Our Work
Understanding the origin and consequences of DNA damage in hematopoietic stem cells can reveal why marrow failure begins, why some patients progress to clonal evolution or malignancy, and where intervention may be most effective. By connecting basic mechanisms of genome maintenance to blood stem-cell biology and human disease, our lab aims to inform new preventive and therapeutic strategies for bone marrow failure syndromes.
01
Endogenous DNA damage in blood stem cells
A major goal of the lab is to identify the internal sources of DNA damage that accumulate in hematopoietic stem and progenitor cells under physiologic conditions. This includes studying how reactive aldehydes and other byproducts of normal metabolism create lesions that become particularly harmful when Fanconi anemia pathway function is impaired, as reflected in the lab’s work on ALDH9A1 deficiency and aldehyde-related genotoxic stress.
02
Fanconi anemia pathway and marrow vulnerability
The lab investigates why defects in the Fanconi anemia DNA repair pathway produce such profound hematologic consequences, from stem-cell depletion to marrow failure and cancer predisposition. This theme is supported by work defining genomic signatures of Fanconi anemia pathway deficiency in cancer, mechanistic studies of aldehyde detoxification dependencies, and clinical-genomic studies linking FANCB variant type with disease severity.
03
Stem-cell fate under genotoxic stress
DNA damage is not only a mutational event; it also changes how stem cells survive, age, and differentiate. The lab examines how genotoxic stress contributes to apoptosis, premature aging, loss of self-renewal, skewed lineage output, and exhaustion of the stem-cell compartment, themes also reflected in the group’s interest in marrow exhaustion and inflammatory stress responses.
04
Alcohol and aging
Alcohol metabolism generates reactive aldehydes that can damage DNA and place sustained stress on hematopoietic stem cells. We investigate how alcohol exposure interacts with aldehyde-detoxification and DNA-repair pathways to influence stem-cell survival, self-renewal, lineage differentiation, and premature aging.
