A5056001797- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Cleft Lip and Palate Research
- Chromatin Remodeling and Cancer
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Pancreatitis Pathology and Treatment
- Genetic and rare skin diseases.
- Monoclonal and Polyclonal Antibodies Research
- Congenital Heart Disease Studies
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Glycosylation and Glycoproteins Research
- Cancer and Skin Lesions
- Cellular transport and secretion
- RNA modifications and cancer
Broad Center
2019-2022
University of California, San Francisco
2019-2022
Cornell University
2010-2015
Kettering University
2013-2014
Memorial Sloan Kettering Cancer Center
2010-2011
Astrocytes are an essential component of the CNS, and recent evidence points to increasing diversity their functions. Identifying molecular pathways that mediate distinct astrocyte functions, is key understanding how nervous system operates in intact pathological states. In this study, we demonstrate Hedgehog (Hh) pathway, well known for its roles developing active astrocytes mature mouse forebrain vivo . Using multiple genetic approaches, show regionally subsets receive Hh signaling,...
Sonic hedgehog (SHH), a key regulator of embryonic neurogenesis, signals directly to neural stem cells (NSCs) in the subventricular zone (SVZ) and astrocytes adult mouse forebrain. The specific mechanism by which GLI2 GLI3 transcriptional activators (GLI2 A ) repressors R carry out SHH signaling has not been addressed. We found that majority slow-cycling NSCs express Gli2 Gli3, whereas Gli1 is restricted ventrally all three genes are downregulated when transition into proliferating...
The touch dome is a highly patterned mechanosensory structure in the epidermis composed of specialized keratinocytes juxtaposition with innervated Merkel cells. epithelium maintained by tissue-specific stem cells, but signals that regulate are not known. We identify cells unique among epidermal their activated Hedgehog signaling and ability to maintain as distinct lineage compartment. Skin denervation reveals renewal requires perineural microenvironment, deleting Sonic hedgehog (Shh) neurons...
The syndromic autism spectrum disorder (ASD) Timothy syndrome (TS) is caused by a point mutation in the alternatively spliced exon 8A of calcium channel Cav1.2. Using mouse brain and human induced pluripotent stem cells (iPSCs), we provide evidence that TS prevents normal developmental switch Cav1.2 utilization, resulting persistent expression gain-of-function mutant channels during neuronal differentiation. In iPSC models, reduces abundance SATB2-expressing cortical projection neurons,...
mSWI/SNF or BAF chromatin regulatory complexes are dosage-sensitive regulators of human neural development frequently mutated in autism spectrum disorders and intellectual disability. Cell cycle exit differentiation stem/progenitor cells is accompanied by subunit switching to generate neuron-specific nBAF complexes. We manipulated the timing exchange vivo found that early loss npBAF BAF53a stalls cell disrupt neurogenesis. Loss results decreased accessibility at specific transcription factor...
The blood-brain barrier (BBB) largely excludes antibodies from entering the central nervous system, thus limiting potential of therapeutic to treat conditions such as neurodegenerative diseases and neuro-psychiatric disorders. Here, we demonstrate that transport human across BBB in mice can be enhanced by modulating their interactions with neonatal Fc receptor (FcRn). When M252Y/S254T/T246E substitutions are introduced on antibody domain, immunohistochemical assays reveal widespread...
Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare and devastating childhood-onset lysosomal storage disease caused by complete loss of function the hydrolase α-N-acetylglucosaminidase. The lack functional enzyme in MPS patients leads to progressive accumulation heparan sulfate throughout body triggers cascade neuroinflammatory other biochemical processes ultimately resulting severe mental impairment early death adolescence or young adulthood. low prevalence severity has necessitated use...
ABSTRACT Nervous system development is orchestrated by tightly-regulated progenitor cell divisions, followed differentiation at precise but varying times across different regions. As progenitors exit the cycle, they initiate a subunit switch of mSWI/SNF or npBAF complex to generate neuron-specific nBAF complexes. These chromatin regulatory complexes play dosage-sensitive roles in neural and are frequently mutated neurodevelopmental disorders. Here we manipulated timing BAF exchange...