Department of Cell 240 Longwood Ave. Boston, MA 02115 [email protected] Junying Yuan, Ph.D. Tel: 617 432-4170

Research — Regulation of and by . Interests — Regulation of autophagy.

— The molecular mechanism of , a programmed necrotic pathway.

Professional 2000-present: Professor of Cell Biology ,Harvard Medical School Experience 1997-2000:Associate Professor of Cell Biology,Harvard Medical School

1996-1997:Assistant Professor of Cell Biology,Harvard Medical School.

1992-1996:Assistant Professor of Medicine,Harvard Medical School

1990-1991:Instructor in Medicine,Harvard Medical School Education 1989-1996: Ph.D., — Major: — Director: Prof. H. R. Horvitz, Academician Member of the American Academy of Arts and Sciences, The Nobel Prize winner

1982-1989: B.S., , , China — Major:

Honors and — Fellow of the American Academy of Arts and Sciences (2007) Awards — International Cell Death Society Award in Appreciation of Her Contribution to Research in the Field of Cell Death (2006) — NIH Director’s Pioneer Award (2005) — BBS Mentoring Award, Harvard Medical School(2003) — Merit Award, National Institute of Aging (2002) — Innovator Award for Breast Cancer Research(2002) — SCBA Outstanding Young Investigator Award (1999) — American Heart Established Investigator (1996-1999) — Wilson S. Stone Memorial Award (1994) — Ryan Fellowship(1985-1989)

Professional — Senior Editor of " Journal of Cell Biology " Associations — Reviewing Editor of “Journal of Neuroscience” — Associate Editor of " Genes to Cells " — Executive Editor of “Chinese Science Bulletin”

1 Latest update: 02/10/2009 — Member of the Editorial Board of " Current Biology " — Founding Board member of Rosalind Franklin Society. — number of American Association for Cancer Research — number of Society of Chinese Bioscientists in America — number of American Society for Cell Biology — number of Society for Neuroscience — number of American Society for Biochemistry and Molecular Biology h — number of American Association for Advancement of Science

Original Articles: Selected 1. Yuan J, Horvitz HR. The C. elegans genes ced-3 and ced-4 act cell-autonomou Publications cause programmed cell death. Dev. Biol. 1990; 138:33-41. 2. Yuan J, Finney M, Kim S, Horvitz HR. Tc4, a C. elegans transposon with an unusual foldback structure. Proc. Natl. Acad. Sci. USA 1991; 88:3334-3338 3. Yuan J, Horvitz HR. The C. elegans cell death gene ced-4 encodes a novel protein and is expressed during the period of extensive programmed cell death. Development 1992; 116:309-320 4. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1b converting enzyme. Cell 1993; 75: 641-652. 5. Miura M, Zhu H, Hartwieg EA, Rotello R, Yuan J. Induction of apoptosis in fibroblasts by interleukin-1b converting enzyme, a mammalian homolog of C. elegans cell death gene ced-3. Cell 1993; 75: 653-660 6. Gagliardini V, Fernandez PA, Lee RKK, Drexler HCA, Rotello R, Fishman M, Yuan J. Prevention of vertebrate neuronal death by the crmA gene. Science 1994; 263: 826-828. 7. Rotello R, Fernandez PA, Yuan J. Anti-apogens and anti-engulfens: monoclonal antibodies reveal specific antigens on cells undergoing programmed cell death in developing chick embryos. Development 1994; 120: 1421-1431. 8. Fernandez PA, Rotello R, Rangini Z, Doupe A, Yuan J. Expression of a specific marker of avian programmed cell death in both apoptosis and . Proc. Natl. Acad. Sci. 1994; 91:8641-8645. 9. Wang L, Miura M, Bergeron L, Zhu H, Yuan J. Ich-1, an Ice/Ced-3 related gene, encodes both positive and negative regulators of programmed cell death. Cell 1994; 78:739-750. 10. Miura M, Friedlander RM, Yuan J. TNF-induced apoptosis is mediated by a CrmA-sensitive cell death pathway. Proc. Natl. Acad. Sci. USA PNAS. 1995; 92: 8318-8322. 11. Takashita N, Homma S, Rottello RJ, Fernandez PA, Yuan J, Oppenheim RW,Yaginuma H. Expression of apogens and engulfens during programmed cell death in the nervous system of the chick embryo. Arch Histol Cytol 1995; 58: 243-248 12. Li W, Fishman MC, Yuan J. Prevention of apoptosis in CNTF-dependent neuron a mutated ICE or viral protein CrmA but not by proto-oncogene Bcl-2. Cell Death Differ. 1996; 3:105-112. 13. Jung YK, Miura M, Yuan J. Suppression of interleukin-1b-converting enzyme-m cell death by insulin-like growth factor. J. Biol. Chem. 1996; 271: 5112-5117. 14. Friedlander RM, Gagliardini V, Rotello RJ, Yuan J. Functional role of endogenous IL-1 in apoptosis mediated by the ICE. J. Exp. Med. 1996; 184:717-724. 15. Wang S, Miura M, Jung YK, Zhu H, Gagliardini V, Shi L, Greenberg AH and

