A5081451390- Hemoglobinopathies and Related Disorders
- Prenatal Screening and Diagnostics
- RNA modifications and cancer
- Iron Metabolism and Disorders
- CRISPR and Genetic Engineering
- Erythrocyte Function and Pathophysiology
- Kruppel-like factors research
- Cancer-related gene regulation
- Atherosclerosis and Cardiovascular Diseases
- ATP Synthase and ATPases Research
- Nanoplatforms for cancer theranostics
- RNA Research and Splicing
- Bioactive Compounds and Antitumor Agents
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Protein Tyrosine Phosphatases
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Systemic Sclerosis and Related Diseases
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Single-cell and spatial transcriptomics
Stanford University
2023-2024
UNSW Sydney
2014-2024
Reactivating the fetal globin gene Mutation of adult-type genes causes sickle cell disease and thalassemia. Although treating these hemoglobinopathies with therapy is possible, there a pressing need for pharmacologic approaches to treat general patient populations. One promising approach reactivate repressed expression fetal-type hemoglobin (HbF) in adult erythroid cells. Masuda et al. reveal molecular mechanism governing HbF repression as mediated by LRF/ZBTB7A transcription factor. The...
Regulatory DNA sequences within enhancers and promoters bind transcription factors to encode cell type-specific patterns of gene expression. However, the regulatory effects programmability such remain difficult map or predict because we have lacked scalable methods precisely edit quantify in an endogenous genomic context. Here present approach measure quantitative hundreds designed sequence variants on expression, by combining pooled CRISPR prime editing with RNA fluorescence
Abstract Objectives Hydroxyurea (HU) is the most widely used therapy for adults and children with sickle cell disease (SCD). It believed to act largely by inducing transcription of fetal γ-globin genes generate hemoglobin (HbF), which inhibits pathological polymerization (HbS). The mechanisms hydroxyurea elevates HbF are unclear. We explored hypothesis that induces expression inhibiting 2 gene repressors, BCL11A ZBTB7A (also known as LRF), normally bind promoters inhibit their after birth....
Krüppel-like Factor 3 (KLF3) is a broadly expressed zinc-finger transcriptional repressor with diverse biological roles. During erythropoiesis, KLF3 acts as feedback of set genes that are activated by 1 (KLF1). Noting KLF1 binds α-globin gene regulatory sequences during erythroid maturation, we sought to determine whether also interacts the locus regulate transcription. We found expression human transgenic reporter markedly up-regulated in fetal and adult cells Klf3−/− mice. Inspection mouse...
A hallmark of cancer cells is their ability to reprogram nutrient metabolism. Thus, disruption this phenotype a potential avenue for anti-cancer therapy. Herein we used phenotypic chemical library screening approach identify molecules that disrupted metabolism (by increasing cellular oxygen consumption rate) and were toxic cells. From screen discovered 1,4-Naphthoquinone (referred as BH10) broad range cell types. BH10 has improved cancer-selective toxicity compared doxorubicin, 17-AAG,...
Alternative splicing can lead to distinct protein isoforms. These have different functions in specific cells and tissues or developmental stages. In this study, we explored whether transcripts assembled from long read, nanopore-based, direct RNA-sequencing (RNA-seq) could improve the identification of isoforms human K562 cells. By comparing with Illumina-based short read RNA-seq, showed that a large proportion Ensembl (5949/14,326) genes expressing alternatively spliced (486/2981) identified...
Raynaud's syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis four cohorts discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, RAB6C) ADRA2A, IRX1 co-localized with expression quantitative trait (eQTLs), distal arteries. CRISPR gene editing further showed that ADRA2A NOS3 modified situ RNAscope clarified specificity of small vessels around capillaries skin. A functional...