disorders Research
- Neurogenesis and neuroplasticity mechanisms
- Cholinesterase and Neurodegenerative Diseases
- 3D Printing in Biomedical Research
- Parkinson's Disease Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- biodegradable polymer synthesis and properties
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Epigenetics and DNA Methylation
- Voice and Speech Disorders
- Electrospun Nanofibers in Biomedical Applications
- MicroRNA in disease regulation
- Cancer Treatment and Pharmacology
- Neurological disorders and treatments
- Galectins and Cancer Biology
- Cardiovascular Effects of Exercise
- Toxin Mechanisms and Immunotoxins
Clinical Research Institute
2024-2025
Harvard University
2024-2025
Massachusetts General Hospital
2024-2025
Memorial Sloan Kettering Cancer Center
2023-2024
Kettering University
2021-2022
Leiden University Medical Center
2017-2021
Leiden University
2021
Royal Netherlands Academy of Arts and Sciences
2017
University of Glasgow
2017
Wellcome/MRC Cambridge Stem Cell Institute
2016
Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and endothelial also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs MTs with CFs sarcomeric structures T-tubules, enhanced contractility, mitochondrial...
Cardiomyocytes and endothelial cells in the heart are close proximity constant dialogue. Endothelium regulates size of heart, supplies oxygen to myocardium secretes factors that support cardiomyocyte function. Robust predictive cardiac disease models faithfully recapitulate native human physiology vitro would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we generated characterized microtissues integrate both cell types complex 3D structures. We established...
Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and expansion neocortex. The in vitro generation oRG is essential to investigate underlying mechanisms human neocortical expansion. By activating STAT3 signaling pathway using leukemia inhibitory factor (LIF), which not expressed guided organoids, we define a organoid differentiation method from pluripotent stem (hPSCs) recapitulates pool into oSVZ. oSVZ...
Significance Anthracyclines like doxorubicin are anticancer drugs, used by over 1 million cancer patients annually. However, they cause severe side effects, most notably, cardiotoxicity and therapy-related malignancies. It is unclear whether these effects directly linked to their activity. Doxorubicin exerts two activities: DNA damage chromatin damage. Here, we show that both activities conspire in the cardiotoxicity, while variants with only chromatin-damaging activity remain active drugs...
Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods complex, lack robustness do not work in multiple cell types. Here we address these limitations by developing single-step optimized inducible knockdown or knockout (sOPTiKD sOPTiKO) platforms. These based on genetic engineering human genomic safe harbors combined with an improved tetracycline-inducible system CRISPR/Cas9 technology. We...
Human pluripotent stem cells (hPSCs) are widely used to study cardiovascular cell differentiation and function. Here, we induced of hPSCs (both embryonic induced) proepicardial/epicardial progenitor that cover the heart during development. Addition retinoic acid (RA) bone morphogenetic protein 4 (BMP4) promoted expression mesodermal marker PDGFRα, upregulated characteristic (pro)epicardial genes, downregulated transcription myocardial genes. We confirmed (pro)epicardial-like properties these...
Importance The etiology of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is unknown. However, neuroinflammation and complement activation may play role in disease progression. Objective To determine the effects zilucoplan, an inhibitor C5, individuals with ALS. Design, Setting, Participants Zilucoplan was tested as regimen A HEALEY ALS Platform Trial, phase 2 to 3 multicenter, randomized, double-blind, placebo-controlled perpetual platform clinical trial sharing...
RNS60 is an investigational product in clinical development for amyotrophic lateral sclerosis (ALS). slowed disease progression the ALS SOD1G93A mouse model and was safe well tolerated both open-label pilot study a randomized, placebo-controlled, multicenter phase 2 trial people living with ALS. The objective of this ongoing expanded access protocol (EAP) to provide who are ineligible controlled trials collect data on safety tolerability dosing via twice-daily nebulization rather than...
Abstract The formation of cardiac mesodermal subtypes is highly regulated in time and space during heart development. In vitro models based on human pluripotent stem cells (hPS cells) provide opportunities to study mechanisms underlying fate choices governing lineage specification from common cardiovascular progenitors embryos. generation endothelial particular allows the creation complex disorders which either cardiomyocytes or are affected. Here, a protocol for co‐differentiation mesoderm...
Human induced pluripotent stem cells (hiPSCs) and their derivative cardiomyocytes (hiPSC-CMs) have been successfully used to study the electrical phenotype of cardiac ion channel diseases. However, strategies mature CMs more comprehensive systems recapitulating heart complexity are required advance our ability capture adult phenotypes. We differentiated wild-type (WT) long QT syndrome type 1 (LQT1) hiPSCs into CMs, endothelial fibroblasts. The three cell types were combined form...
Abstract: Calreticulin, the main Ca 2+ binding protein in endoplasmic reticulum of eukaryotic cells, was characterized Ginkgo biloba L. pollen and seeds. Electrophoretic analysis partly purified extracts showed presence two bands 57 50kDa apparent molecular masses, which strongly cross‐reacted with antibodies against plant calreticulins. Amino acid sequence comparison other animal calreticulins revealed a much higher similarity N‐terminus homologue from angiosperms rather than that mammals....
Mammalian outer radial glia (oRG) emerge as cortical progenitor cells that directly support the development of an enlarged subventricular zone (oSVZ) and, in turn, expansion neocortex. The
Abstract Contraction of muscle reflects its physiological state. Methods to quantify contraction are often complex, expensive and tailored specific models or recording conditions, require specialist knowledge for data extraction. Here we describe an automated, open-source software tool (MUSCLEMOTION) adaptable use with standard laboratory clinical imaging equipment that enables quantitative analysis normal cardiac contraction, disease phenotypes pharmacological responses. MUSCLEMOTION...
Background: The KIR2.1 channel, by generating inward rectifier potassium current (IK1), is essential for a stable resting membrane potential and final repolarization.Aberrant expression, either increased or decreased, associates with several diseases such as Andersen-Tawil syndrome, short long QT syndromes.KIR2.1 ion channel trafficking anchoring depends on specific amino acid sequences.Purpose: We aimed to determine new functional domains within the C-terminus of protein combining...