Our lab studies how genetic variation, genome editing, and stem cell biology intersect to shape blood development and disease. We focus on mechanisms that regulate globin gene expression and maintain genome stability in hematopoietic stem cells, with the goal of translating mechanistic insight into safer, more durable genetic therapies for inherited blood disorders.
Functional genomics of hemoglobin switching
Hemoglobin switching is the developmental transition from fetal γ-globin to adult β-globin that occurs in early infancy. When this switch takes place, symptoms of sickle cell disease and β-thalassemia begin to emerge. Understanding how and why γ-globin is silenced is therefore central to disease biology and therapeutic intervention, particularly because increasing total fetal hemoglobin alone does not always prevent disease complications.
Our lab studies the genetic and epigenetic mechanisms that control this transition, including how specific variants, regulatory elements, and chromatin states determine when γ-globin is turned off and how fetal hemoglobin is distributed across individual red blood cells. Using tools such as CUT&RUN, CUT&Tag, single-cell sequencing, and CRISPR editing, we aim to design therapies that safely and durably reactivate γ-globin while promoting more uniform, protective HbF distribution in β-hemoglobinopathies.
Genome stability in gene-edited blood stem cells
Gene editing introduces double-strand DNA breaks, but blood stem cells do not always repair these breaks cleanly. As a result, edited hematopoietic stem and progenitor cells can develop mitotic errors such as micronuclei, chromosome segregation defects, or long-term chromosomal alterations. Understanding how these errors arise and are resolved is essential for evaluating the long-term safety of gene-editing therapies.
Our lab studies how blood stem cells respond to editing-induced DNA damage, including which repair pathways protect against aneuploidy or chromothripsis and which edited cells persist versus those that are naturally eliminated. By defining the full spectrum of genome-stability risks associated with CRISPR-based therapies, this work aims to identify strategies that improve the safety, durability, and clinical reliability of gene-edited stem cells. Micronuclei in CD34 cells
Techniques and Approaches:
o Quantification and characterization of micronuclei and chromosomal aberrations in edited hematopoietic stem and progenitor cells
o Analysis of mitotic fidelity and cell fate following genome editing, including the persistence or elimination of genomically unstable cells
o Longitudinal assessment of genomic stability in edited stem cells during differentiation and hematopoietic reconstitution
We collaborate closely with clinical, computational, and genomics groups to translate discovery into therapy.
