Antonio Baldini, M.D.: Balancing Gene Haploinsufficiency by Targeting Chromatin: The Case of Tb x1 and Congenital Heart Disease

Dr. Baldini studies Tbx1, a gene that is haploinsufficient in DiGeorge syndrome, and encodes a transcription factor. The mutant phenotype is associated with congenital heart disease, among other developmental abnormalities. His group has shown that loss of Tbx1 causes heart defects by affecting proliferation and differentiation of cardiac progenitor cells (CPCs), but the mechanistic details are unclear.

In this talk, he will present their latest data about the mechanisms by which Tbx1 regulates its targets. Mechanistic information was used to design successful drug-based phenotypic rescue in mouse models. Genome-wide analyses identified genetic pathways rebalanced by the rescuing drug. These results have helped identify unexpected pathways that are helping us build novel hypotheses about the biology of CPCs.