Curative therapies for inherited blood disorders are becoming a reality. Our research asks the biological questions that determine whether those therapies are safe, durable, and effective for every patient. By combining functional genomics, genome editing, and stem cell biology, we discover the mechanisms that regulate fetal hemoglobin, preserve genome integrity, and improve the next generation of genetic therapies.
Discovering the biology of fetal hemoglobin regulation
Most infants with sickle cell disease appear healthy at birth because they naturally produce fetal hemoglobin, a form of hemoglobin that protects red blood cells from sickling. As fetal hemoglobin disappears during infancy and adult hemoglobin takes its place, disease symptoms begin. Understanding why this developmental switch occurs—and how to reverse it—offers one of the most promising paths toward durable therapies for sickle cell disease and β-thalassemia.
Our laboratory studies the genetic and epigenetic mechanisms that regulate fetal hemoglobin expression, including how genetic variants, regulatory DNA elements, transcription factors, and chromatin states control γ-globin silencing. We are particularly interested in understanding not only how much fetal hemoglobin is produced, but how it is distributed among individual red blood cells, since more uniform expression may provide greater protection from disease. Using functional genomics, single-cell sequencing, CUT&RUN, CUT&Tag, and CRISPR-based genome editing, we aim to discover the biology that enables safer and more effective therapies to reactivate fetal hemoglobin.
Our laboratory studies the genetic and epigenetic mechanisms that regulate fetal hemoglobin expression, including how genetic variants, regulatory DNA elements, transcription factors, and chromatin states control γ-globin silencing. We are particularly interested in understanding not only how much fetal hemoglobin is produced, but how it is distributed among individual red blood cells, since more uniform expression may provide greater protection from disease. Using functional genomics, single-cell sequencing, CUT&RUN, CUT&Tag, and CRISPR-based genome editing, we aim to discover the biology that enables safer and more effective therapies to reactivate fetal hemoglobin.
Genome integrity and clonal fate after therapeutic genome editing
Genome editing is transforming the treatment of inherited blood disorders by making it possible to correct disease-causing mutations in a patient's own blood stem cells. But editing a genome also means creating DNA breaks, and blood stem cells do not always repair those breaks perfectly. Some cells recover normally, while others acquire chromosome abnormalities or are naturally eliminated. Understanding what determines those different outcomes is essential for developing genetic therapies that remain safe and effective for a lifetime.
Our laboratory studies how blood stem cells respond to therapeutic genome editing, from the earliest DNA damage response through long-term clonal fate. We investigate how repair pathways influence chromosome stability, why some edited cells persist while others are eliminated, and how genome alterations such as micronuclei, aneuploidy, and chromothripsis arise. By combining functional genomics with molecular and cellular analyses, we aim to discover the biological mechanisms that determine the long-term safety of gene-edited stem cells.
Ultimately, our goal is not simply to catalog genome-editing outcomes, but to understand which alterations matter, how blood stem cells respond to them, and how that knowledge can guide the development of safer, more durable genetic therapies.
Our laboratory studies how blood stem cells respond to therapeutic genome editing, from the earliest DNA damage response through long-term clonal fate. We investigate how repair pathways influence chromosome stability, why some edited cells persist while others are eliminated, and how genome alterations such as micronuclei, aneuploidy, and chromothripsis arise. By combining functional genomics with molecular and cellular analyses, we aim to discover the biological mechanisms that determine the long-term safety of gene-edited stem cells.
Ultimately, our goal is not simply to catalog genome-editing outcomes, but to understand which alterations matter, how blood stem cells respond to them, and how that knowledge can guide the development of safer, more durable genetic therapies.