RT signatures of premature aging
Replication timing is a highly stable genomic property, is cell type-specific and highly conserved but altered in disease. In our lab, we exploit genome-wide RT characterization to identify disease abnormalities.
Particularly, we are interested in a family of rare genetic disorders colectively known as premature aging diseases. The most studied is Hutchinson-Gilford Progeria Syndrome (HGPS) caused by a point mutation in a component of the nuclear lamina. However, this family of diseases also includes many other syndromes that disrupt DNA repair, such as Werner, Rothmund-Thomson, Xeroderma Pigmentosum and Fanconi Anemia syndromes. Despite identification of causal mutations, there is no cure and children continue to die prematurely.
We identified a RT signature of premature aging syndromes. The premature aging-specific RT signature identified genomic regions that replicate late in normal cells derived from healthy donors of distinct ages but change to early replication in the disease. Work in our laboratoy is aimed to understand the developmental alterations in premature aging and its links to natural aging.
RT alterations in pediatric leukemia
The most common type of childhood cancer is acute lymphoblastic leukemia from B-cell lineage (B-ALL). Althoug distinct chromosomal abnormalities have been identified linked to specific types of B-ALL the causes remain poorly understood.
In this work, we exploited our RT signatures identification method to identify alterations in patients with pediatric leukemia.
We detected RT alterations associated with specific subtypes of B-ALL. Moreover, we performed a comparative analysis of RT programs of multiple B-ALL patients and distinct stages of B-cell development. Our findings suggest that B-ALL originates at specific stages of B-cell differentiation.