A5043283285- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Platelet Disorders and Treatments
- Immune Cell Function and Interaction
- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Renal and related cancers
- Virus-based gene therapy research
- Hematopoietic Stem Cell Transplantation
- Genetics and Neurodevelopmental Disorders
- Blood groups and transfusion
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Retinal Development and Disorders
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Animal Genetics and Reproduction
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- T-cell and B-cell Immunology
- Liver physiology and pathology
- Prenatal Screening and Diagnostics
Children's Hospital of Philadelphia
2015-2024
University of Pennsylvania
2015-2024
Philadelphia University
2016-2019
Cellular Therapeutics (United Kingdom)
2019
Emory University Hospital
2012-2018
California University of Pennsylvania
2015-2016
Icahn School of Medicine at Mount Sinai
2005-2008
Institute of Immunology
2002-2004
The Wistar Institute
2000-2001
The establishment of the primitive streak and its derivative germ layers, mesoderm endoderm, are prerequisite steps in formation many tissues. To model these developmental stages vitro, an ES cell line was established that expresses CD4 from foxa2 locus addition to GFP brachyury locus. A GFP-Bry(+) population expressing variable levels CD4-Foxa2 developed upon differentiation this line. Analysis gene-expression patterns potential revealed CD4-Foxa2(hi)GFP-Bry(+) displays characteristics...
The members of the ADAR (adenosine deaminase acting on RNA) gene family are involved in site-selective RNA editing that changes adenosine residues target substrate RNAs to inosine. Analysis staged chimeric mouse embryos with a high contribution from embryonic stem cells functional null allele for ADAR1 revealed heterozygous embryonic-lethal phenotype. Most ADAR1+/- died before day 14 defects hematopoietic system. Our results suggest importance regulated levels expression, which is critical...
The development of methods to achieve efficient reprogramming human cells while avoiding the permanent presence transgenes represents a critical step toward use induced pluripotent stem (iPSC) for clinical purposes, such as disease modeling or reconstituting therapies. Although several exist generating iPSC free from mouse neonatal normal tissues, sufficiently system is still needed widespread derivation disease-specific humans with inherited degenerative diseases. Here, we report humanized...
We reported previously that well-characterized enhancers but not promoters for typical tissue-specific genes, including the classic Alb1 gene, contain unmethylated CpG dinucleotides and evidence of pioneer factor interactions in embryonic stem (ES) cells. These properties, which are distinct from bivalent histone modification domains characterize genes involved developmental decisions, raise possibility expressed only differentiated cells may need to be marked at pluripotent stage. Here, we...
Patients with Down syndrome (trisomy 21, T21) have hematologic abnormalities throughout life. Newborns frequently exhibit abnormal blood counts and a clonal preleukemia. Human T21 fetal livers contain expanded erythro-megakaryocytic precursors enhanced proliferative capacity. The impact of on the earliest stages embryonic hematopoiesis is unknown nearly impossible to examine in human subjects. We modeled yolk sac using induced pluripotent stem cells (iPSCs). Blood progenitor populations...
Induced pluripotent stem cells were created from a pancreas agenesis patient with mutation in GATA6. Using genome-editing technology, additional cell lines mutations both GATA6 alleles generated and demonstrated severe block definitive endoderm induction, which could be rescued by re-expression of several different GATA family members. the endodermal progenitor culture system to bypass developmental at stage, one or differentiated into β-like but reduced efficiency. Use suboptimal doses...
During development, erythroid cells are produced through at least 2 distinct hematopoietic waves (primitive and definitive), generating erythroblasts with different functional characteristics. Human induced pluripotent stem (iPSCs) can be used as a model platform to study the development of red blood (RBCs) many differentiation protocols after primitive wave hematopoiesis. Recent advances have established that definitive progenitors generated from iPSCs, creating unique situation for...
T lymphocytes express two Src tyrosine kinases, Lck and Fyn. While thymocyte cell subsets are largely normal in fyn−/− mice, animals lacking have impaired development. Here, it is shown that Fyn required for the rapid burst of interleukin (IL)-4 IL-13 synthesis, which occurs promptly after receptor activation. The lack cytokine induction fyn mutant mice due to a block natural killer (NK) Studies using bone marrow chimeras indicate defect behaves cell-autonomous manner, NK cells probably not...
We analyzed the role of Fyn tyrosine kinase in CNS myelination by using <i>fyn</i><sup>−/−</sup> null mutant mice, which express no protein. found a severe myelin deficit forebrain at all ages from 14 d to 1 year. The was maximal month age and similar regardless mouse strain background or whether it determined bulk isolation quantitation basic To determine cellular basis deficit, we counted oligodendrocytes tissue sections mice expressing oligodendrocyte-targeted β-galactosidase, used light...
NK T cells are a lymphocyte lineage that is selected by CD1d and characterized the ability to rapidly secrete large amounts of both IFN-gamma IL-4 after TCR stimulation. Using reactivity tetramers define presumptive cells, several cell progenitor populations were based upon marker expression CD4 vs CD8 expression. The earliest found be negative for markers could proliferate IL-7, while mature did not. NK1.1(-) progenitors capable up-regulating NK1.1 when transferred in vivo. Upon...
Induced pluripotent stem cells (iPSCs) provide an inexhaustible source of for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs iPSCs derived from diseased versus normal human cohorts as they emerge during in vitro directed differentiation. Using generated cohort carrying mutations (PiZZ) gene responsible alpha-1 antitrypsin (AAT) deficiency, find that global transcriptomes PiZZ diverge controls upon...
Through the ectopic expression of four transcription factors, Oct4, Klf4, Sox2 and cMyc, human somatic cells can be converted to a pluripotent state, generating so-called induced stem (iPSCs)1-4. Patient-specific iPSCs lack ethical concerns that surround embryonic (ESCs) would bypass possible immune rejection. Thus, have attracted considerable attention for disease modeling studies, screening pharmacological compounds, regenerative therapies5. We shown generation transgene-free from patients...
Choroideremia (CHM) is an X- linked retinal degeneration that symptomatic in the 1st or 2nd decade of life causing nyctalopia and loss peripheral vision. The disease progresses through mid-life, when most patients become blind. CHM a favorable target for gene augmentation therapy, as due to function protein necessary cell health, Rab Escort Protein 1 (REP1).The cDNA can be packaged recombinant adeno-associated virus (rAAV), which has established track record human therapy studies, and,...