Faqian Li, B.M., Ph.D.
University of South Dakota
Hubei Medical College, China
Department of Pathology and Laboratory Medicine
Congestive heart failure is a major health problem in developed countries and incidence increases as the population ages. Cardiac chamber dilatation and poor contractile performance is the structural and functional basis of heart pump dysfunction.
At the cellular level, chamber dilatation in cardiac failure is largely caused by excessive elongation of heart muscle cells with inadequate increase in cell diameter. The Li Laboratory is investigating the molecular mechanisms that regulate cardiac muscle cell shape change and structural remodeling during heart hypertrophy and failure.
Our findings have pointed to a key role for Wnt/β-catenin signaling in the transition from heart hypertrophy to failure. Currently, we are searching for β-catenin signaling targets and partners in heart muscle cells with the hope of identifying key molecules involved in the regulation of cardiac muscle cell shape for future therapeutic intervention.
The Li Laboratory found that mammalian heart muscle cells rapidly switched from proliferation to hypertrophy in neonatal period while the cells in other vertebrates like chicken continued to proliferate even in adults. Using animal models and explanted failing human hearts, we showed that Wnt/β-catenin signaling, an important developmental pathway, was upregulated during heart failure. This pathway can be explored as a potential therapeutic target.
Another impediment for cardiac repair and recovery from injuries is that the main functional cells, cardiac myocytes, lack significant regenerative potential. By investigating the molecular mechanism that control the transition of heart muscle cells from hyperplasia to hypertrophy, we aim at finding key pathways for novel interventions to promote cardiac regeneration. We are especially interested in epigenetic changes during this neonatal transition.
Epigenetics is a new frontier in biology, with far-reaching implications. Modifications of DNA and DNA binding proteins without any change in primary DNA sequences play important roles in aging, cancer, and many chronic diseases. We have shown that epigenetic changes can be used to diagnose and classify cancers.