Photo of Junying Yuan,  PhD

Junying Yuan, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-4170
Fax: (617) 432-4177


junying_yuan@hms.harvard.edu

Junying Yuan, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Elizabeth D. Hay Professor of Cell Biology, Cell Biology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Yuan lab is studying the signal transduction mechanism of apoptosis. We focus on the roles of caspase family in regulating apoptosis. Disregulation of apoptosis plays an important role in cancer development. We would like to understand the interaction of tumor promoting genes with apoptosis mechinary and how defects in apoptosis regulation lead to cancer development.

Publications

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  • Najjar M, Suebsuwong C, Ray SS, Thapa RJ, Maki JL, Nogusa S, Shah S, Saleh D, Gough PJ, Bertin J, Yuan J, Balachandran S, Cuny GD, Degterev A. Structure guided design of potent and selective ponatinib-based hybrid inhibitors for RIPK1. Cell Rep 2015. PubMed
  • Xiao J, Zhang T, Xu D, Wang H, Cai Y, Jin T, Liu M, Jin M, Wu K, Yuan J. FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation. Genes Dev 2015; 29:184-96. PubMed
  • Vakifahmetoglu-Norberg H, Xia HG, Yuan J. Pharmacologic agents targeting autophagy. J Clin Invest 2015; 125:5-13. PubMed
  • Zhou W, Yuan J. Necroptosis in health and diseases. Semin Cell Dev Biol 2014; 35C:14-23. PubMed
  • Zhou W, Yuan J. SnapShot: Necroptosis. Cell 2014; 158:464-464.e1. PubMed
  • Py BF, Jin M, Desai BN, Penumaka A, Zhu H, Kober M, Dietrich A, Lipinski MM, Henry T, Clapham DE, Yuan J. Caspase-11 controls interleukin-1β release through degradation of TRPC1. Cell Rep 2014; 6:1122-8. PubMed
  • Christofferson DE, Li Y, Yuan J. Control of life-or-death decisions by RIP1 kinase. Annu Rev Physiol 2014; 76:129-50. PubMed
  • Vakifahmetoglu-Norberg H, Yuan J. A degradative detour for mutant TP53. Autophagy 2013; 9:2158-60. PubMed
  • Xu Y, Yuan J, Lipinski MM. Live imaging and single-cell analysis reveal differential dynamics of autophagy and apoptosis. Autophagy 2013; 9:1418-30. PubMed
  • Vakifahmetoglu-Norberg H, Kim M, Xia HG, Iwanicki MP, Ofengeim D, Coloff JL, Pan L, Ince TA, Kroemer G, Brugge JS, Yuan J. Chaperone-mediated autophagy degrades mutant p53. Genes Dev 2013; 27:1718-30. PubMed
  • Choi S, Keys H, Staples RJ, Yuan J, Degterev A, Cuny GD. Optimization of tricyclic Nec-3 necroptosis inhibitors for in vitro liver microsomal stability. Bioorg Med Chem Lett 2012; 22:5685-8. PubMed
  • Gu Y, Qi C, Sun X, Ma X, Zhang H, Hu L, Yuan J, Yu Q. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism. Biochem Pharmacol 2012; 84:468-76. PubMed
  • Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee JH, Loh YH, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LS, Zhang K. Somatic coding mutations in human induced pluripotent stem cells. Nature 2011; 471:63-7. PubMed
  • Kepp O, Galluzzi L, Lipinski M, Yuan J, Kroemer G. Cell death assays for drug discovery. Nat Rev Drug Discov 2011; 10:221-37. PubMed
  • Miao B, Skidan I, Yang J, Lugovskoy A, Reibarkh M, Long K, Brazell T, Durugkar KA, Maki J, Ramana CV, Schaffhausen B, Wagner G, Torchilin V, Yuan J, Degterev A. Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains. Proc Natl Acad Sci U S A 2010; 107:20126-31. PubMed
  • Huang Y, Zhou X, Miao B, Lipinski M, Zhang Y, Li F, Degterev A, Yuan J, Hu G, Wong ST. A Computational Framework for Studying Neuron Morphology from in vitro High Content Neuron-based Screening. J Neurosci Methods 2010; 190:299-309. PubMed
  • Lipinski MM, Hoffman G, Ng A, Zhou W, Py BF, Hsu E, Liu X, Eisenberg J, Liu J, Blenis J, Xavier RJ, Yuan J. A genome-wide siRNA screen reveals multiple mTORC1 independent signaling pathways regulating autophagy under normal nutritional conditions. Dev Cell 2010; 18:1041-52. PubMed
  • Furuya T, Kim M, Lipinski M, Li J, Kim D, Lu T, Shen Y, Rameh L, Yankner B, Tsai LH, Yuan J. Negative regulation of Vps34 by Cdk mediated phosphorylation. Mol Cell 2010; 38:500-11. PubMed
  • Rosenbaum DM, Degterev A, David J, Rosenbaum PS, Roth S, Grotta JC, Cuny GD, Yuan J, Savitz SI. Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model. J Neurosci Res 2010; 88:1569-76. PubMed
  • Christofferson DE, Yuan J. Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol 2010; 22:263-8. PubMed
  • Xia HG, Zhang L, Chen G, Zhang T, Liu J, Jin M, Ma X, Ma D, Yuan J. Control of basal autophagy by calpain1 mediated cleavage of ATG5. Autophagy 2010; 6:61-6. PubMed
  • Shen S,Zhang P,Lovchik MA,Li Y,Tang L,Chen Z,Zeng R,Ma D,Yuan J,Yu Q. Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy. J Cell Biol 2009; 185:629-39. PubMed
  • Py BF,Boyce M,Yuan J. A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses. Autophagy 2009; 5:393-6. PubMed
  • Yuan J. Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis 2009; 14:469-77. PubMed
  • Panaretakis T,Kepp O,Brockmeier U,Tesniere A,Bjorklund AC,Chapman DC,Durchschlag M,Joza N,Pierron G,van Endert P,Yuan J,Zitvogel L,Madeo F,Williams DB,Kroemer G. Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. EMBO J 2009; 28:578-90. PubMed
  • Yi CH,Yuan J. The Jekyll and Hyde functions of caspases. Dev Cell 2009; 16:21-34. PubMed
  • Hitomi J,Christofferson DE,Ng A,Yao J,Degterev A,Xavier RJ,Yuan J. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 2008; 135:1311-23. PubMed
  • Ch'en IL,Beisner DR,Degterev A,Lynch C,Yuan J,Hoffmann A,Hedrick SM. Antigen-mediated T cell expansion regulated by parallel pathways of death. Proc Natl Acad Sci U S A 2008; 105:17463-8. PubMed
  • Pan H,Yu J,Zhang L,Carpenter A,Zhu H,Li L,Ma D,Yuan J. A novel small molecule regulator of guanine nucleotide exchange activity of the ADP-ribosylation factor and golgi membrane trafficking. J Biol Chem 2008; 283:31087-96. PubMed
  • Bryant KF,Macari ER,Malik N,Boyce M,Yuan J,Coen DM. ICP34.5-dependent and -independent activities of salubrinal in herpes simplex virus-1 infected cells. Virology 2008; 379:197-204. PubMed
  • Zheng W,Degterev A,Hsu E,Yuan J,Yuan C. Structure-activity relationship study of a novel necroptosis inhibitor, necrostatin-7. Bioorg Med Chem Lett 2008; 18:4932-5. PubMed
  • Sanchez-Olea R,Ortiz S,Barreto O,Yang Q,Xu CJ,Zhu H,Yuan J. Parcs is a dual regulator of cell proliferation and apaf-1 function. J Biol Chem 2008; 283:24400-5. PubMed
  • You Z,Savitz SI,Yang J,Degterev A,Yuan J,Cuny GD,Moskowitz MA,Whalen MJ. Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice. J Cereb Blood Flow Metab 2008; 28:1564-73. PubMed
  • Teng X, Keys H, Yuan J, Degterev A, Cuny GD. Structure-activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors. Bioorg Med Chem Lett 2008; 18:3219-23. PubMed
  • Zhu J, Blenis J, Yuan J. Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc Natl Acad Sci U S A 2008; 105:6584-9. PubMed
  • Degterev A, Yuan J. Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol 2008; 9:378-90. PubMed
  • Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 2008; 4:313-21. PubMed
