Welcome to the lab!
In the Doerfler lab, we study how genetic variants shape disease, how gene-editing tools repair or introduce DNA changes, and how blood stem cells maintain genomic stability. Our work seeks to make gene and cell therapies safer, more effective, and more durable.
The Doerfler Lab uses interventional genomics to understand and treat inherited blood disorders. For us that means two things:
1. Understanding how genetic variants control fetal hemoglobin and influence sickle cell outcomes.
We study why people with sickle cell disease can have high total fetal hemoglobin (HbF) yet still experience pain crises, and how differences in HbF regulation, regulatory element deletions, and epigenetic wiring shape those outcomes.
Using tools like CUT&RUN, CUT&Tag, single-cell sequencing, and CRISPR editing, we map the DNA elements that decide which blood cells turn on fetal hemoglobin and how evenly it's distributed. This helps explain patient-to-patient differences and guides more precise, durable HbF-elevating therapies.
2. Investigating how genome editing affects DNA damage responses and chromosome stability in stem cells.
Gene editing functions by introducing double-strand DNA breaks, but stem cells don't always repair those breaks perfectly. Our lab studies what happens to hematopoietic stem and progenitor cells after editing--how often they form micronuclei or chromosome segregation errors, which DNA repair pathways protect them from aneuploidy or chromothripsis, and which edited cells persist versus those that are naturally eliminated.
We study why people with sickle cell disease can have high total fetal hemoglobin (HbF) yet still experience pain crises, and how differences in HbF regulation, regulatory element deletions, and epigenetic wiring shape those outcomes.
Using tools like CUT&RUN, CUT&Tag, single-cell sequencing, and CRISPR editing, we map the DNA elements that decide which blood cells turn on fetal hemoglobin and how evenly it's distributed. This helps explain patient-to-patient differences and guides more precise, durable HbF-elevating therapies.
2. Investigating how genome editing affects DNA damage responses and chromosome stability in stem cells.
Gene editing functions by introducing double-strand DNA breaks, but stem cells don't always repair those breaks perfectly. Our lab studies what happens to hematopoietic stem and progenitor cells after editing--how often they form micronuclei or chromosome segregation errors, which DNA repair pathways protect them from aneuploidy or chromothripsis, and which edited cells persist versus those that are naturally eliminated.
Why we do what we do:
Our goal is simple: to make curative therapies for sickle cell disease and other hematologic disorders safer and more accessible.
By understanding both the biology of hemoglobin switching and the biology of genome stability, we can design gene-editing approaches that work better, last longer, and carry fewer risks.
Interested in joining or rotating? Email pdoerfler@veriti.org