Congratulations to Mandy!

Mandy just received her PhD in Molecular and Cellular Biology from UC Berkeley in August. Her dissertation “Flipping the Hemoglobin Switch and Discovering Regulators Involved in Fetal Hemoglobin Reactivation” can be found here: https://escholarship.org/uc/item/02m6p6v6
 
escholarship.orgescholarship.org
Author(s): Boontanrart, Mandy | Advisor(s): Corn, Jacob E | Abstract: The fetal to adult hemoglobin switch is a developmental process by which fetal hemoglobin becomes silenced after birth and replaced by adult hemoglobin. Diseases caused by defective or missing adult hemoglobin, such as Sickle Cell Disease or β-Thalassemia, can be ameliorated by reactivating fetal hemoglobin. We discovered that knockdown or knockout of β-globin, a subunit of adult hemoglobin, led to robust upregulation of γ-globin, a subunit of fetal hemoglobin. This phenomenon suggested that red blood cells have an inherent ability to upregulate fetal hemoglobin in the event that adult hemoglobin is lacking.We developed multiple gene-editing tools in an immortalized erythroid cell model to investigate the molecular mechanisms behind the increase in fetal hemoglobin. Time-course transcriptomics identified ATF4, a transcription factor, as a causal regulator of this response. Further analysis also converged upon downregulation of MYB and BCL11A, known repressors of γ-globin, described in detail in chapter 2. Further work in chapter 3 explores other possible fetal hemoglobin regulators as discovered by CRISPRi arrayed mediated knockdown experiments. This work furthers our understanding of fundamental mechanisms of gene regulation and how cellular and molecular events influence red blood cell differentiation.

SUBMIT A COMMENT

Your email address will not be published. Required fields are marked *

Filters

Latest News

January 23, 2023

Welcome to Alessandra!

Alessandra Albertelli received her Master’s degree in Medical Biotechnology and Molecular Medicine from the University of Milan in 2017. In her Master’s...

December 9, 2022

Welcome back Martina!

Martina received her MSc in Biology from ETH Zurich in September 2022. She worked in the Corn lab, focusing on the role of the ubiquitin-proteasome system in...

December 4, 2022

BASE EDITING AS A POTENTIAL CURE FOR FANCONI ANEMIA – PUBLISHED IN NATURE COMMUNICATIONS

Cas-mediated genome editing technology holds great promise as a curative treatment for a number of genetic diseases. Conventional CRISPR-Cas genome editing...

News Archive

Tweets