Chemical Biology of embryonic development and stem cell differentiation
The Hong laboratory is focused on Chemical Biology of vertebrate development and stem cell differentiation.
1) Chemical Genetics of Embryonic Development: In a manner analogous to classic mutagenesis screens, we conduct high-throughput chemical screens using zebrafish to discover small molecules that specifically perturb embryonic pattern formation. Using the chemical genetic approach, incorporating molecular cell biology, embryology, biochemistry, and medicinal chemistry, we have discovered exquisitely selective modulators of the Bone Morphogenetic Protein (BMP), Wnt, Innate Immunity and Hedgehog pathways, as well as important new signaling components that direct early vertebrate development.
2) Regenerative Chemical Biology: Since small molecules that perturb embryonic patterning do so by promoting development of specific cell types, we predict that they will be valuable chemical reagents for stem cell research and cell-based regenerative therapies. For example, our small molecules are widely used for robust induction of cardiomyogenesis and neurogenesis in pluripotent stem cells.
3) Drug Discovery/ Experimental Therapeutics: Developmental pathways represent important untapped therapeutic targets. We are using our novel small molecules as in vivo probes to discover future therapies. For example, we have made key contributions to the elucidation of BMP signaling as a promising therapeutic target for anemia of chronic disease, heterotopic ossification syndromes, inflammatory bowel disease, and atherosclerosis. Finally, we have discovered novel inotropes with unique mechanism of action that significantly improve cardiac function in mammals without triggering maladaptive changes.
The Center for Inherited Heart Disease collects clinical and genetic information that may help identify factors that influence cardiovascular disease progression and clinical outcomes in affected families. We also seek to discover new mutations that cause cardiovascular diseases. We maintain a repository of explanted human heart tissue samples as a resource for researchers. Our long-term goal is to help develop optimal "personalized care" for patients with familial cardiovascular diseases.