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.

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