2 Latest update: 02/10/2009 Yuan J. Identification and Characterization of ICH-3, a Member of the ICE/Ced-3 Family and an Upstream Regulator of ICE. J. Biol. Chem. 1996; 271: 20580-20587. 16. Shi L, Chen G, Salvesen G, Quan L, Bergeron L, Miura M, Rotello RR, Miller DK, Li P, Seshadri T, Yuan J, Greenberg AH. Activation of an ICE- dependent apoptosis pathway by granzme B. Proc Natl Acad Sci. 1996; 93:11002-11007. 17. Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J. Human ICE/CED-3 protease nomenclature. Cell. 1996; 87: 171. 18. Cryns VL, Bergeron L, Zhu H, Li H, and Yuan J. Specific cleavage of - fodrin during Fas- and TNF-induced apoptosis is mediated by an ICE/Ced-3 family protease distinct from the PARP protease. J Biol Chem. 1996; 271:31277-31282. 19. Jung YK, Yuan J. Induction and suppression of ICE induced apoptosis by oncogenes. Oncogene, 1997; 14:1207-1214. 20. Hara H, Friedlander RM, Gagliardini V, Ayata C, Huang Z, Sasamata M, Yuan J and Moskowitz MA. Inhibition of ICE-Ced-3 family of poteases and ischemic/excitotoxic neuronal damage. Proc Natl Acad Sci U S A 1997; 94:2007-2012. 21. Friedlander RM, Gagliardini V, Hara H, MacDonald G, Greenberg AH, Moskowitz MA, and Yuan J. Inhibition of neuronal apoptosis in a transgenic mouse expressing a dominant negative mutant of ICE. J Exp Med. 1997; 185:933-940. 22. Johnson AL, Bridgham JT, Bergeron L, and Yuan J. Characterization of the avian ich-1 cDNA and expression of ich-1 long mRNA in the hen ovary. Gene. 1997; 192: 227-233. 23. Hara H, Fink K, Endres M, Friedlander RM, Gagliardini V, Yuan J, Moskowitz MA. Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. J Cereb Blood Flow Metab. 1997; 17: 370-375. 24. Friedlander RM, Gagliardini V, Wang J, Brown RH, Yuan J. Inhibition of ICE slows ALS in mice. Nature. 1997; 388: 31. 25. Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L, Greenberg AH and Yuan J. Activation of -2 in apoptosis. J Biol Chem. 1997; 272: 21010-21017. 26. Haviv R, Lindenboim L, Li H, Yuan J, & Stein R. Need for caspases in apoptosis of trophic factor-deprived PC12 cells. J Neurosci Res. 1997; 50: 69- 80. 27. Cryns, VL, Byun Y, Rana A, Mellor| H, Lustig KL, Parker P, Avruch J, Kirschner MW, Yuan J. Specific Proteolysis of the Kinase PRK2 by Caspase- 3 during Apoptosis: Identification by a novel, small pool expression cloning strategy. J Biol Chem. 1997; 272:29449-29453. 28. Zhang Y, Center DM, Wu DMH, Cruikshank WW, Yuan J, Andrews DW, Kornfeld H. Processing and activation of pro-interleukin-16 by caspase-3. J Biol Chem. 1998; 273:1144-1149. 29. Wang S, Miura M, Jung Y-K, Zhu H, Li E, Yuan J. Murine caspase-11, an ICE interacting protease, is essential for the activation of ICE. Cell. 1998; 92:501-509. 30. Bergeron L, Perez GI, MacDonald G, Shi L, Sun Y, Jurisicova| A, Varmuza S, Latham KE, Flaws JA, Salter J, Hara H, Moskowitz MA, Li E, Greenberg A, Tilly JL, Yuan J. Defects in regulation of apoptosis in caspase-2-deficient mice. Genes & Dev. 1998; 12:1304-1314. 31. Weng LP, Yuan J, Yu Q. Overexpression of the transmembrane tyrosine phosphatase LAR activates the caspase pathway and induces apoptosis. Curr Biol. 1998; 8: 247-256. 32. Namura S, Zhu J, Fink K, Endres M, Srinivasan A, Tomaselli KJ, Yuan J,

