Speaker

Yingzi Yang

Time

2024.04.17 16:00-17:30

Abstract

Identifying the cellular and molecular mechanisms underlying genetic diseases provides invaluable insights into normal functions of genes and signaling pathways. By understanding genetic forms of heterotopic ossification (HO), which is pathological bone formation in soft tissues, we identified a self-amplifying, self-propagating loop of Yes-associated protein (YAP)–Sonic hedgehog (SHH) as a core molecular mechanism underlying diverse forms of HO. This self-propagating positive feedback loop was both necessary and sufficient for HO expansion and could act independently of Gnas in fibrodysplasia ossificans progressiva (FOP), another genetic HO, and nonhereditary HO mouse models. Genetic or pharmacological inhibition of YAP or SHH abolished HO without affecting normal bone homeostasis, providing a previously unrecognized therapeutic rationale to prevent, reduce, and shrink HO. We then went on to show that in the developing neural tube (NT), Yap, a key mechanosensor and mechanotransducer,is both necessary and sufficient in biochemical signaling activation during formation of notochord and floor plate, the ventral signaling centers that pattern the dorsal-ventral axis of NT and the surrounding tissues. We showed that Yap activation by a gradient of mechanical stress and tissue stiffness in the notochord and ventral NT induces FoxA2 and Shh expression. Mechanotransduction via Yap activation acts in feedforward mechanisms to induce FoxA2 expression for notochord formation and activate Shh expression for floor plate induction by synergistically interacting with FoxA2.

Bio

Professror Yang，received her undergraduate degree from Fudan University, PhD from Cornell University, and Postdoctoral Fellowship from Harvard University. She is currently the Associate Dean of the Harvard School of Dental Medicine, and was a longtime senior researcher at the NIH International Human Genome Research Institute. She has been working on cell biology and signaling pathways, and has made outstanding contributions to the molecular mechanisms of skeletal system and liver diseases. Her research results have been published in Nature, Nature Medicine, Dev Cell, J Clin Invest, PNAS and other top international journals as corresponding author. She received the 2006 NIH Award of Merit,2011 NIH APAO Outstanding Achievements and Merit Scholarship Award, 2022 President, Chinese Biological Investigators Society,2023 IADR Distinguished Scientist Award for Basic Research in Biological Mineralization,2024 AAAS Fellow.