A5030737144- Pluripotent Stem Cells Research
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- Bipolar Disorder and Treatment
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
- Hereditary Neurological Disorders
- Nuclear Receptors and Signaling
- Genetics, Aging, and Longevity in Model Organisms
- Adipose Tissue and Metabolism
- 3D Printing in Biomedical Research
- Porphyrin Metabolism and Disorders
- Advanced Proteomics Techniques and Applications
- Electrospun Nanofibers in Biomedical Applications
- FOXO transcription factor regulation
- Renal and related cancers
- Microfluidic and Capillary Electrophoresis Applications
- Air Quality Monitoring and Forecasting
- RNA regulation and disease
- Glycosylation and Glycoproteins Research
- Amyotrophic Lateral Sclerosis Research
Salk Institute for Biological Studies
2009-2018
Boston Children's Hospital
2008-2014
Harvard University
2009-2014
University of California, San Diego
2009-2013
Dana-Farber Cancer Institute
2009
Brigham and Women's Hospital
2009
Physiopathologie et Epidémiologie des Maladies Respiratoires
2006
Canadian Red Cross Society
1992
The aggregation of proteins into oligomers and amyloid fibrils is characteristic several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process α-synuclein (α-syn) from monomers, via oligomeric intermediates, considered disease-causative toxic mechanism. We developed α-syn mutants that promote oligomer or fibril formation tested toxicity these by using a rat lentivirus system to investigate loss dopaminergic neurons in substantia nigra. most severe nigra observed...
How metabolism is reprogrammed during neuronal differentiation unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks transition aerobic glycolysis neural progenitor cells (NPC) oxidative phosphorylation. The protein levels c-MYC N-MYC, transcriptional activators HK2 LDHA genes, decrease dramatically. Constitutive expression leads cell death, indicating shut-off...
Significance Neuronal cultures are very valuable to learn about basic principles of the nervous system. In vivo, neural electrical activity is essence system function, controlling emotion, memory, sensory modalities, and behavior. this study, we discovered that many crucial neurophysiological properties were strongly altered in classic culture media widely used by research community. To overcome problem, designed tested a new tissue neuromedium adequately supports vitro neuronal activity....
mTOR inhibition is beneficial in neurodegenerative disease models and its effects are often attributable to the modulation of autophagy anti-apoptosis. Here, we report a neglected but important bioenergetic effect neurons. by rapamycin significantly preserves neuronal ATP levels, particularly when oxidative phosphorylation impaired, such as neurons treated with mitochondrial inhibitors, or derived from maternally inherited Leigh syndrome (MILS) patient iPS cells synthase deficiency....
The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, most frequent cause HSP. To understand how mutations SPG4 affect human neurons, we generated induced pluripotent stem cells (hiPSCs) from fibroblasts two patients carrying c.1684C>T nonsense mutation controls. These control hiPSCs were able to differentiate into neurons glia at...
α-Synuclein has been reported to be important in modulating brain plasticity and a key protein neurodegenerative diseases, including Lewy body dementia (LBD). We investigated how α-synuclein levels modulate adult neurogenesis the development of dendritic arborization spines dentate gyrus, which new neurons are constantly added. In human hippocampus, endogenous were increased LBD, numbers SOX2-positive cells decreased. whether newly generated modulated by α-synuclein, we found α/β-synuclein...
Mitochondria are a major target for aging and instrumental in the age-dependent deterioration of human brain, but studying mitochondria neurons has been challenging. Direct fibroblast-to-induced neuron (iN) conversion yields functional that retain important signs aging, contrast to iPSC differentiation. Here, we analyzed mitochondrial features iNs from individuals different ages. old donors display decreased oxidative phosphorylation (OXPHOS)-related gene expression, impaired axonal...
Characterization of signaling pathways in embryonic stem cells is a prerequisite for future application these to treat human disease and other disorders. Identification tyrosine cascades particular interest but complicated by the relatively low levels phosphorylation cells. These hurdles correlate with primary limitations mass spectrometry-based proteomics; namely, poor detection limit dynamic range. To overcome obstacles, we fabricated miniaturized LC-electrospray assemblies that provided...
Proteostasis is critical for maintaining cell function and proteome stability may play an important role in human embryonic stem (hESC) immortality. Notably, hESC populations exhibit a high assembly of active proteasomes, key node the proteostasis network. FOXO4, insulin/IGF-1 responsive transcription factor, regulates proteasome activity hESCs. We find that loss FOXO4 reduces potential hESCs to differentiate into neural lineages. Therefore, crosses evolutionary boundaries links invertebrate...
Objective Mutations in the spastic paraplegia gene 11 (SPG11), encoding spatacsin, cause most frequent form of autosomal‐recessive complex hereditary (HSP) and juvenile‐onset amyotrophic lateral sclerosis (ALS5). When SPG11 is mutated, patients frequently present with paraparesis, a thin corpus callosum, cognitive impairment. We previously delineated neurodegenerative phenotype neurons these patients. In current study, we recapitulated early developmental phenotypes outlined their cellular...
Abstract Here we describe protocols for the dopaminergic differentiation of pluripotent stem cells. We have optimized and compared two distinct protocols, both which are chemically defined applicable to embryonic induced First, present a five‐step method based on rosette formation (Basic Protocol 1); then monolayer paradigm inhibition alternate developmental pathways 2). Directed cells into specific cell types is crucial step towards understanding human development realizing biomedical...
Human embryonic stem cells (hESCs) can be cultured abundantly and indefinitely, but are subject to accumulations of chromosomal aberrations. To preserve their genetic integrity, hESCs commonly maintained as cell aggregates or clumps during passaging. However, clump passaging hinders large-scale culture complicates the isolation single clones. facilitate genetically modified clones while preserving we employed trypsin single-cell for brief periods before returning long-term maintenance. We...
We have previously described the isolation of two hybridoma variants secreting higher avidity IgM (D5 and 7F5), starting from E11 cell line, which produces an antibody specific for A Ag ABO blood group system. In order to explain at molecular level this increased reactivity, cDNA encoding H L chains E11, D5, 7F5 mAb were cloned sequenced. Comparison nucleotide sequences showed a single point mutation in each produced by variants. The mutations both located chain C region caused Ser Phe...