A5075136818- Genetics and Neurodevelopmental Disorders
- DNA Repair Mechanisms
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Estrogen and related hormone effects
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Genomics, phytochemicals, and oxidative stress
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Wnt/β-catenin signaling in development and cancer
- Hippo pathway signaling and YAP/TAZ
- Sirtuins and Resveratrol in Medicine
- RNA regulation and disease
- Calcium signaling and nucleotide metabolism
- Retinoids in leukemia and cellular processes
- Circular RNAs in diseases
- TGF-β signaling in diseases
- Glutathione Transferases and Polymorphisms
- Cancer-related Molecular Pathways
- Toxin Mechanisms and Immunotoxins
- Bacterial Genetics and Biotechnology
- NF-κB Signaling Pathways
- PARP inhibition in cancer therapy
- Protein Degradation and Inhibitors
Fred Hutch Cancer Center
2009-2021
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2014-2018
Cancer Research Center
2018
Case Western Reserve University
2006-2012
University of Washington
2009-2011
Case Comprehensive Cancer Center
2006
KAP1/TIF1 is proposed to be a universal corepressor protein for the KRAB zinc finger (KRAB-zfp) superfamily of transcriptional repressors.To characterize role KAP1 and KAP1-interacting proteins in repression, we investigated regulation stably integrated reporter transgenes by hormoneresponsive repressor proteins.Here, demonstrate that depletion endogenous levels small interfering RNA (siRNA) significantly inhibited KRAB-mediated repression chromatin template.Similarly, reduction cellular...
Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging eukaryotic cells. In an effort to identify small molecule inhibitors sirtuins for potential use as chemotherapeutics well tools modulate sirtuin activity, we previously identified nonselective inhibitor called cambinol (IC50 ≈ 50 μM SIRT1 SIRT2) with vitro vivo antilymphoma activity. the current study, used saturation transfer difference (STD)...
Rett syndrome (RS) is a debilitating neurological disorder affecting mostly girls with heterozygous mutations in the gene encoding methyl-CpG-binding protein MeCP2 on X chromosome. Because restoration of expression mouse model reverses neurologic deficits adult animals, reactivation wild-type copy inactive chromosome (Xi) presents therapeutic opportunity RS. To identify genes involved silencing, we screened library 60,000 shRNAs using cell line reporter Xi and found 30 clustered seven...
The long noncoding RNA Xist is critical for initiation and establishment of X-chromosome inactivation during embryogenesis in mammals, but it unclear whether its continued expression required maintaining X-inactivation vivo. By using an inactive X-chromosome-linked MeCP2-GFP reporter, which allowed us to enumerate reactivation events the mouse brain even when they occur very few cells, we found that deletion after leads 2–5% neurons a smaller fraction astrocytes. In contrast global loss both...
The spatio-temporal program of genome replication across eukaryotes is thought to be driven both by the uneven loading pre-replication complexes (pre-RCs) at onset S-phase, and differences in timing activation these during S phase. To determine degree which distribution pre-RC alone could account for chromosomal patterns, we mapped binding sites Mcm2-7 helicase complex (MCM) budding yeast, fission mouse humans. We observed similar individual MCM double-hexamer (DH) footprints species, but...
Cell polarity plays a critical role in the development of all metazoans; however, mechanisms cell and specific pathways mammalian organisms are still poorly understood. Lethal giant larvae (Lgl) is an apical-basal gene identified Drosophila, where it functions as tumor suppressor controlling self-renewal differentiation progenitor cells. There two orthologs Lgl genomes: Llgl1 Llgl2. While Lgls assumed to be genes, little known about their function vivo. Here we report functional analysis...
Genetic ablation as well pharmacological inhibition of sirtuin 2 (SIRT2), an NAD+-dependent protein deacylase, have therapeutic effects in various cancers and neurodegenerative diseases. Previously, we described the discovery a dual SIRT1/SIRT2 inhibitor called cambinol (IC50 56 59 µM, respectively), which showed cytotoxic activity against cancer cells vitro marked anti-proliferative effect Burkitt lymphoma mouse xenograft model. A number recent studies shown protective SIRT1 SIRT3 metabolic...
Abstract The spatio-temporal program of genome replication across eukaryotes is thought to be driven both by the uneven loading pre-replication complexes (pre-RCs) at onset S-phase, and differences in timing activation these during S-phase. To determine degree which distribution pre-RC alone could account for chromosomal patterns, we mapped binding sites Mcm2-7 helicase complex (MCM) budding yeast, fission mouse humans. We observed identical MCM double-hexamer footprints species, but notable...
Forward genetic screens using reporter genes inserted into the heterochromatin have been extensively used to investigate mechanisms of epigenetic control in model organisms. Technologies including short hairpin RNAs (shRNAs) and clustered regularly interspaced palindromic repeats (CRISPR) enabled such diploid mammalian cells. Here we describe a large-scale shRNA screen for regulators X-chromosome inactivation (XCI), murine cell line with firefly luciferase hygromycin resistance knocked at...
Rett Syndrome is a X‐linked brain disorder caused by mutation in one copy of the MeCP2 gene. This gene only expressed some cells due to X‐chromosome silencing, phenomenon that occurs all with two X chromosomes. After four cell divisions, each embryo randomly inactivates (Xi) and other (Xa) provides genetic code for cell. choice propagated through subsequent divisions. The exact mechanism initiation maintenance silencing unknown, but factors are known. Xist RNA coats Xi, acting as signal...
Forward genetic screens using reporter genes inserted into the heterochromatin have been extensively used to investigate mechanisms of epigenetic control in model organisms. Technologies including short hairpin RNAs (shRNAs) and clustered regularly interspaced palindromic repeats (CRISPR) enabled such diploid mammalian cells. Here we describe a large-scale shRNA screen for regulators X-chromosome inactivation (XCI), murine cell line with firefly luciferase hygromycin resistance knocked at...