A5054087528- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Hemoglobinopathies and Related Disorders
- Renal cell carcinoma treatment
- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
The Francis Crick Institute
2023-2025
University of Oxford
2021
MRC Weatherall Institute of Molecular Medicine
2021
Abstract To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and accurately quantify their functional effects. A gene exemplifying challenge variant interpretation von Hippel–Lindautumor suppressor ( VHL ). encodes an E3 ubiquitin ligase that regulates cellular response hypoxia. Germline pathogenic in predispose patients tumors including clear cell renal carcinoma (ccRCC) pheochromocytoma, somatic mutations are frequently...
Abstract The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, most common single gene disorders. Here, we address mechanisms regulating embryonically α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) open, acetylated chromatin interacts with α-globin...
ABSTRACT Understanding the effects of rare genetic variants remains challenging, both in coding and non-coding regions. While multiplexed assays variant effect (MAVEs) have enabled scalable functional assessment variants, established MAVEs are limited by either exogenous expression or constraints genome editing. Here, we introduce a pooled prime editing (PE) platform haploid human cells to scalably assay their endogenous context. We first optimized delivery HAP1 cells, defining optimal...
ABSTRACT To maximize the impact of precision medicine approaches, it is critical to accurately identify genetic variants in cancer-associated genes with functional consequences. Yet, our knowledge rare conferring clinically relevant phenotypes and mechanisms through which they act remains highly limited. A tumor suppressor gene exemplifying challenge variant interpretation VHL . encodes an E3 ubiquitin ligase that regulates cellular response hypoxia. Germline pathogenic predispose patients...