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Research

Our research can be divided into 2 broad areas. The first area involves chemical biology of vertebrate development, which entails discovery of small molecules that selectively modulate signaling pathways involved in embryogenesis. Because developmental pathways represent important untapped therapeutic targets, we have an active medicinal chemistry program to develop our novel small molecules as lead compounds for future therapies. We have thus far discovered potent and highly selective chemical modifiers of bone morphogenetic protein (BMP), Wnt, Hedgehog, and lipid signaling pathways, among others. Several of our compounds are first-in-class molecules with substantial therapeutic potential in rare and common diseases, including cancers, atherosclerosis and heart failure.  Thus, our chemical biological exploration is leading to new opportunities for innovative therapeutic programs.

In the second, we are exploring the potential of patient-derived induced pluripotent stem cells (iPSC) to study and treat human heart diseases. We use human iPSCs as renewable cell sources for examining the fundamental cell biology and physiology of normal and diseased human cardiomyocytes. Finally, we collaborate with bioengineers to develop human iPSC-derived heart tissues as a platform for drug discovery and testing, including validation of novel cardiac inotropes.

Chemical Genetics

Chemical Genetics of Embryonic Development

Fish and screen

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 interdisciplinary chemical genetic approach, we have discovered exquisitely selective modulators of the Bone Morphogenetic Protein (BMP), Wnt and Hedgehog pathways, as well as important new signaling components that direct early vertebrate development.

In addition, we have launched the Chemical Phenomics Initiative, through which we are making our chemical genetic tools available to the public with the goal of fostering collaborations, and accelerating discovery and translation.

For more information, visit Chemical Phenomics Initiative.

Therapeutic Discovery

Regenerative Chemical Biology

Human Cardiomyocyte Biology

Data Science

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