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127


Bacteria, it's What's for Dinner

Cadwell, Ken
While intestinal epithelial cells are known for secreting antimicrobial molecules, cell intrinsic defense mechanisms are less characterized. In this issue, Benjamin et al. (2013) demonstrate that MyD88 and autophagy within the intestinal epithelium detect invasive bacteria and prevent dissemination.
PMCID:3034397
PMID: 23768486
ISSN: 1931-3128
CID: 394132

FIP200 regulates targeting of Atg16L1 to the isolation membrane

Nishimura, Taki; Kaizuka, Takeshi; Cadwell, Ken; Sahani, Mayurbhai H; Saitoh, Tatsuya; Akira, Shizuo; Virgin, Herbert W; Mizushima, Noboru
Autophagosome formation is a dynamic process that is strictly controlled by autophagy-related (Atg) proteins. However, how these Atg proteins are recruited to the autophagosome formation site or autophagic membranes remains poorly understood. Here, we found that FIP200, which is involved in proximal events, directly interacts with Atg16L1, one of the downstream Atg factors, in an Atg14- and phosphatidylinositol 3-kinase-independent manner. Atg16L1 deletion mutants, which lack the FIP200-interacting domain, are defective in proper membrane targeting. Thus, FIP200 regulates not only early events but also late events of autophagosome formation through direct interaction with Atg16L1.
PMCID:3589088
PMID: 23392225
ISSN: 1469-221x
CID: 232302

Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo

Wang, Caihong; Mendonsa, Graziella R; Symington, Jane W; Zhang, Qunyuan; Cadwell, Ken; Virgin, Herbert W; Mysorekar, Indira U
Urinary tract infection (UTI), a frequent and important disease in humans, is primarily caused by uropathogenic Escherichia coli (UPEC). UPEC forms acute cytoplasmic biofilms within superficial urothelial cells and can persist by establishing membrane-enclosed latent reservoirs to seed recurrent UTI. The host responds with an influx of innate immune cells and shedding of infected epithelial cells. The autophagy gene ATG16L1 has a commonly occurring mutation that is associated with inflammatory disease and intestinal cell abnormalities in mice and humans. Here, we show that Atg16L1-deficient mice (Atg16L1(HM)) cleared bacteriuria more rapidly and thoroughly than controls and showed rapid epithelial recovery. Atg16L1 deficiency was associated with a potent proinflammatory cytokine response with increased recruitment of monocytes and neutrophils to infected bladders. Chimeric and genetic studies showed that Atg16L1(HM) hematopoietic cells alone could increase clearance and that Atg16L1-deficient innate immune cells were required and sufficient for enhanced bacteriuric clearance. We also show that Atg16L1-deficient mice exhibit cell-autonomous architectural aberrations of superficial urothelial cells, including increases in multivesicular bodies, lysosomes, and expression of the UPEC receptor Up1a. Finally, we show that Atg16L1(HM) epithelial cells contained a significantly reduced number of latent reservoirs. Together, our results show that Atg16L1 deficiency confers protection in vivo to the host against both acute and latent UPEC infection, suggest that deficiency in a key autophagy protein can be protective against infection in an animal model of one of the most common diseases of women worldwide, and may have significant clinical implications for understanding the etiology of recurrent UTIs.
PMCID:3390880
PMID: 22715292
ISSN: 0027-8424
CID: 232312

Guidelines for the use and interpretation of assays for monitoring autophagy [Guideline]