3 Latest update: 02/10/2009 Moskowitz MA. Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci. 1998; 18: 3659-3668. 33. Zhou BB, Li H, Yuan J, Kirschner MW. Caspase-dependent activation of cyclin-dependent kinases during Fas-induced apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 1998; 95: 6785-6790. 34. Li H, Zhu H, Xu C-J, and Yuan J. Cleavage of BID by mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998; 94:491- 501. 35. Hilbi H, Moss JE, Hersh D, Chen Y, Arondel J, Banerjee S, Flavell RA, Yuan J, Sansonetti PJ, and Zychlinsky A. Shigella-induced apoptosis is dependent on caspase-1 Which binds to IpaB. J Biol Chem. 1998; 273:32895-32900. 36. Haviv R, Lindenboim L, Yuan J, Stein R. Need for caspase-2 in apoptosis of growth-factor-deprived PC12 cells. J Neurosci Res. 1998; 52:491-497. 37. Juo P, Kuo CJ, Yuan J, Blenis J. Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr Biol. 1998; 8:1001-8 38. Fink K, Zhu J, Namura S, Shimizu-Sasamata M, Endres M, Ma J, Dalkara T, Yuan J, Moskowitz MA. Prolonged therapeutic window for ischemic brain damage caused by delayed caspase activation. J Cereb Blood Flow Metab 1998; 18:1071-1076. 39. Chou JJ, Li H, Salveson G, Yuan J and Wagner G. Solution structure of Bid, an intracellular amplifier of apoptosis. Cell. 1999; 96:615-624. 40. Rao VR, Corradetti MN, Chen J, Peng J, Yuan J, Prestwich GD, Brugge JS. Expression cloning of protein targets for 3-phosphorylated phosphoinositides. J Biol Chem. 1999; 274:37893-37900. 41. Sánchez I, Xu CJ, Juo P, Kakizaka A, Blenis J, and Yuan J. Caspase-8 is Required for Cell Death Induced by Expanded Polyglutamine Repeats. Neuron. 1999; 22:623-633. 42. Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ, Chung WM, Frey AS, Menon AS, Li XJ, Stieg PE, Yuan J, Penney JB, Young AB, Cha JH, Friedlander RM. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature. 1999; 399:263-267. 43. Zhou P, Chou J, Olea RS, Yuan J, Wagner G. Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: A structural basis for specific adaptor/caspase interaction. Proc Natl Acad Sci U S A. 2000; 96:11265- 11270. 44. Lindenboim L, Yuan J, Stein R. Bcl-xS and Bax induce different apoptotic pathways in PC12 cells. Oncogene. 2000; 19:1783-1793. 45. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA and Yuan J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid b. Nature. 2000; 403:98-103. 46. Kang SJ, Wang S, Hara H, Peterson EP, Srinivasan A, Namura S, Amin- Hanjani S, Tomaselli K J, Thornberry NJ, Moskowitz MA and Yuan J. Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions. J Cell Biol. 2000; 149:613-622. 47. Nakagawa T and Yuan J. Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis. J Cell Biol. 2000; 150:887- 894. 48. Ruffolo SC, Breckenridge DG, Nguyen M, Goping IS, Gross A, Korsmeyer SJ, Li H, Yuan J, Shore GC. BID-dependent and BID-independent pathways for BAX insertion into mitochondria. Cell Death Differ. 2000; 7:1101-1108. 49. Jesenberger V, Procyk KJ, Yuan J, Reipert S, Baccarini M. Salmonella- induced caspase-2 activation in macrophages: a novel mechanism in pathogen-mediated apoptosis. J Exp Med. 2000; 192:1035-1046. 50. Matsushita K, Wu Y, Qiu J, Lang-Lazdunski L, Hirt L, Waeber C, Hyman BT,

