Selected Publications

Total 53 peer-reviewed publications, a full list can be found at:

1. Role of Sestrin against age- and obesity-associated diseases. Through Drosophila and mouse model systems, we have shown that Sestrin-family proteins are important for attenuating development of age- and obesity-associated pathologies. Most recently, we showed that Sestrin is an essential mediator of exercise in extending endurance capacity and improving metabolism.

a. Lee, J. H., Budanov, A. V., Park, E. J., Birse, R., Kim, T. E., Perkins, G. A., Ocorr, K., Ellisman, M. H., Bodmer, R., Bier, E.**, Karin, M.** (2010) Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327, 1213-1218. PMID: 20203043, PMCID: PMC2866632. [Cover Story] [**, co-corresponding authors]

b. Lee, J. H.*,**, Budanov, A. V.*, Talukdar, S., Park, E. J., Park, H. L., Park, H. W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., Wolfe, A. M., Perkins, G. A., Ellisman, M. H., Bier, E., Scadeng, M., Foretz, M., Viollet, B., Olefsky, J., Karin, M.** (2012) Maintenance of metabolic homeostasis by Sestrin 2 and Sestrin3. Cell Metab. 16, 311-321. PMID: 22958918, PMCID: PMC3687365. [* Co-first authors, ** Co-corresponding authors]

c. Lee, J. H.*, Budanov, A. V.*, and Karin, M. (2013) Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab., 18, 792-801. PMID: 24055102, PMCID: PMC3858445. [*, Co-first authors]

d. Kim, M.*, Sujkowski, A.*, Namkoong, S., Gu, B., Cobb, T., Kim, B., Kowalsky, A. H., Cho, C. S., Semple, I., Ro, S. H., Davis C., Brooks, S. V., Karin, M., Wessells, R. J.**, and Lee, J. H.** (2020) Sestrin is an evolutionarily conserved mediator of exercise. Nat. Commun., 11, 190. PMID: 31929512, PMCID: PMC6955242. [Editors’ Highlights; *, co-first authors; **, co-corresponding authors]

2. Homeostatic roles of Sestrin in tissue metabolism and tumor suppression. Subsequent studies revealed critical physiological functions of Sestrins in adipose tissue, liver and colon in regulating metabolism and suppressing tumorigenesis.

a. Ro, S. H., Nam, M., Jang, I., Park, H. W., Park, H., Semple, I. A., Kim, M., Kim, J. S., Park, H., Einatd, P., Damarid, G., Golikovd, M., Feinstein, E., and Lee, J. H. (2014) Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species. Proc. Natl. Acad. Sci. U S A 111, 7849-7854. PMID: 24825887, PMCID: PMC4040599.

b. Park, H. W., Park, H., Ro, S. H., Jang, I., Semple, I. A., Kim, D. N., Kim, M., Nam, M., Zhang, D., Yin, L., Lee, J. H. (2014) Hepatoprotective role of Sestrin2 against chronic ER stress. Nat. Commun. 5, 4233. PMID: 24947615, PMCID: PMC4074707.

c. Ro, S. H.*, Xue, X.*, Ramakrishnan, S. K., Cho, C. S., Namkoong, S., Jang, I., Semple, I. A., Ho, A., Park, H. W., Shah, Y. M.**, Lee, J. H.** (2016) Tumor suppressive role of Sestrin2 during colitis and colon carcinogenesis. Elife, 5:e12204. PMID: 26913956, PMCID: PMC4805551. [* Co-first authors, ** Co-corresponding authors]

d. Kowalsky, A.*, Namkoong, S.*, Mettetal, E., Park, H. W., Kazyken, D., Fingar, D. C., Lee, J. H. (2020) The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT activation. J. Biol. Chem. In Press. PMID: 31915252, PMCID: In Process [Editors’ Pick; *, co-first authors]

3. Molecular mechanisms underlying the physiological functions of Sestrins. We further deciphered the molecular mechanisms underlying the metabolism-controlling functions of Sestrins through biochemical and structural studies.

a. Ro, S. H., Semple, I. A., Park, H., Park, H, Park, H. W., Kim, M., Kim, J. S., and Lee, J. H. (2014) Sestrin2 promotes Unc-51-like kinase 1 (ULK1)-mediated phosphorylation of p62/sequestosome-1. FEBS J. 281, 3816-3827. PMID: 25040165, PMCID: PMC4156532.