Klionsky, Daniel J; Abdalla, Fabio C; Abeliovich, Hagai; Abraham, Robert T; Acevedo-Arozena, Abraham; Adeli, Khosrow; Agholme, Lotta; Agnello, Maria; Agostinis, Patrizia; Aguirre-Ghiso, Julio A; Ahn, Hyung Jun; Ait-Mohamed, Ouardia; Ait-Si-Ali, Slimane; Akematsu, Takahiko; Akira, Shizuo; Al-Younes, Hesham M; Al-Zeer, Munir A; Albert, Matthew L; Albin, Roger L; Alegre-Abarrategui, Javier; Aleo, Maria Francesca; Alirezaei, Mehrdad; Almasan, Alexandru; Almonte-Becerril, Maylin; Amano, Atsuo; Amaravadi, Ravi; Amarnath, Shoba; Amer, Amal O; Andrieu-Abadie, Nathalie; Anantharam, Vellareddy; Ann, David K; Anoopkumar-Dukie, Shailendra; Aoki, Hiroshi; Apostolova, Nadezda; Arancia, Giuseppe; Aris, John P; Asanuma, Katsuhiko; Asare, Nana Y O; Ashida, Hisashi; Askanas, Valerie; Askew, David S; Auberger, Patrick; Baba, Misuzu; Backues, Steven K; Baehrecke, Eric H; Bahr, Ben A; Bai, Xue-Yuan; Bailly, Yannick; Baiocchi, Robert; Baldini, Giulia; Balduini, Walter; Ballabio, Andrea; Bamber, Bruce A; Bampton, Edward T W; Banhegyi, Gabor; Bartholomew, Clinton R; Bassham, Diane C; Bast, Robert C Jr; Batoko, Henri; Bay, Boon-Huat; Beau, Isabelle; Bechet, Daniel M; Begley, Thomas J; Behl, Christian; Behrends, Christian; Bekri, Soumeya; Bellaire, Bryan; Bendall, Linda J; Benetti, Luca; Berliocchi, Laura; Bernardi, Henri; Bernassola, Francesca; Besteiro, Sebastien; Bhatia-Kissova, Ingrid; Bi, Xiaoning; Biard-Piechaczyk, Martine; Blum, Janice S; Boise, Lawrence H; Bonaldo, Paolo; Boone, David L; Bornhauser, Beat C; Bortoluci, Karina R; Bossis, Ioannis; Bost, Frederic; Bourquin, Jean-Pierre; Boya, Patricia; Boyer-Guittaut, Michael; Bozhkov, Peter V; Brady, Nathan R; Brancolini, Claudio; Brech, Andreas; Brenman, Jay E; Brennand, Ana; Bresnick, Emery H; Brest, Patrick; Bridges, Dave; Bristol, Molly L; Brookes, Paul S; Brown, Eric J; Brumell, John H; Brunetti-Pierri, Nicola; Brunk, Ulf T; Bulman, Dennis E; Bultman, Scott J; Bultynck, Geert; Burbulla, Lena F; Bursch, Wilfried; Butchar, Jonathan P; Buzgariu, Wanda; Bydlowski, Sergio P; Cadwell, Ken; Cahova, Monika; Cai, Dongsheng; Cai, Jiyang; Cai, Qian; Calabretta, Bruno; Calvo-Garrido, Javier; Camougrand, Nadine; Campanella, Michelangelo; Campos-Salinas, Jenny; Candi, Eleonora; Cao, Lizhi; Caplan, Allan B; Carding, Simon R; Cardoso, Sandra M; Carew, Jennifer S; Carlin, Cathleen R; Carmignac, Virginie; Carneiro, Leticia A M; Carra, Serena; Caruso, Rosario A; Casari, Giorgio; Casas, Caty; Castino, Roberta; Cebollero, Eduardo; Cecconi, Francesco; Celli, Jean; Chaachouay, Hassan; Chae, Han-Jung; Chai, Chee-Yin; Chan, David C; Chan, Edmond Y; Chang, Raymond Chuen-Chung; Che, Chi-Ming; Chen, Ching-Chow; Chen, Guang-Chao; Chen, Guo-Qiang; Chen, Min; Chen, Quan; Chen, Steve S-L; Chen, WenLi; Chen, Xi; Chen, Xiangmei; Chen, Xiequn; Chen, Ye-Guang; Chen, Yingyu; Chen, Yongqiang; Chen, Yu-Jen; Chen, Zhixiang; Cheng, Alan; Cheng, Christopher H K; Cheng, Yan; Cheong, Heesun; Cheong, Jae-Ho; Cherry, Sara; Chess-Williams, Russ; Cheung, Zelda H; Chevet, Eric; Chiang, Hui-Ling; Chiarelli, Roberto; Chiba, Tomoki; Chin, Lih-Shen; Chiou, Shih-Hwa; Chisari, Francis V; Cho, Chi Hin; Cho, Dong-Hyung; Choi, Augustine M K; Choi, DooSeok; Choi, Kyeong Sook; Choi, Mary E; Chouaib, Salem; Choubey, Divaker; Choubey, Vinay; Chu, Charleen T; Chuang, Tsung-Hsien; Chueh, Sheau-Huei; Chun, Taehoon; Chwae, Yong-Joon; Chye, Mee-Len; Ciarcia, Roberto; Ciriolo, Maria R; Clague, Michael J; Clark, Robert S B; Clarke, Peter G H; Clarke, Robert; Codogno, Patrice; Coller, Hilary A; Colombo, Maria I; Comincini, Sergio; Condello, Maria; Condorelli, Fabrizio; Cookson, Mark R; Coombs, Graham H; Coppens, Isabelle; Corbalan, Ramon; Cossart, Pascale; Costelli, Paola; Costes, Safia; Coto-Montes, Ana; Couve, Eduardo; Coxon, Fraser