4 Latest update: 02/10/2009 Yuan J, Moskowitz MA. and neuronal cell death after spinal cord ischemia. J Neurosci. 2000; 20:6879-6887. 51. Ding HF, Lin YL, McGill G, Juo P, Zhu H, Blenis J, Yuan J, Fisher DE. Essential role for caspase-8 in transcription-independent apoptosis triggered by p53. J Biol Chem. 2000; 275:38905-38911. 52. Degterev A, Lugovskoy, Cardone M, Mulley B, Wagner G, Mitchison T and Yuan J. Identification of small molecular inhibitors of BH3 and Bcl-xL interaction. Nat Cell Biol. 2001; 3:173-182. 53. Kim KW, Chung HH, Chung CW, Kim IK, Miura M, Wang S, Zhu H, Moon KD, Rha GB, Park JH, Jo DG, Woo HN, Song YH, Kim BJ, Yuan J, Jung YK. Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: Cleavage of the common alpha subunit during apoptosis. Oncogene. 2001; 20:358-366. 54. Hisahara S, Yuan J, Momoi T, Okano H, Miura M. Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination. J Exp Med. 2001; 193:111-122. 55. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, Brien TP, Bozzuto CD, Ooi D, Cantley LC, and Yuan J. The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Molecular Cell. 2001; 7:1307-1319 56. Morita Y, Maravei DV, Bergeron L, Wang S, Perez GI, Tsutsumi O, Taketani Y, Asano M, Horai R, Korsmeyer SJ, Iwakura Y, Yuan J, Tilly JL. Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia- mutated (Atm) gene function. Cell Death Differ. 2001; 8:614-620. 57. Lugovskoy AA, Degterev AI, Fahmy AF, Zhou P, Gross JD, Yuan J, Wagner G. A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors. J Am Chem Soc. 2002; 124:1234-1240. 58. Qiu J, Whalen MJ, Lowenstein P, Fiskum G, Fahy B, Darwish R, Aarabi B, Yuan J, Moskowitz MA. Upregulation of the Fas receptor death-inducing signaling complex after traumatic brain injury in mice and humans. J Neurosci. 2002; 22:3504-3511. 59. Garden GA, Budd SL, Tsai E, Hanson L, Kaul M, D'Emilia DM, Friedlander RM, Yuan J, Masliah E, Lipton SA. Caspase cascades in human immunodeficiency virus-associated neurodegeneration. J Neurosci. 2002; 22:4015-4024. 60. Le DA, Wu Y, Huang Z, Matsushita K, Plesnila N, Augustinack JC, Hyman BT, Yuan J, Kuida K, Flavell RA, Moskowitz MA. Caspase activation and neuroprotection in caspase-3-deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation.Proc Natl Acad Sci U S A. 2002; 99:15188-15193. 61. Kang SJ, Wang S, Kuida K, Yuan J. Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response. Cell Death Differ. 2002; 9:1115-1125. 62. Sanchez I, Mahlke C, Yuan J. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature. 2003; 421:373-379. 63. Kang SJ, Sanchez I, Jing N, Yuan J. Dissociation between Neurodegeneration and Caspase-11-mediated Activation of Caspase-1 and – 3 in a Mouse Model of ALS. J Neurosci. 2003; 23:5455-5460. 64. Zong WX, Li C, Hatzivassiliou G, Lindsten T, Yu QC, Yuan J, Thompson CB.

