Sekine Lab

Yusuke Sekine, PhD
Assistant Professor of Medicine
Division of Endocrinology and Metabolism
Our lab is interested in the molecular mechanisms connecting cellular metabolism with organelle function.

Yusuke Sekine Lab

Lab Focus

Our laboratory is working on the molecular mechanisms and cellular stress responses that allow a cell to adapt to metabolic alterations. Currently, we are focused on the metabolite acetyl-CoA, which plays a central role in the biosynthesis of various biomaterials, as well as in protein acetylation. We developed an experimental system to manipulate acetyl-CoA levels in cells and organisms and are investigating acetyl-CoA fluctuation-dependent functional alterations in organelles (including nucleoli, ER, mitochondria and lysosomes) and the subsequent activation of organelle-associated stress signaling pathways. A long-term goal is to understand the sensing mechanisms for various metabolite fluctuations in cells and to reveal their relevance to human aging and age-related diseases.

What question I’d like to answer

How do cells sense and respond to metabolite fluctuations?
Faculty Bio

Yusuke received his BS, Master and Ph.D. degree in Pharmaceutical Sciences from the University of Tokyo. Yusuke has focused his research career on the molecular and cellular biology of stress responses as a post-doctoral fellow and assistant professor in the Prof. Hidenori Ichijo Lab in Japan, a visiting researcher with Prof. David Ron lab at University of Cambridge in UK, and a research fellow at the National Institutes of Health in Bethesda, MD. He joined the faculty at the Aging Institute, University of Pittsburgh in October 2018.

Throughout his research career, Yusuke has been working on analyzing the molecular mechanisms underlying cellular responses to a variety of stresses including oxidative stress, proteo-toxic stress and metabolic stress. He has identified and characterized key molecules that play important roles in oxidative stress-induced cell death and immune responses using Drosophila genetic screens. Also, using somatic cell genetic approaches with CRISPR-Cas9 techniques, Yusuke uncovered a molecular target and a mechanism of action of the chemical inhibitor of the integrated stress response (ISR) that has been widely used in ISR focused research. Recently, his research group uncovered a novel stress response pathway activated by cellular metabolic stress.

Read more: Department of Medicine Faculty Profile

Selected Publications

Sekine Y, Houston R, Sekine S. