Junying Yuan, PhD, Harvard University

Junying Yuan made critical contributions to our understanding of apoptosis and necroptosis, two fundamental mechanisms that regulate the survival and death of mammalian cells. Her Ph.D. work, as a student at the Harvard Medical School and conducted in the laboratory of H. Robert Horvitz at the Massachusetts Institute of Technology, provided the first insight into the mechanism of programmed cell death in the nematode C. elegans. Yuan started her own lab in 1990 at the Cardiovascular Research Center, Massachusetts General Hospital, to test her hypothesis that a similar programmed cell death mechanism might exist in mammalian cells. Her daring hypothesis was proved two years later when her laboratory demonstrated that the mammalian interleukin-1b converting enzyme (later named caspase-1) is a functional homologue of C. elegans cell death gene product Ced-3 (Miura et al. 1993) and inhibition of caspase activation blocks neuronal cell death induced by trophic factor deprivation (Gagliardini et al. 1994). These works provided the first insight into the molecular mechanism that regulates apoptosis in mammalian cells. Subsequently, after her move in 1996 to Department of Cell Biology, Harvard Medical School, Yuan lab discovered necroptosis, a regulated necrotic cell death mechanism, and the role of RIPK1 kinase as a key mediator of necroptosis (Degterev et al. 2005, Degterev et al. 2008). This discovery overturned the traditional dogma that necrosis can only be a form of unregulated passive cell death and demonstrated the possibility of inhibiting necrotic cell death in multiple forms of degenerative and inflammatory human diseases. A small molecule inhibitor of RIPK1 kinase (Nec-1) discovered by Yuan lab is currently in preparation for a human clinical trial targeting neurodegenerative disease.