P; Cregg, James M; Crespo, Jose L; Cronje, Marianne J; Cuervo, Ana Maria; Cullen, Joseph J; Czaja, Mark J; D'Amelio, Marcello; Darfeuille-Michaud, Arlette; Davids, Lester M; Davies, Faith E; De Felici, Massimo; de Groot, John F; de Haan, Cornelis A M; De Martino, Luisa; De Milito, Angelo; De Tata, Vincenzo; Debnath, Jayanta; Degterev, Alexei; Dehay, Benjamin; Delbridge, Lea M D; Demarchi, Francesca; Deng, Yi Zhen; Dengjel, Jorn; Dent, Paul; Denton, Donna; Deretic, Vojo; Desai, Shyamal D; Devenish, Rodney J; Di Gioacchino, Mario; Di Paolo, Gilbert; Di Pietro, Chiara; Diaz-Araya, Guillermo; Diaz-Laviada, Ines; Diaz-Meco, Maria T; Diaz-Nido, Javier; Dikic, Ivan; Dinesh-Kumar, Savithramma P; Ding, Wen-Xing; Distelhorst, Clark W; Diwan, Abhinav; Djavaheri-Mergny, Mojgan; Dokudovskaya, Svetlana; Dong, Zheng; Dorsey, Frank C; Dosenko, Victor; Dowling, James J; Doxsey, Stephen; Dreux, Marlene; Drew, Mark E; Duan, Qiuhong; Duchosal, Michel A; Duff, Karen; Dugail, Isabelle; Durbeej, Madeleine; Duszenko, Michael; Edelstein, Charles L; Edinger, Aimee L; Egea, Gustavo; Eichinger, Ludwig; Eissa, N Tony; Ekmekcioglu, Suhendan; El-Deiry, Wafik S; Elazar, Zvulun; Elgendy, Mohamed; Ellerby, Lisa M; Eng, Kai Er; Engelbrecht, Anna-Mart; Engelender, Simone; Erenpreisa, Jekaterina; Escalante, Ricardo; Esclatine, Audrey; Eskelinen, Eeva-Liisa; Espert, Lucile; Espina, Virginia; Fan, Huizhou; Fan, Jia; Fan, Qi-Wen; Fan, Zhen; Fang, Shengyun; Fang, Yongqi; Fanto, Manolis; Fanzani, Alessandro; Farkas, Thomas; Farre, Jean-Claude; Faure, Mathias; Fechheimer, Marcus; Feng, Carl G; Feng, Jian; Feng, Qili; Feng, Youji; Fesus, Laszlo; Feuer, Ralph; Figueiredo-Pereira, Maria E; Fimia, Gian Maria; Fingar, Diane C; Finkbeiner, Steven; Finkel, Toren; Finley, Kim D; Fiorito, Filomena; Fisher, Edward A; Fisher, Paul B; Flajolet, Marc; Florez-McClure, Maria L; Florio, Salvatore; Fon, Edward A; Fornai, Francesco; Fortunato, Franco; Fotedar, Rati; Fowler, Daniel H; Fox, Howard S; Franco, Rodrigo; Frankel, Lisa B; Fransen, Marc; Fuentes, Jose M; Fueyo, Juan; Fujii, Jun; Fujisaki, Kozo; Fujita, Eriko; Fukuda, Mitsunori; Furukawa, Ruth H; Gaestel, Matthias; Gailly, Philippe; Gajewska, Malgorzata; Galliot, Brigitte; Galy, Vincent; Ganesh, Subramaniam; Ganetzky, Barry; Ganley, Ian G; Gao, Fen-Biao; Gao, George F; Gao, Jinming; Garcia, Lorena; Garcia-Manero, Guillermo; Garcia-Marcos, Mikel; Garmyn, Marjan; Gartel, Andrei L; Gatti, Evelina; Gautel, Mathias; Gawriluk, Thomas R; Gegg, Matthew E; Geng, Jiefei; Germain, Marc; Gestwicki, Jason E; Gewirtz, David A; Ghavami, Saeid; Ghosh, Pradipta; Giammarioli, Anna M; Giatromanolaki, Alexandra N; Gibson, Spencer B; Gilkerson, Robert W; Ginger, Michael L; Ginsberg, Henry N; Golab, Jakub; Goligorsky, Michael S; Golstein, Pierre; Gomez-Manzano, Candelaria; Goncu, Ebru; Gongora, Celine; Gonzalez, Claudio D; Gonzalez, Ramon; Gonzalez-Estevez, Cristina; Gonzalez-Polo, Rosa Ana; Gonzalez-Rey, Elena; Gorbunov, Nikolai V; Gorski, Sharon; Goruppi, Sandro; Gottlieb, Roberta A; Gozuacik, Devrim; Granato, Giovanna Elvira; Grant, Gary D; Green, Kim N; Gregorc, Ales; Gros, Frederic; Grose, Charles; Grunt, Thomas W; Gual, Philippe; Guan, Jun-Lin; Guan, Kun-Liang; Guichard, Sylvie M; Gukovskaya, Anna S; Gukovsky, Ilya; Gunst, Jan; Gustafsson, Asa B; Halayko, Andrew J; Hale, Amber N; Halonen, Sandra K; Hamasaki, Maho; Han, Feng; Han, Ting; Hancock, Michael K; Hansen, Malene; Harada, Hisashi; Harada, Masaru; Hardt, Stefan E; Harper, J Wade; Harris, Adrian L; Harris, James; Harris, Steven D; Hashimoto, Makoto; Haspel, Jeffrey A; Hayashi, Shin-ichiro; Hazelhurst, Lori A; He, Congcong; He, You-Wen; Hebert, Marie-Josee; Heidenreich, Kim