  • Oh YK, Shin KS, Yuan J, Kang SJ. Superoxide dismutase 1 mutants related to amyotrophic lateral sclerosis induce endoplasmic stress in neuro2a cells. J Neurochem 2008; 104:993-1005. PubMed
  • Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 2008; 27:433-46. PubMed
  • Teng X, Keys H, Jeevanandam A, Porco JA Jr, Degterev A, Yuan J, Cuny GD. Structure-activity relationship study of [1,2,3]thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett 2007; 17:6836-40. PubMed
  • Xu L, Zhu J, Hu X, Zhu H, Kim HT, LaBaer J, Goldberg A, Yuan J. c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Mol Cell 2007; 28:914-22. PubMed
  • Sanchez-Olea R, Yuan J. To kill or to arrest: that is the new question for Apaf-1. Mol Cell 2007; 28:520-1. PubMed
  • Zhang L, Yu J, Pan H, Hu P, Hao Y, Cai W, Zhu H, Yu AD, Xie X, Ma D, Yuan J. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci U S A 2007; 104:19023-8. PubMed
  • Yi CH, Sogah DK, Boyce M, Degterev A, Christofferson DE, Yuan J. A genome-wide RNAi screen reveals multiple regulators of caspase activation. J Cell Biol 2007; 179:619-26. PubMed
  • Platoshyn O, Yu Y, Ko EA, Remillard CV, Yuan JX. Heterogeneity of hypoxia-mediated decrease in IK(V) and increase in [Ca2+]cyt in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2007; 293:L402-16. PubMed
  • Worley PF, Zeng W, Huang GN, Yuan JP, Kim JY, Lee MG, Muallem S. TRPC channels as STIM1-regulated store-operated channels. Cell Calcium 2007; 42:205-11. PubMed
  • Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S. STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat Cell Biol 2007; 9:636-45. PubMed
  • Wu H, Wang X, Liu S, Wu Y, Zhao T, Chen X, Zhu L, Wu Y, Ding X, Peng X, Yuan J, Wang X, Fan W, Fan M. Sema4C participates in myogenic differentiation in vivo and in vitro through the p38 MAPK pathway. Eur J Cell Biol 2007; 86:331-44. PubMed
  • Gu G, Yuan J, Wills M, Kasper S. Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo. Cancer Res 2007; 67:4807-15. PubMed
  • Tillman JE, Yuan J, Gu G, Fazli L, Ghosh R, Flynt AS, Gleave M, Rennie PS, Kasper S. DJ-1 Binds Androgen Receptor Directly and Mediates Its Activity in Hormonally Treated Prostate Cancer Cells. Cancer Res 2007; 67:4630-7. PubMed
  • Guo SY, Shen X, Yang J, Yuan J, Yang RL, Mao K, Zhao DH, Li CJ. TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner. Braz J Med Biol Res 2007; 40:621-31. PubMed
  • Wang ZH, Gao L, Li YY, Zhang Z, Yuan JM, Wang HW, Zhang L, Zhu L. Induction of apoptosis by buckwheat trypsin inhibitor in chronic myeloid leukemia K562 cells. Biol Pharm Bull 2007; 30:783-6. PubMed
  • Yuan J, Sun N, Wang LJ, Tian W, Zhou XM, Chen DB, Gu HB. [Radiosensitivity of nasopharyngeal carcinoma in relation to cell cycle synchronization effect of tumor necrosis factor alpha] Nan Fang Yi Ke Da Xue Xue Bao 2007; 27:374-6. PubMed
  • Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, Gross JD, Degterev A, Yuan J, Chorev M, Halperin JA, Wagner G. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 2007; 128:257-67. PubMed
  • Stegh AH, Kim H, Bachoo RM, Forloney KL, Zhang J, Schulze H, Park K, Hannon GJ, Yuan J, Louis DN, DePinho RA, Chin L. Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. Genes Dev 2007; 21:98-111. PubMed
  • Sp. Down-regulation of Polo-like kinase 1 elevates drug sensitivity of breast cancer cells in vitro and in vivo. Cancer Res 2006; 66:5836-46. PubMed
  • Yoo LI, Liu DW, Le Vu S, Bronson RT, Wu H, Yuan J. Pten deficiency activates distinct downstream signaling pathways in a tissue-specific manner. Cancer Res 2006; 66:1929-39. PubMed
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