5 Latest update: 02/10/2009 Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol. 2003; 162:59-69. 65. Takai Y, Canning J, Perez GI, Pru JK, Schlezinger JJ, Sherr DH, Kolesnick RN, Yuan J, Flavell RA, Korsmeyer SJ, Tilly JL. Bax, caspase-2, and caspase-3 are required for ovarian follicle loss caused by 4-vinylcyclohexene diepoxide exposure of female mice in vivo. Endocrinology. 2003; 144:69-74. 66. Gozani O, Karuman P,Jones DR, Ivanov D, Cha J, Lugovskoy AA, Baird CL, Zhu H, Field SJ, Lessnic, SL, Villasenor J, Mehrotra B, Chen J, Rao VR, Brugge JS, Gerguson CG, Payrasre B, Myska DG, Cantley LC, Wagner G, Divecha N, Prestwich GD and Yuan J. The PHD finger of the chromatin- associated protein ING2 functions as a nuclear phosphoinositide receptor. Cell. 2003; 114:99-111. 67. Kobori M, Yabg Z, Gong D, Heissmeyer V, Zhu H, Jung Y-K, Angelica Gakidis M, Rao A, Sekine T, Ikegam F, Yuan C, and Yuan J. Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex. Cell Death & Differ. 2004; 11:123-130. 68. Terui Y, Saad N, Jia S, McKeon F, Yuan J. Dual role of sumoylation in the nuclear localization and transcriptional activation of NFAT1. J Biol Chem. 2004; 279:28257-28265 69. Qiu XB, Markant SL, Yuan J, Goldberg AL. Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis. EMBO J. 2004; 23:800-810. 70. Gozani O, Field SJ, Ferguson CG, Ewalt M, Mahlke C, Cantley LC, Prestwich GD, Yuan J. Modification of protein sub-nuclear localization by synthetic phosphoinositides: evidence for nuclear phosphoinositide signaling mechanisms. Adv Enzyme Regul. 2005; 45:171-185 71. Teng X, Degterev A, Jagtap P, Xing X, Choi S, Denu R, Yuan J, Cuny GD. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett. 2005; 15:5039-5044 72. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D and Yuan J. A Selective Inhibitor of eIF2 Dephosphorylation Protects Cells from ER Stress. Science. 2005; 307:935-939. 73. Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA and Yuan J. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005; 1:112-119. 74. Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner, B and Yuan J. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J Biol Chem. 2006; 281:14474-14485. 75. Yoo L.I, Liu DW, Le Vu S, Bronson RT, Wu H, and Yuan J. Pten deficiency activates distinct downstream signaling pathways in a tissue-specific manner. Cancer Res. 2006; 66:1929-1939. 76. Zhang Y, Zhou X, Degterev A, Lipinski M, Adjeroh D, Yuan J, Wong ST. A novel tracing algorithm for high throughput imaging Screening of neuron- based assays. J Neurosci Methods. 2006; 160:149-162. 77. Wang K, Li J, Degterev A, Hsu E, Yuan J and Yuan C. Structure activity relationship analysis of a novel necroptsis inhibitor, Necrostatin-5. Bioorg & Med Chem Lett. 2006; 17:1455-1465. 78. Matsui T, Ramasamy K, Ingelsson M, Fukumoto H, Conrad C, Frosch MP, Irizarry MC, Yuan J, Hyman BT. Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: relationship to formic acid extractable abeta42 levels. J Neuropathol Exp Neurol. 2006; 65:508-515.