A; Helfrich, Miep H; Helgason, Gudmundur V; Henske, Elizabeth P; Herman, Brian; Herman, Paul K; Hetz, Claudio; Hilfiker, Sabine; Hill, Joseph A; Hocking, Lynne J; Hofman, Paul; Hofmann, Thomas G; Hohfeld, Jorg; Holyoake, Tessa L; Hong, Ming-Huang; Hood, David A; Hotamisligil, Gokhan S; Houwerzijl, Ewout J; Hoyer-Hansen, Maria; Hu, Bingren; Hu, Chien-An A; Hu, Hong-Ming; Hua, Ya; Huang, Canhua; Huang, Ju; Huang, Shengbing; Huang, Wei-Pang; Huber, Tobias B; Huh, Won-Ki; Hung, Tai-Ho; Hupp, Ted R; Hur, Gang Min; Hurley, James B; Hussain, Sabah N A; Hussey, Patrick J; Hwang, Jung Jin; Hwang, Seungmin; Ichihara, Atsuhiro; Ilkhanizadeh, Shirin; Inoki, Ken; Into, Takeshi; Iovane, Valentina; Iovanna, Juan L; Ip, Nancy Y; Isaka, Yoshitaka; Ishida, Hiroyuki; Isidoro, Ciro; Isobe, Ken-ichi; Iwasaki, Akiko; Izquierdo, Marta; Izumi, Yotaro; Jaakkola, Panu M; Jaattela, Marja; Jackson, George R; Jackson, William T; Janji, Bassam; Jendrach, Marina; Jeon, Ju-Hong; Jeung, Eui-Bae; Jiang, Hong; Jiang, Hongchi; Jiang, Jean X; Jiang, Ming; Jiang, Qing; Jiang, Xuejun; Jiang, Xuejun; Jimenez, Alberto; Jin, Meiyan; Jin, Shengkan; Joe, Cheol O; Johansen, Terje; Johnson, Daniel E; Johnson, Gail V W; Jones, Nicola L; Joseph, Bertrand; Joseph, Suresh K; Joubert, Annie M; Juhasz, Gabor; Juillerat-Jeanneret, Lucienne; Jung, Chang Hwa; Jung, Yong-Keun; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kadowaki, Motoni; Kagedal, Katarina; Kamada, Yoshiaki; Kaminskyy, Vitaliy O; Kampinga, Harm H; Kanamori, Hiromitsu; Kang, Chanhee; Kang, Khong Bee; Kang, Kwang Il; Kang, Rui; Kang, Yoon-A; Kanki, Tomotake; Kanneganti, Thirumala-Devi; Kanno, Haruo; Kanthasamy, Anumantha G; Kanthasamy, Arthi; Karantza, Vassiliki; Kaushal, Gur P; Kaushik, Susmita; Kawazoe, Yoshinori; Ke, Po-Yuan; Kehrl, John H; Kelekar, Ameeta; Kerkhoff, Claus; Kessel, David H; Khalil, Hany; Kiel, Jan A K W; Kiger, Amy A; Kihara, Akio; Kim, Deok Ryong; Kim, Do-Hyung; Kim, Dong-Hou; Kim, Eun-Kyoung; Kim, Hyung-Ryong; Kim, Jae-Sung; Kim, Jeong Hun; Kim, Jin Cheon; Kim, John K; Kim, Peter K; Kim, Seong Who; Kim, Yong-Sun; Kim, Yonghyun; Kimchi, Adi; Kimmelman, Alec C; King, Jason S; Kinsella, Timothy J; Kirkin, Vladimir; Kirshenbaum, Lorrie A; Kitamoto, Katsuhiko; Kitazato, Kaio; Klein, Ludger; Klimecki, Walter T; Klucken, Jochen; Knecht, Erwin; Ko, Ben C B; Koch, Jan C; Koga, Hiroshi; Koh, Jae-Young; Koh, Young Ho; Koike, Masato; Komatsu, Masaaki; Kominami, Eiki; Kong, Hee Jeong; Kong, Wei-Jia; Korolchuk, Viktor I; Kotake, Yaichiro; Koukourakis, Michael I; Kouri Flores, Juan B; Kovacs, Attila L; Kraft, Claudine; Krainc, Dimitri; Kramer, Helmut; Kretz-Remy, Carole; Krichevsky, Anna M; Kroemer, Guido; Kruger, Rejko; Krut, Oleg; Ktistakis, Nicholas T; Kuan, Chia-Yi; Kucharczyk, Roza; Kumar, Ashok; Kumar, Raj; Kumar, Sharad; Kundu, Mondira; Kung, Hsing-Jien; Kurz, Tino; Kwon, Ho Jeong; La Spada, Albert R; Lafont, Frank; Lamark, Trond; Landry, Jacques; Lane, Jon D; Lapaquette, Pierre; Laporte, Jocelyn F; Laszlo, Lajos; Lavandero, Sergio; Lavoie, Josee N; Layfield, Robert; Lazo, Pedro A; Le, Weidong; Le Cam, Laurent; Ledbetter, Daniel J; Lee, Alvin J X; Lee, Byung-Wan; Lee, Gyun Min; Lee, Jongdae; Lee, Ju-Hyun; Lee, Michael; Lee, Myung-Shik; Lee, Sug Hyung; Leeuwenburgh, Christiaan; Legembre, Patrick; Legouis, Renaud; Lehmann, Michael; Lei, Huan-Yao; Lei, Qun-Ying; Leib, David A; Leiro, Jose; Lemasters, John J; Lemoine, Antoinette; Lesniak, Maciej S; Lev, Dina; Levenson, Victor V; Levine, Beth; Levy, Efrat; Li, Faqiang; Li, Jun-Lin; Li, Lian; Li, Sheng; Li, Weijie; Li, Xue-Jun; Li, Yan-bo; Li, Yi-Ping; Liang, Chengyu; Liang, Qiangrong; Liao, Yung-Feng; Liberski, Pawel P; Lieberman, Andrew; Lim, Hyunjung