Hemoglobin switching is the developmental process where different globin genes are activated at specific stages. Around six months after birth, the fetal γ-globin genes are silenced and the adult β-globin gene is activated, which prompts symptoms of β-hemoglobinopathies like sickle cell disease and β-thalassemia. By studying this switching mechanism, we aim to develop therapies that reactivate γ-globin to treat these conditions. Our research focuses on the genetic elements involved in this switch and how this knowledge can inform genome editing strategies for effective treatments.

Our lab focuses on how blood stem cells respond to DNA damage, particularly from genome editing tools like CRISPR-Cas9. We found that genome editing with CRISPR in blood stem cells can cause significant chromosomal damage, including the formation of micronuclei and chromosome bridges. Micronuclei contain fragmented chromosomes and can lead to chromothripsis, a massive and chaotic rearrangement of chromosomes, which poses dangerous risks and can potentially lead to cancer. Our lab is focused on thorough safety studies in CRISPR-based gene therapies to mitigate these serious risks and ensure their safe application.