6 Latest update: 02/10/2009 79. Li J, Brieher WM, Scimone ML, Zhu H, Yin H, von Andrian U, Mitchison T and Yuan J. Caspase-11 regulates cell migration by promoting Aip1/Cofilin mediated actin depolymerization. Nat Cell Biol. 2007; 9:276-286. 80. Jagtap PG, Degterev A, Choi S, Keys H, Yuan J, Cuny GD. Structure-Activity Relationship Study of Tricyclic Necroptosis Inhibitors. J Med Chem. 2007; 50:1886-1895. 81. Wang K, Li J, Degterev A, Hsu E, Yuan J, Yuan C. Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5. Bioorg Med Chem Lett. 2007; 17:1455-1465. 82. Py BF, Lipinski MM, Yuan J. Autophagy limits Listeria monocytogenes intracellular growth in the early phase of primary infection. Autophagy. 2007; 3:117-125. 83. 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; 128:257-267. 84. Zhang Y, Zhou X, Degterev A, Lipinski M, Adjeroh D, Yuan J, Wong ST. Automated neurite extraction using dynamic programming for high-throughput screening of neuron-based assays. Neuroimage. 2007; 35:1502-1515. 85. Takai Y, Matikainen T, Jurisicova A, Kim MR, Trbovich AM, Fujita E, Nakagawa T, Lemmers B, Flavell RA, Hakem R, Momoi T, Yuan J, Tilly JL, Perez GI. Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Apoptosis. 2007; 12:791-800. 86. 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; 179:619-626. 87. 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; 104:19023-19028. 88. 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; 28:914-922. 89. Boyce M, Py BF, Ryazanov AG, Minden JS, Long K, Ma D, Yuan J. A pharmacoproteomic approach implicates eukaryotic elongation factor 2 kinase in ER stress-induced cell death. Cell Death Differ. 2008; 15:589-99. 90. 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. 91. Degterev A, Hitomi J, Germscheid JM, Ch’en I, 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; 4:313-321. 92. Li J, Yin H & Yuan J. Regulation of pro-inflammatory caspases by Flightless-I. J Cell Biol. 2008; 181:321-333. 93. 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 USA. 2008; 105:6584-6589. 94. 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: 3219-3223. 95. 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; 283:24400-24405. 96. You Z, Savitz SI, Yang J, Degterev A, Yuan J, Cuny GD, Moskowitz MA,

7 Latest update: 02/10/2009 Whalen MJ. Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice. J Cereb Blood Flow Metab. 2008; 28:1564-1573. 97. 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. 98. 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 ARF and golgi membrane trafficking. J Biol Chem. 2008. 283, 24400-5 99. Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavior RJ and Yuan J. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 2008. 135, 1311-23. 100. Shen S, Zhang P, Lovchik MA, Li Y, Tang L, Chen Z, Zeng R, Ma D, Yuan J and Yu Q. Cyclodepsipeptide toxin promotes the degradation of Hsp90 client proteins through chaperone-mediated autophagy. J Cell Biol. 2009. In press