J; Lim, Kah-Leong; Lim, Kyu; Lin, Chiou-Feng; Lin, Fu-Cheng; Lin, Jian; Lin, Jiandie D; Lin, Kui; Lin, Wan-Wan; Lin, Weei-Chin; Lin, Yi-Ling; Linden, Rafael; Lingor, Paul; Lippincott-Schwartz, Jennifer; Lisanti, Michael P; Liton, Paloma B; Liu, Bo; Liu, Chun-Feng; Liu, Kaiyu; Liu, Leyuan; Liu, Qiong A; Liu, Wei; Liu, Young-Chau; Liu, Yule; Lockshin, Richard A; Lok, Chun-Nam; Lonial, Sagar; Loos, Benjamin; Lopez-Berestein, Gabriel; Lopez-Otin, Carlos; Lossi, Laura; Lotze, Michael T; Low, Peter; Lu, Binfeng; Lu, Bingwei; Lu, Bo; Lu, Zhen; Luciano, Frederic; Lukacs, Nicholas W; Lund, Anders H; Lynch-Day, Melinda A; Ma, Yong; Macian, Fernando; MacKeigan, Jeff P; Macleod, Kay F; Madeo, Frank; Maiuri, Luigi; Maiuri, Maria Chiara; Malagoli, Davide; Malicdan, May Christine V; Malorni, Walter; Man, Na; Mandelkow, Eva-Maria; Manon, Stephen; Manov, Irena; Mao, Kai; Mao, Xiang; Mao, Zixu; Marambaud, Philippe; Marazziti, Daniela; Marcel, Yves L; Marchbank, Katie; Marchetti, Piero; Marciniak, Stefan J; Marcondes, Mateus; Mardi, Mohsen; Marfe, Gabriella; Marino, Guillermo; Markaki, Maria; Marten, Mark R; Martin, Seamus J; Martinand-Mari, Camille; Martinet, Wim; Martinez-Vicente, Marta; Masini, Matilde; Matarrese, Paola; Matsuo, Saburo; Matteoni, Raffaele; Mayer, Andreas; Mazure, Nathalie M; McConkey, David J; McConnell, Melanie J; McDermott, Catherine; McDonald, Christine; McInerney, Gerald M; McKenna, Sharon L; McLaughlin, BethAnn; McLean, Pamela J; McMaster, Christopher R; McQuibban, G Angus; Meijer, Alfred J; Meisler, Miriam H; Melendez, Alicia; Melia, Thomas J; Melino, Gerry; Mena, Maria A; Menendez, Javier A; Menna-Barreto, Rubem F S; Menon, Manoj B; Menzies, Fiona M; Mercer, Carol A; Merighi, Adalberto; Merry, Diane E; Meschini, Stefania; Meyer, Christian G; Meyer, Thomas F; Miao, Chao-Yu; Miao, Jun-Ying; Michels, Paul A M; Michiels, Carine; Mijaljica, Dalibor; Milojkovic, Ana; Minucci, Saverio; Miracco, Clelia; Miranti, Cindy K; Mitroulis, Ioannis; Miyazawa, Keisuke; Mizushima, Noboru; Mograbi, Baharia; Mohseni, Simin; Molero, Xavier; Mollereau, Bertrand; Mollinedo, Faustino; Momoi, Takashi; Monastyrska, Iryna; Monick, Martha M; Monteiro, Mervyn J; Moore, Michael N; Mora, Rodrigo; Moreau, Kevin; Moreira, Paula I; Moriyasu, Yuji; Moscat, Jorge; Mostowy, Serge; Mottram, Jeremy C; Motyl, Tomasz; Moussa, Charbel E-H; Muller, Sylke; Muller, Sylviane; Munger, Karl; Munz, Christian; Murphy, Leon O; Murphy, Maureen E; Musaro, Antonio; Mysorekar, Indira; Nagata, Eiichiro; Nagata, Kazuhiro; Nahimana, Aimable; Nair, Usha; Nakagawa, Toshiyuki; Nakahira, Kiichi; Nakano, Hiroyasu; Nakatogawa, Hitoshi; Nanjundan, Meera; Naqvi, Naweed I; Narendra, Derek P; Narita, Masashi; Navarro, Miguel; Nawrocki, Steffan T; Nazarko, Taras Y; Nemchenko, Andriy; Netea, Mihai G; Neufeld, Thomas P; Ney, Paul A; Nezis, Ioannis P; Nguyen, Huu Phuc; Nie, Daotai; Nishino, Ichizo; Nislow, Corey; Nixon, Ralph A; Noda, Takeshi; Noegel, Angelika A; Nogalska, Anna; Noguchi, Satoru; Notterpek, Lucia; Novak, Ivana; Nozaki, Tomoyoshi; Nukina, Nobuyuki; Nurnberger, Thorsten; Nyfeler, Beat; Obara, Keisuke; Oberley, Terry D; Oddo, Salvatore; Ogawa, Michinaga; Ohashi, Toya; Okamoto, Koji; Oleinick, Nancy L; Oliver, F Javier; Olsen, Laura J; Olsson, Stefan; Opota, Onya; Osborne, Timothy F; Ostrander, Gary K; Otsu, Kinya; Ou, Jing-hsiung James; Ouimet, Mireille; Overholtzer, Michael; Ozpolat, Bulent; Paganetti, Paolo; Pagnini, Ugo; Pallet, Nicolas; Palmer, Glen E; Palumbo, Camilla; Pan, Tianhong; Panaretakis, Theocharis; Pandey, Udai Bhan; Papackova, Zuzana; Papassideri, Issidora; Paris, Irmgard; Park, Junsoo; Park, Ohkmae K; Parys, Jan B; Parzych, Katherine R; Patschan, Susann; Patterson, Cam; Pattingre, Sophie; Pawelek, John