A5037411730- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Hemoglobinopathies and Related Disorders
- RNA modifications and cancer
- Iron Metabolism and Disorders
- RNA Research and Splicing
- Erythrocyte Function and Pathophysiology
- Advanced Memory and Neural Computing
- Genomics and Chromatin Dynamics
- Microbial infections and disease research
- Genetics, Aging, and Longevity in Model Organisms
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Signaling Pathways in Disease
- RNA regulation and disease
- Epigenetics and DNA Methylation
- Blood groups and transfusion
- Reproductive tract infections research
- Fungal Plant Pathogen Control
- Monoclonal and Polyclonal Antibodies Research
- DNA and Nucleic Acid Chemistry
- Bacteriophages and microbial interactions
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2023-2024
Harvard University
2023-2024
Howard Hughes Medical Institute
2024
Boston Children's Hospital
2023-2024
Chinese Academy of Sciences
2015-2018
Institute of Biophysics
2015-2018
University of Chinese Academy of Sciences
2015-2017
Transcription factors (TFs) control numerous genes that are directly relevant to many human disorders. However, developing specific reagents targeting TFs within intact cells is challenging due the presence of highly disordered regions these proteins. Intracellular antibodies offer opportunities probe protein function and validate therapeutic targets. Here, we describe optimization nanobodies for BCL11A, a validated target treatment hemoglobin We obtained first-generation directed region...
Down-regulation of BCL11A protein reverses the fetal (HbF, α 2 γ ) to adult (HbA, β hemoglobin switch and is exploited in gene-based therapy for disorders. Because reliance on ex vivo cell manipulation marrow transplant, such therapies cannot lessen disease burden. To develop new small-molecule approaches, we investigated state erythroid cells. We report that tetramer formation mediated by a single zinc finger (ZnF0) required production steady-state protein. Beyond its role stability,...
The transcription factor BCL11A is a critical regulator of the switch from fetal hemoglobin (HbF: α2γ2) to adult (HbA: α2β2) during development. binds at cognate recognition site (TGACCA) in γ-globin gene promoter and represses its expression. DNA-binding mediated by triple zinc finger domain, designated ZnF456. Here, we report comprehensive investigation ZnF456, leveraging X-ray crystallography NMR determine structures both presence absence DNA. We delve into dynamics mode interaction with...
The transcription factor BCL11A is a critical regulator of the switch from fetal hemoglobin (HbF: α2γ2) to adult (HbA: α2β2) during development. binds at cognate recognition site (TGACCA) in γ-globin gene promoter and represses its expression. DNA-binding mediated by triple zinc finger domain, designated ZnF456. Here, we report comprehensive investigation ZnF456, leveraging X-ray crystallography NMR determine structures both presence absence DNA. We delve into dynamics mode interaction with...