Reviews, Chapters and Editorials: 1. Ellis R, Yuan J, Horvitz HR. Mechanisms and functions of cell death. Ann. Rev. Cell. Biol. 1991; 7:663-698\ 2. Yuan, J. Molecular Control of life and death. Cur Opin Cell Biol. 1995; 7:211-214. 3. Yuan, J. The genes that regulate programmed cell death: from worm to mammal. Proceedings of Princeton Conference. 1995. In: Cerebrovascular Diseases. Nineteenth Princeton Conference. M. A. Moskowitz and L. R. Caplan (eds). Butterworth-Heinemann, Boston, MA. pp199-218. 4. Miura M, Yuan J. Mechanisms of programmed cell death in C. elegans and vertebrates. Curr Topics Dev. Biol. 1996; 32: pp.139-174. 5. Yuan, J. Evolutionary conservation of a genetic pathway of programmed cell death. J Cellu Biochem. 1996; 60:4-11 6. Drexler HCA, Yuan J. Control of cell death in the nervous system. In: Apoptosis in Normal Development and Cancer. M. Sluyser, ed. Taylor and Francis, Inc. 1996; pp.277-298. 7. Yuan J. 1997. Genetic control of cellular suicide. Reprod. Toxicology.11/2- 3:377-384. 8. Yuan J. Transducing signals of life and death. Curr Opin Cell Biol 1997; 9: 247-251. 9. Lustig KD, Stukenberg PT, McGarry TJ, King RW, Cryns VL, Mead PE, Zon LI, Yuan J, and Kirschner MW. Small pool expression screening: a novel strategy for the identification of genes involved in cell cycle control, apoptosis and early development. Meths of Enz. 1997; 283:83-99. 10. Cryns VL and Yuan J. The cutting edge: ICE/CED-3 proteases in apoptosis and disease. In: Lockshin RA, Zakeri Z, and Tilly L, eds. 1998. Why Cells Die: A Comprehensive Evaluation of Apoptosis and Programmed Cell Death. 11. Bergeron L, & Yuan J. Sealing one’s fate: control of neuronal cell death. Curr Opin Neurobiol. 1998; 8:55-63. 12. Cryns VL and Yuan J. Proteases to die for. Gen. & Dev. 1998; 12:1551- 1570. 13. Li H & Yuan J. Deciphering the Pathways of Life and Death. Curr Opin Cell Biol. 1999; 11: 261-266. 14. Yuan J & Yankner B. Seeds of death: Caspase Cleavage and the Generation of Toxic Protein Fragments in Alzheimer’s and Huntington’s Diseases. News & Views. Nat Cell Biol. 1999. 1, E44- E45. 15. Degterev A and Yuan J. A new savior for neurons. News & Views. Nat Neurosci. 1999; 2:930-932 16. Yuan J and Yankner B. Apoptosis in Nervous System. Nature (Insight).

8 Latest update: 02/10/2009 2000; 407:802-809. 17. Sanchez I and Yuan J. A convoluted way to die. Neuron. 2001; 29:563-566. 18. Degterev A, Boyce M, Yuan J. The channel of death. J Cell Biol. 2001; 155:695-8. 19. Welch K, Yuan J. Releasing the nerve cell killers. Nat Med. 2002; 8:564-5. 20. Gozani O, Boyce M, Yoo L, Karuman P, Yuan J. Life and death in paradise. Nat Cell Biol. 2002; 4:E159-62. 21. Yoo LI, Chung DC, Yuan J. LKB1--a master tumour suppressor of the small intestine and beyond. Nat Rev Cancer. 2002; 2:529-535. 22. Yuan J and Morgan D. (eds). Cell division, growth and death. Curr Opin Cell Biol. 2002; 14:6. 23. Yuan J, Lipinski M, Degterev A. Diversity in the mechanisms of neuronal cell death.Neuron. 2003; 40:401-413. 24. Welch K, Yuan J. Alpha-synuclein oligomerization: a role for lipids? Trends Neurosci. 2003; 26:517-519. 25. Degterev A, Boyce M, Yuan J. A decade of caspases. Oncogene. 2003; 22:8543-8567. 26. Boyce M, Degterev A, and Yuan J. Caspases: an ancient cellular sword of Damocles. Cell Death and Differ. 2004; 11:29-37. 27. Yuan J and Horvitz HR. A first insight into the molecular mechanisms of apoptosis. Cell. 2004; S116:S53-S56. 28. Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest. 2005; 115:2679-2688. 29. Lipinski MM, Yuan J. A cellular response to an internal energy crisis. Cell. 2005; 123:3-5. 30. Boyce M, Yuan J. Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ. 2006; 13:363-373. 31. Yuan J. (ed). Special Issue on ER stress. Cell Death Differ. 2006; 13. 32. Yuan, J. Divergence from a dedicated cellular suicide mechanism: exploring the evolution of cell death. Mol Cell. 2006; 23:1-12. 33. Yuan J. Inducing autophagy harmlessly. Autophagy. 2008. 4, 249-50. 34. Degterev A & Yuan J. Expansion and Evolution of Cell Death Programs. Nat Rev Mol Biol. 2008; 9:378-390. 35. Li J & Yuan J. Caspases in apoptosis and beyond. Oncogene. 2008. 27, 6194-206.

9 Latest update: 02/10/2009