M; Peng, Jianxin; Perlmutter, David H; Perrotta, Ida; Perry, George; Pervaiz, Shazib; Peter, Matthias; Peters, Godefridus J; Petersen, Morten; Petrovski, Goran; Phang, James M; Piacentini, Mauro; Pierre, Philippe; Pierrefite-Carle, Valerie; Pierron, Gerard; Pinkas-Kramarski, Ronit; Piras, Antonio; Piri, Natik; Platanias, Leonidas C; Poggeler, Stefanie; Poirot, Marc; Poletti, Angelo; Pous, Christian; Pozuelo-Rubio, Mercedes; Praetorius-Ibba, Mette; Prasad, Anil; Prescott, Mark; Priault, Muriel; Produit-Zengaffinen, Nathalie; Progulske-Fox, Ann; Proikas-Cezanne, Tassula; Przedborski, Serge; Przyklenk, Karin; Puertollano, Rosa; Puyal, Julien; Qian, Shu-Bing; Qin, Liang; Qin, Zheng-Hong; Quaggin, Susan E; Raben, Nina; Rabinowich, Hannah; Rabkin, Simon W; Rahman, Irfan; Rami, Abdelhaq; Ramm, Georg; Randall, Glenn; Randow, Felix; Rao, V Ashutosh; Rathmell, Jeffrey C; Ravikumar, Brinda; Ray, Swapan K; Reed, Bruce H; Reed, John C; Reggiori, Fulvio; Regnier-Vigouroux, Anne; Reichert, Andreas S; Reiners, John J Jr; Reiter, Russel J; Ren, Jun; Revuelta, Jose L; Rhodes, Christopher J; Ritis, Konstantinos; Rizzo, Elizete; Robbins, Jeffrey; Roberge, Michel; Roca, Hernan; Roccheri, Maria C; Rocchi, Stephane; Rodemann, H Peter; Rodriguez de Cordoba, Santiago; Rohrer, Barbel; Roninson, Igor B; Rosen, Kirill; Rost-Roszkowska, Magdalena M; Rouis, Mustapha; Rouschop, Kasper M A; Rovetta, Francesca; Rubin, Brian P; Rubinsztein, David C; Ruckdeschel, Klaus; Rucker, Edmund B 3rd; Rudich, Assaf; Rudolf, Emil; Ruiz-Opazo, Nelson; Russo, Rossella; Rusten, Tor Erik; Ryan, Kevin M; Ryter, Stefan W; Sabatini, David M; Sadoshima, Junichi; Saha, Tapas; Saitoh, Tatsuya; Sakagami, Hiroshi; Sakai, Yasuyoshi; Salekdeh, Ghasem Hoseini; Salomoni, Paolo; Salvaterra, Paul M; Salvesen, Guy; Salvioli, Rosa; Sanchez, Anthony M J; Sanchez-Alcazar, Jose A; Sanchez-Prieto, Ricardo; Sandri, Marco; Sankar, Uma; Sansanwal, Poonam; Santambrogio, Laura; Saran, Shweta; Sarkar, Sovan; Sarwal, Minnie; Sasakawa, Chihiro; Sasnauskiene, Ausra; Sass, Miklos; Sato, Ken; Sato, Miyuki; Schapira, Anthony H V; Scharl, Michael; Schatzl, Hermann M; Scheper, Wiep; Schiaffino, Stefano; Schneider, Claudio; Schneider, Marion E; Schneider-Stock, Regine; Schoenlein, Patricia V; Schorderet, Daniel F; Schuller, Christoph; Schwartz, Gary K; Scorrano, Luca; Sealy, Linda; Seglen, Per O; Segura-Aguilar, Juan; Seiliez, Iban; Seleverstov, Oleksandr; Sell, Christian; Seo, Jong Bok; Separovic, Duska; Setaluri, Vijayasaradhi; Setoguchi, Takao; Settembre, Carmine; Shacka, John J; Shanmugam, Mala; Shapiro, Irving M; Shaulian, Eitan; Shaw, Reuben J; Shelhamer, James H; Shen, Han-Ming; Shen, Wei-Chiang; Sheng, Zu-Hang; Shi, Yang; Shibuya, Kenichi; Shidoji, Yoshihiro; Shieh, Jeng-Jer; Shih, Chwen-Ming; Shimada, Yohta; Shimizu, Shigeomi; Shintani, Takahiro; Shirihai, Orian S; Shore, Gordon C; Sibirny, Andriy A; Sidhu, Stan B; Sikorska, Beata; Silva-Zacarin, Elaine C M; Simmons, Alison; Simon, Anna Katharina; Simon, Hans-Uwe; Simone, Cristiano; Simonsen, Anne; Sinclair, David A; Singh, Rajat; Sinha, Debasish; Sinicrope, Frank A; Sirko, Agnieszka; Siu, Parco M; Sivridis, Efthimios; Skop, Vojtech; Skulachev, Vladimir P; Slack, Ruth S; Smaili, Soraya S; Smith, Duncan R; Soengas, Maria S; Soldati, Thierry; Song, Xueqin; Sood, Anil K; Soong, Tuck Wah; Sotgia, Federica; Spector, Stephen A; Spies, Claudia D; Springer, Wolfdieter; Srinivasula, Srinivasa M; Stefanis, Leonidas; Steffan, Joan S; Stendel, Ruediger; Stenmark, Harald; Stephanou, Anastasis; Stern, Stephan T; Sternberg, Cinthya; Stork, Bjorn; Stralfors, Peter; Subauste, Carlos S; Sui, Xinbing; Sulzer, David; Sun, Jiaren; Sun, Shi-Yong; Sun, Zhi-Jun; Sung, Joseph