Junying Yuan

About

Junying Yuan is the Elizabeth D. Hay Professor of Cell Biology at Harvard Medical School. Her laboratory focuses on understanding the mechanisms of neurodegeneration, addressing the basic mechanisms of cell death and their implications in neurodegenerative diseases through cellular, genetic, molecular, and chemical biological approaches. Her research has identified the role of the unfolded protein response (UPR) as a cellular stress response to the accumulation of unfolded proteins in the endoplasmic reticulum, which plays an important role in mediating neurodegeneration. Yuan's work includes discovering that caspase-12 is specifically expressed in the endoplasmic reticulum and that its deficiency renders cortical neurons resistant to amyloid beta protein toxicity, revealing a novel ER-specific apoptosis pathway. She developed a high throughput assay for ER stress and identified salubrinal, a small molecule inhibitor of ER stress-induced cell death, which acts by inhibiting GADD34/PP1 phosphatase complex. Additionally, her research identified necrostatin-1 as an inhibitor of necroptosis, a non-apoptotic cell death pathway, which may serve as a backup mechanism when apoptosis fails. Her findings demonstrate that necroptosis is relevant to neurodegeneration and acute neurological injury, such as ischemic brain injury, where Nec-1 reduces damage with an extended treatment window.

Research topics

• Biology
• Cell biology
• Cancer research
• Biochemistry
• Pathology
• Medicine
• Immunology
• Chemistry
• Neuroscience

Selected publications

• Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target

  Nature Reviews Drug Discovery · 2020 · 475 citations

  Senior authorCorresponding
  DOI

• Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke

  Proceedings of the National Academy of Sciences · 2020 · 160 citations

  Senior authorCorresponding

  deficiency reduces cerebral hemorrhage and delays the onset of neural damage mediated by inflammation. Reduced cerebral perfusion resulting from arterial occlusion promotes the degradation of TAK1, a suppressor of RIPK1, and the transition from necroptosis to apoptosis. Conditional knockout of TAK1 in microglial/infiltrated macrophages and neuronal lineages sensitizes to ischemic infarction by promoting apoptosis. Taken together, our results demonstrate the critical role of necroptosis in mediat…

  DOI

• Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1

  Science · 2023-06-29 · 115 citations

  articleOpen accessCorresponding

  Adenosine monophosphate–activated protein kinase (AMPK) activity is stimulated to promote metabolic adaptation upon energy stress. However, sustained metabolic stress may cause cell death. The mechanisms by which AMPK dictates cell death are not fully understood. We report that metabolic stress promoted receptor-interacting protein kinase 1 (RIPK1) activation mediated by TRAIL receptors, whereas AMPK inhibited RIPK1 by phosphorylation at Ser 415 to suppress energy stress–induced cell death. Inhi…

  PublisherOA PDFDOI

• Prolonged hypoxia alleviates prolyl hydroxylation-mediated suppression of RIPK1 to promote necroptosis and inflammation

  Nature Cell Biology · 2023-07-01 · 59 citations

  articleOpen access
  PublisherOA PDFDOI

• Supplementary Figure 2 from <i>Pten</i> Deficiency Activates Distinct Downstream Signaling Pathways in a Tissue-Specific Manner

  2023-03-30

  preprintOpen accessSenior author

  Supplementary Figure 2 from <i>Pten</i> Deficiency Activates Distinct Downstream Signaling Pathways in a Tissue-Specific Manner

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01GM064703

  NIH · $934k · 2005

• NIH Grant R01CA089434

  NIH · $1.5M · 2006

• NIH Grant DP1OD000580

  NIH · $4.2M · 2012

Frequent coauthors

• Bing Shan

  Shanghai Institute of Organic Chemistry

  128 shared

• Ying Li

  Shanghai Medical College of Fudan University

  98 shared

• Daichao Xu

  Shanghai Institute of Organic Chemistry

  93 shared

• Michael A. Moskowitz

  Harvard University

  91 shared

• Hideaki Hara

  Gifu Pharmaceutical University

  88 shared

• L Bergeron

  McGill University

  70 shared

• Jonathan L. Tilly

  Northeastern University

  70 shared

• Gloria I. Perez

  Michigan State University

  69 shared

Labs

• Junying Yuan LabPI

Education

• Ph.D. Neuroscience

  Harvard University

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• Constance L. Cepkoh-149
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