Nicholas J Cowan

Biosketch / Results /

Nicholas Cowan

Professor, Department of Biochemistry and Molecular Pharmacology

Contact Info

Address
550 First Avenue
New York, NY 10016

212/263-5809
Nicholas.Cowan@nyumc.org

Research Summary

The final stage in the flow of information from encoded DNA to expressed proteins is the folding of each protein into its correct three-dimensional structure. In principle, such folding reactions can occur spontaneously because all the necessary information required to determine proper folding is contained within the primary amino acid sequence. However, under physiological conditions, constraints of temperature and the tendency of unfolded proteins to aggregate are such that many proteins must undergo facilitated folding via interaction with one or more protein complexes termed chaperonins. We are concerned with the mechanism whereby proteins in the eukaryotic cytosol, such as actin and tubulin, are folded via interaction with the cytoplasmic chaperonin, a heteromeric double toroid that provides a sequestered environment in which the unscrambling of aberrantly folded target proteins can occur. We are studying the nature of target proteins that interact with the chaperonin, the function of various cofactors that modulate the folding reaction, and the role of ATP hydrolysis in chaperonin-mediated folding.

Research Interests

Protein Folding in the Eukaryotic Cytosol

Mutations in TUBB8 and Human Oocyte Meiotic Arrest
Feng, Ruizhi; Sang, Qing; Kuang, Yanping; Sun, Xiaoxi; Yan, Zheng; Zhang, Shaozhen; Shi, Juanzi; Tian, Guoling; Luchniak, Anna; Fukuda, Yusuke; Li, Bin; Yu, Min; Chen, Junling; Xu, Yao; Guo, Luo; Qu, Ronggui; Wang, Xueqian; Sun, Zhaogui; Liu, Miao; Shi, Huijuan; Wang, Hongyan; Feng, Yi; Shao, Ruijin; Chai, Renjie; Li, Qiaoli; Xing, Qinghe; Zhang, Rui; Nogales, Eva; Jin, Li; He, Lin; Gupta, Mohan L Jr; Cowan, Nicholas J; Wang, Lei. Mutations in TUBB8 and Human Oocyte Meiotic Arrest. New England journal of medicine. 2016 Jan 21;374(3):223-232 (1921572)

Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type
Isrie, Mala; Breuss, Martin; Tian, Guoling; Hansen, Andi Harley; Cristofoli, Francesca; Morandell, Jasmin; Kupchinsky, Zachari A; Sifrim, Alejandro; Rodriguez-Rodriguez, Celia Maria; Dapena, Elena Porta; Doonanco, Kurston; Leonard, Norma; Tinsa, Faten; Moortgat, Stephanie; Ulucan, Hakan; Koparir, Erkan; Karaca, Ender; Katsanis, Nicholas; Marton, Valeria; Vermeesch, Joris Robert; Davis, Erica E; Cowan, Nicholas J; Keays, David Anthony; Van Esch, Hilde. Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type. American journal of human genetics. 2015 Dec 3;97(6):790-800 (1869572)

Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly
Poirier, Karine; Lebrun, Nicolas; Broix, Loic; Tian, Guoling; Saillour, Yoann; Boscheron, Cecile; Parrini, Elena; Valence, Stephanie; Pierre, Benjamin Saint; Oger, Madison; Lacombe, Didier; Genevieve, David; Fontana, Elena; Darra, Franscesca; Cances, Claude; Barth, Magalie; Bonneau, Dominique; Bernadina, Bernardo Dalla; N'guyen, Sylvie; Gitiaux, Cyril; Parent, Philippe; des Portes, Vincent; Pedespan, Jean Michel; Legrez, Victoire; Castelnau-Ptakine, Laetitia; Nitschke, Patrick; Hieu, Thierry; Masson, Cecile; Zelenika, Diana; Andrieux, Annie; Francis, Fiona; Guerrini, Renzo; Cowan, Nicholas J; Bahi-Buisson, Nadia; Chelly, Jamel. Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nature genetics. 2013 Apr 21;45(6):639-647 (394952)

Tubulin-Specific Chaperones: Components of a Molecular Machine That Assembles the alpha/beta Heterodimer
Tian, Guoling; Cowan, Nicholas J. Tubulin-Specific Chaperones: Components of a Molecular Machine That Assembles the alpha/beta Heterodimer. Methods in cell biology. 2013 ;115:155-171 (512962)

Mutations in the beta-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities
Breuss, Martin; Heng, Julian Ik-Tsen; Poirier, Karine; Tian, Guoling; Jaglin, Xavier Hubert; Qu, Zhengdong; Braun, Andreas; Gstrein, Thomas; Ngo, Linh; Haas, Matilda; Bahi-Buisson, Nadia; Moutard, Marie-Laure; Passemard, Sandrine; Verloes, Alain; Gressens, Pierre; Xie, Yunli; Robson, Kathryn J H; Rani, Deepa Selvi; Thangaraj, Kumarasamy; Clausen, Tim; Chelly, Jamel; Cowan, Nicholas Justin; Keays, David Anthony. Mutations in the beta-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities. Cell reports. 2012 Dec 13;2(6):1554-1562 (249192)