J Y; Suzuki, Kuninori; Suzuki, Toshihiko; Swanson, Michele S; Swanton, Charles; Sweeney, Sean T; Sy, Lai-King; Szabadkai, Gyorgy; Tabas, Ira; Taegtmeyer, Heinrich; Tafani, Marco; Takacs-Vellai, Krisztina; Takano, Yoshitaka; Takegawa, Kaoru; Takemura, Genzou; Takeshita, Fumihiko; Talbot, Nicholas J; Tan, Kevin S W; Tanaka, Keiji; Tanaka, Kozo; Tang, Daolin; Tang, Dingzhong; Tanida, Isei; Tannous, Bakhos A; Tavernarakis, Nektarios; Taylor, Graham S; Taylor, Gregory A; Taylor, J Paul; Terada, Lance S; Terman, Alexei; Tettamanti, Gianluca; Thevissen, Karin; Thompson, Craig B; Thorburn, Andrew; Thumm, Michael; Tian, FengFeng; Tian, Yuan; Tocchini-Valentini, Glauco; Tolkovsky, Aviva M; Tomino, Yasuhiko; Tonges, Lars; Tooze, Sharon A; Tournier, Cathy; Tower, John; Towns, Roberto; Trajkovic, Vladimir; Travassos, Leonardo H; Tsai, Ting-Fen; Tschan, Mario P; Tsubata, Takeshi; Tsung, Allan; Turk, Boris; Turner, Lorianne S; Tyagi, Suresh C; Uchiyama, Yasuo; Ueno, Takashi; Umekawa, Midori; Umemiya-Shirafuji, Rika; Unni, Vivek K; Vaccaro, Maria I; Valente, Enza Maria; Van den Berghe, Greet; van der Klei, Ida J; van Doorn, Wouter; van Dyk, Linda F; van Egmond, Marjolein; van Grunsven, Leo A; Vandenabeele, Peter; Vandenberghe, Wim P; Vanhorebeek, Ilse; Vaquero, Eva C; Velasco, Guillermo; Vellai, Tibor; Vicencio, Jose Miguel; Vierstra, Richard D; Vila, Miquel; Vindis, Cecile; Viola, Giampietro; Viscomi, Maria Teresa; Voitsekhovskaja, Olga V; von Haefen, Clarissa; Votruba, Marcela; Wada, Keiji; Wade-Martins, Richard; Walker, Cheryl L; Walsh, Craig M; Walter, Jochen; Wan, Xiang-Bo; Wang, Aimin; Wang, Chenguang; Wang, Dawei; Wang, Fan; Wang, Fen; Wang, Guanghui; Wang, Haichao; Wang, Hong-Gang; Wang, Horng-Dar; Wang, Jin; Wang, Ke; Wang, Mei; Wang, Richard C; Wang, Xinglong; Wang, Xuejun; Wang, Ying-Jan; Wang, Yipeng; Wang, Zhen; Wang, Zhigang Charles; Wang, Zhinong; Wansink, Derick G; Ward, Diane M; Watada, Hirotaka; Waters, Sarah L; Webster, Paul; Wei, Lixin; Weihl, Conrad C; Weiss, William A; Welford, Scott M; Wen, Long-Ping; Whitehouse, Caroline A; Whitton, J Lindsay; Whitworth, Alexander J; Wileman, Tom; Wiley, John W; Wilkinson, Simon; Willbold, Dieter; Williams, Roger L; Williamson, Peter R; Wouters, Bradly G; Wu, Chenghan; Wu, Dao-Cheng; Wu, William K K; Wyttenbach, Andreas; Xavier, Ramnik J; Xi, Zhijun; Xia, Pu; Xiao, Gengfu; Xie, Zhiping; Xie, Zhonglin; Xu, Da-zhi; Xu, Jianzhen; Xu, Liang; Xu, Xiaolei; Yamamoto, Ai; Yamamoto, Akitsugu; Yamashina, Shunhei; Yamashita, Michiaki; Yan, Xianghua; Yanagida, Mitsuhiro; Yang, Dun-Sheng; Yang, Elizabeth; Yang, Jin-Ming; Yang, Shi Yu; Yang, Wannian; Yang, Wei Yuan; Yang, Zhifen; Yao, Meng-Chao; Yao, Tso-Pang; Yeganeh, Behzad; Yen, Wei-Lien; Yin, Jia-jing; Yin, Xiao-Ming; Yoo, Ook-Joon; Yoon, Gyesoon; Yoon, Seung-Yong; Yorimitsu, Tomohiro; Yoshikawa, Yuko; Yoshimori, Tamotsu; Yoshimoto, Kohki; You, Ho Jin; Youle, Richard J; Younes, Anas; Yu, Li; Yu, Long; Yu, Seong-Woon; Yu, Wai Haung; Yuan, Zhi-Min; Yue, Zhenyu; Yun, Cheol-Heui; Yuzaki, Michisuke; Zabirnyk, Olga; Silva-Zacarin, Elaine; Zacks, David; Zacksenhaus, Eldad; Zaffaroni, Nadia; Zakeri, Zahra; Zeh, Herbert J 3rd; Zeitlin, Scott O; Zhang, Hong; Zhang, Hui-Ling; Zhang, Jianhua; Zhang, Jing-Pu; Zhang, Lin; Zhang, Long; Zhang, Ming-Yong; Zhang, Xu Dong; Zhao, Mantong; Zhao, Yi-Fang; Zhao, Ying; Zhao, Zhizhuang J; Zheng, Xiaoxiang; Zhivotovsky, Boris; Zhong, Qing; Zhou, Cong-Zhao; Zhu, Changlian; Zhu, Wei-Guo; Zhu, Xiao-Feng; Zhu, Xiongwei; Zhu, Yuangang; Zoladek, Teresa; Zong, Wei-Xing; Zorzano, Antonio; Zschocke, Jurgen; Zuckerbraun, Brian
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
PMCID:3404883
PMID: 22966490
ISSN: 1554-8627
CID: 181862

