A5083128585- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Histone Deacetylase Inhibitors Research
- Neonatal Respiratory Health Research
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Hematopoietic Stem Cell Transplantation
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Medical Imaging and Pathology Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Zebrafish Biomedical Research Applications
- Renal and related cancers
- Cancer-related Molecular Pathways
- Childhood Cancer Survivors' Quality of Life
- Ethics and Legal Issues in Pediatric Healthcare
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- CRISPR and Genetic Engineering
- Hemoglobinopathies and Related Disorders
- Cancer Genomics and Diagnostics
Columbia University Irving Medical Center
2018-2019
New York University
2012-2018
Columbia University
2018
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2017
Howard Hughes Medical Institute
2012-2015
University School
2015
Cancer Institute (WIA)
2014
Rockefeller University
2011
The pathogenesis of idiopathic pulmonary fibrosis (IPF), an intractable interstitial lung disease, is unclear. Recessive mutations in some genes implicated Hermansky-Pudlak syndrome (HPS) cause HPS-associated pneumonia (HPSIP), a clinical entity that similar to IPF. We previously reported HPS1−/− embryonic stem cell-derived 3D organoids showed fibrotic changes. Here, we show the introduction all HPS associated with HPSIP promotes changes organoids, while deletion HPS8, which not HPSIP, does...
Abstract Purpose: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Chemotherapy treatments show high response rates but have debilitating effects carry risk of relapse. Previous work implicated NOTCH1 other oncogenes. However, direct inhibition these pathways affects healthy tissues cancer alike. Our goal in this has been to identify enzymes active T-ALL whose activity could be targeted for therapeutic purposes. Experimental Design: To...
Little is known on post-transcriptional regulation of adult and embryonic stem cell maintenance differentiation. Here we characterize the role Ddb1, a component CUL4-DDB1 ubiquitin ligase complex. Ddb1 highly expressed in multipotent hematopoietic progenitors its deletion leads to abrogation both fetal hematopoiesis, targeting specifically transiently amplifying progenitor subsets. However, non-dividing lymphocytes has no discernible phenotypes. silencing activates Trp53 pathway significant...
Although strategies for directed differentiation of human pluripotent stem cells (hPSCs) into lung and airway have been established, terminal maturation the remains a vexing problem. We show here that in Collagen I 3D cultures absence glycogen synthase kinase 3 (GSK3) inhibition, hPSC-derived progenitors (LPs) undergo multilineage proximal cells, type alveolar epithelial morphologically mature II cells. Enhanced cell cycling, one signaling outputs GSK3 plays role maturation-inhibiting effect...
Protein–protein interactions are typically identified by either biochemical purification coupled to mass spectrometry or genetic approaches exemplified the yeast two-hybrid assay; however, neither assay works well for identification of cofactors poorly soluble proteins. Solubility a protein is thought increase upon cofactor binding, possibly masking otherwise exposed hydrophobic domains. We have exploited this notion develop high-throughput screen identify interacting partners an insoluble...
PRDM16 is a transcriptional coregulator involved in translocations acute myeloblastic leukemia (AML), myelodysplastic syndromes, and T lymphoblastic that highly expressed required for the maintenance of hematopoietic stem cells (HSCs), can be aberrantly AML. Prdm16 as full-length (fPrdm16) short (sPrdm16) isoforms, latter lacking N-terminal PR domain. The role both isoforms normal malignant hematopoiesis unclear. We show here fPrdm16 was critical HSC maintenance, induced multiple genes...
Editing of adenosine (A) to inosine (I) at the first anticodon position in tRNA is catalyzed by deaminases acting on (ADATs). This essential reaction bacteria and eukarya permits a single decode multiple codons. Bacterial ADATa homodimer with two bound Zn(2+). The crystal structure revealed residues important for substrate binding catalysis; however, such high resolution structural information not available eukaryotic deaminases. Despite significant sequence similarity among deaminases, we...
Maintenance of stem cell plasticity is determined by the ability to balance opposing forces that control gene expression. Regulation transcriptional networks, signaling cues and chromatin-modifying mechanisms constitute crucial determinants tissue equilibrium. Histone modifications can affect chromatin compaction, therefore co-transcriptional events influence their deposition determine propensities toward quiescence, self-renewal, or specification. The Paf1 complex (Paf1C) a critical...
Although strategies for directed differentiation of human pluripotent stem cells (hPSCs) into lung and airway have been established, terminal maturation the remains a vexing problem. We show here that in Collagen I 3D cultures absence glycogen synthase kinase 3 (GSK3) inhibition, hPSC-derived progenitors (LPs) undergo multilineage proximal arranged pseudostratified epithelia, type alveolar epithelial morphologically mature II cells. Enhanced cell cycling, one signaling outputs GSK3 plays...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Treatments 1-6 show high response rates but have debilitating effects carry risk of relapse 5,7,8 . Previous work implicated NOTCH1 other oncogenes 1,2,9-20 However, direct inhibition these pathways affects healthy tissues cancer alike. Here, we demonstrate that ubiquitin-specific protease 7 (USP7) 21-32 controls growth by stabilizing the levels JMJD3 demethylase. USP7 overexpressed...
Idiopathic pulmonary fibrosis (IPF) is an intractable interstitial lung disease for which no curative treatment available except transplantation. Its pathogenesis unclear, but a role injury to type 2 alveolar epithelial cells hypothesized. Recessive mutations in some, not all genes implicated Hermansky-Pudlak Syndrome (HPS) cause HPS-associated pneumonia (HPSIP), clinical entity similar IPF. We previously reported that mutation HPS1 embryonic stem cells-derived 3D organoids caused fibrotic...