Brave New World
Dr. Sadek's research was featured in the fifth episode of Brave New World with Stephen Hawking.
Video courtesy of IWC Media/Channel 4.
We recently identified a brief window in early postnatal life during which the mammalian heart can undergo complete regeneration following various types of injury. This regenerative capacity is largely mediated through the proliferative competency of the pre-existing cardiomyocytes, and is lost by end of the first week of life.
This transient regenerative potential of the neonatal mouse heart provides a platform to study the molecular mechanisms that regulate mammalian heart regeneration. A major focus of our lab is to identify critical regulators of cardiomyocyte proliferation and cell cycle arrest in the neonatal heart, and discover new methods to reawaken cardiac regeneration in the adult mammalian heart.
Stem Cell Metabolism
Our lab has a long-standing interest in stem cell metabolism. We recently described the metabolic properties of both mouse and human hematopoietic stem cells (HSCs), which allowed us to develop a novel metabolic approach for stem cell enrichment from both the bone marrow and heart. Moreover, based on the unique metabolic footprint of glycolytic caerdiac progenitors, we were able to identify the epicardium and subepicardium of the heart as the cardiac hypoxic niche, which we believe houses resident cardiac progenitors.
These studies also helped us identify a transcriptional network involving Meis1, Pbx1, HoxA9, and the hypoxia master regulators Hif-1α and Hif-2α that regulates stem cell metabolism and quiescence. Future studies are focused on understanding the complex interplay between stem cell metabolism, quiescence, self-renewal, and cell fate decision.