We function at the intersection of a variety of disciplines which include zebrafish development, drug discovery, and cardiovascular biology.
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. 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 heterotopic ossification, 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 evaluation.
2006 – Discovered the role of PI3K-ERK crosstalk in vascular development.
2008 – Discovered the first pharmacological inhibitor of the BMP pathway.
2010 – First large scale in vivo structure activity relationship (SAR) study outside the antimicrobial field.
2008, 2010 – First reported use of pharmacological inhibitors of BMP and Wnt pathways to induce cardiomyogenesis in pluripotent stem cells.
2008, 2011, 2013, 2014, 2015 – Helped reveal therapeutic potential of a BMP inhibitor for anemia, fibrodysplasia ossificans progressiva, atherosclerosis, and variety of cancers (lung, metastatic breast, ovarian and brain cancers).
2015 – Discovered phosphodiesterase-4 as a pharmacological target for hedgehog signaling inhibition.
2015 – Signed an exclusive research and licensing agreement with La Jolla Pharmaceutical Company covering novel BMP receptor inhibitors.
A major focus of lab's drug development efforts, begun with a generous support from the Cali Family Fund, remains finding a safe and effective treatment for fibrodysplasia ossificans progressiva (FOP), a rare genetic disease of progressive heterotopic ossification. To learn more about FOP, please check out this video by IFOPA.