b. Kim, J. S.*, Ro, S. H.*, Kim, M., Park, H. W., Semple, I. A., Park, H., Cho, U. S., Wang, W., Guan, K. L., Karin M., and Lee, J. H. (2015) Sestrin2 inhibits mTORC1 through modulation of GATOR complexes. Sci. Rep., 5, 9502. PMID: 25819761, PMCID: PMC4377584. [* Co-first authors]

c. Kim, H.*, An, S.*, Ro, S. H.*, Telxeira, F. P., Park, G. J., Kim, C., Cho, C. S., Kim, J. S., Jakob, U., Lee, J. H.**, Cho U. S.** (2015) Janus-faced Sestrin2 controls ROS and mTOR signaling through two separate functional domains. Nat. Commun., 6, 10025. PMID: 26612684, PMCID: PMC4674687. [* Co-first authors, ** Co-corresponding authors]

d. Ho, A., Cho, C. S., Namkoong, S., Cho, U. S., Lee, J. H. (2016) Biochemical Basis of Sestrin Physiological activities. Trends Biochem. Sci., 41, 621-632. PMID: 27174209, PMCID: PMC4930368.

4. Role of autophagy in preventing neurodegeneration and mobility disorder. Through genetic screening, we identified several autophagy regulators in Drosophila, and showed their roles in neuromuscular homeostasis. Genetic mutations in some of these autophagy-regulating genes were found to provoke familial neurodegenerative diseases in human patients.

a. Kim, M.*, Park, H. L.*, Park, H. W.*, Ro, S. H., Nam, S., Reed, J. M., Guan, J. L., Lee, J. H. (2013) Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging. Autophagy 9, 1201-1213. PMID: 23819996, PMCID: PMC3748192. [* Co-first authors]

b. Kim, M.**, Semple, I., Kim, B., Kiers, A., Nam, S., Park, H. W., Park, H., Ro, S. H., Kim, J. S., Juhász, G., Lee, J. H.** (2015) Drosophila Gyf/GRB10 interacting GYF protein is an autophagy regulator that controls neuron and muscle homeostasis. Autophagy 11, 1358-1372. PMID: 26086452, PMCID: PMC4590642. [** Co-corresponding authors]

c. Kim, M.*, Sandford, E.*, Gatica, D., Qiu, Y., Liu, X., Zheng, Y., Schulman, B. A., Xu, J., Semple, I., Ro, S. H., Kim, B., Mavioglu, R. N., Tolun, A., Jipa, A., Takats, S., Karpati, M., Li, J. Z., Yapici, Z., Juhasz, G., Lee, J. H.**, Klionsky, D. J.**, Burmeister, M.** (2016) Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay. eLife, 5:e12245. PMID: 26812546, PMCID: PMC4786408. [*, Co-first authors; **, co-corresponding authors]

d. Kim, M.**, Ho, A., Lee, J. H.** (2017) Autophagy and Human Neurodegenerative Diseases-A Fly's Perspective. Int J Mol Sci. 18:e1596. PMID: 28737703, PMCID: PMC5536083. [** Co-corresponding authors]

5. Stress-induced accumulation of protein inclusions and RNA granules. We investigated the mechanisms of how different stresses associated with obesity can impair autophagic flux and promote aggregation of proteins and RNA.

a. Park, H. W., Park, H., Semple, I. A., Jang, I., Ro, S. H., Kim, M., Cazares, V. A., Stuenkel, E. L., Kim, J. J., Kim, J. S., and Lee, J. H. (2014) Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers. Nat. Commun., 5, 4834. PMID: 25189398, PMCID: PMC4157315.

b. Cho, C. S.*, Park, H. W.*, Ho, A., Semple, I. A., Jang, I., Park, H., Reilly, S., Saltiel, A. R., Lee, J. H. (2018) Lipotoxicity induces hepatic protein inclusions through TBK1-mediated p62/SQSTM1 phosphorylation. Hepatology, 68, 1331-1346. PMID: 29251796. [*, co-first authors]

c. Namkoong, S., Ho, A., Woo, Y. M., Kwak, H. J.**, Lee, J. H.** (2018) Systematic Characterization of Stress-Induced RNA Granulation. Mol. Cell, 70, 175-187. PMID: 29576526. [Cover Story] [**, co-corresponding authors]

d. Ries, R. J., Zaccara, S., Klein, P., Olarerin-George, A., Namkoong, S., Pickering, B. F., Patil, D. P., Kwak, H., Lee, J. H., Jaffrey, S. R. (2019) m6A enhances the phase separation potential of mRNA. Nature. 571, 424-428. PMID: 31292544, PMCID: PMC6662915.