Viruses, autophagy genes, and Crohn's disease

Hubbard, Vanessa M; Cadwell, Ken
The etiology of the intestinal disease Crohn's disease involves genetic factors as well as ill-defined environmental agents. Several genetic variants linked to this disease are associated with autophagy, a process that is critical for proper responses to viral infections. While a role for viruses in this disease remains speculative, accumulating evidence indicate that this possibility requires serious consideration. In this review, we will examine the three-way relationship between viruses, autophagy genes, and Crohn's disease and discuss how host-pathogen interactions can mediate complex inflammatory disorders
PMCID:3185787
PMID: 21994779
ISSN: 1999-4915
CID: 150323

Crohn's disease susceptibility gene interactions, a NOD to the newcomer ATG16L1 [Comment]

Cadwell, Ken
PMID: 20875485
ISSN: 0016-5085
CID: 232322

Quantitation of selective autophagic protein aggregate degradation in vitro and in vivo using luciferase reporters (vol 5, pg 511, 2009) [Correction]

Ju, Jeong-Sun; Miller, Sara E.; Jackson, Erin; Cadwell, Ken; Piwnica-Worms, David; Weihl, Conrad C.
ISI:000279429200022
ISSN: 1554-8627
CID: 3588712

Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine

Cadwell, Ken; Patel, Khushbu K; Maloney, Nicole S; Liu, Ta-Chiang; Ng, Aylwin C Y; Storer, Chad E; Head, Richard D; Xavier, Ramnik; Stappenbeck, Thaddeus S; Virgin, Herbert W
It is unclear why disease occurs in only a small proportion of persons carrying common risk alleles of disease susceptibility genes. Here we demonstrate that an interaction between a specific virus infection and a mutation in the Crohn's disease susceptibility gene Atg16L1 induces intestinal pathologies in mice. This virus-plus-susceptibility gene interaction generated abnormalities in granule packaging and unique patterns of gene expression in Paneth cells. Further, the response to injury induced by the toxic substance dextran sodium sulfate was fundamentally altered to include pathologies resembling aspects of Crohn's disease. These pathologies triggered by virus-plus-susceptibility gene interaction were dependent on TNFalpha and IFNgamma and were prevented by treatment with broad spectrum antibiotics. Thus, we provide a specific example of how a virus-plus-susceptibility gene interaction can, in combination with additional environmental factors and commensal bacteria, determine the phenotype of hosts carrying common risk alleles for inflammatory disease.
PMCID:2908380
PMID: 20602997
ISSN: 0092-8674
CID: 232332

Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes

Stephenson, Linda M; Miller, Brian C; Ng, Aylwin; Eisenberg, Jason; Zhao, Zijiang; Cadwell, Ken; Graham, Daniel B; Mizushima, Noboru N; Xavier, Ramnik; Virgin, Herbert W; Swat, Wojciech
Autophagy is implicated in many functions of mammalian cells such as organelle recycling, survival and differentiation, and is essential for the maintenance of T and B lymphocytes. Here, we demonstrate that autophagy is a constitutive process during T cell development. Deletion of the essential autophagy genes Atg5 or Atg7 in T cells resulted in decreased thymocyte and peripheral T cell numbers, and Atg5-deficient T cells had a decrease in cell survival. We employed functional-genetic and integrative computational analyses to elucidate specific functions of the autophagic process in developing T-lineage lymphocytes. Our whole-genome transcriptional profiling identified a set of 699 genes differentially expressed in Atg5-deficient and Atg5-sufficient thymocytes (Atg5-dependent gene set). Strikingly, the Atg5-dependent gene set was dramatically enriched in genes encoding proteins associated with the mitochondrion. In support of a role for autophagy in mitochondrial maintenance in T lineage cells, the deletion of Atg5 led to increased mitochondrial mass in peripheral T cells. We also observed a correlation between mitochondrial mass and Annexin-V staining in peripheral T cells. We propose that autophagy is critical for mitochondrial maintenance and T cell survival. We speculate that, similar to its role in yeast or mammalian liver cells, autophagy is required in T cells for the removal of damaged or aging mitochondria and that this contributes to the cell death of autophagy-deficient T cells.
PMCID:3737142
PMID: 19276668
ISSN: 1554-8627
CID: 232372

Quantitation of selective autophagic protein aggregate degradation in vitro and in vivo using luciferase reporters

Ju, Jeong-Sun; Miller, Sara E; Jackson, Erin; Cadwell, Ken; Piwnica-Worms, David; Weihl, Conrad C
The analysis of autophagy in cells and tissue has principally been performed via qualitative measures. These assays identify autophagosomes or measure the conversion of LC3I to LC3II. However, qualitative assays fail to quantitate the degradation of an autophagic substrate and therefore only indirectly measure an intact autophagic system. "Autophagic flux" can be measured using long-lived proteins that are degraded via autophagy. We developed a quantifiable luciferase reporter assay that measures the degradation of a long-lived polyglutamine protein aggregate, polyQ80-luciferase. Using this reporter, the induction of autophagy via starvation or rapamycin in cells preferentially decreases polyQ80-luciferase when compared with a nonaggregating polyQ19-luciferase after four hours of treatment. This response was both time- and concentration-dependent, prevented by autophagy inhibitors and absent in ATG5 knockout cells. We adapted this assay to living animals by electroporating polyQ19-luciferase and polyQ80-luciferase expression constructs into the right and left tibialis anterior (TA) muscles of mice, respectively. The change in the ratio of polyQ80-luciferase to polyQ19-luciferase signal before and after autophagic stimulation or inhibition was quantified via in vivo bioluminescent imaging. Following two days of starvation or treatment with intraperitoneal rapamycin, there was a approximately 35% reduction in the ratio of polyQ80:polyQ19-luciferase activity, consistent with the selective autophagic degradation of polyQ80 protein. This autophagic response in skeletal muscle in vivo was abrogated by co-treatment with chloroquine and in ATG16L1 hypomorphic mice. Our study demonstrates a method to quantify the autophagic flux of an expanded polyglutamine via luciferase reporters in vitro and in vivo.
PMCID:2992796
PMID: 19305149
ISSN: 1554-8627
CID: 232362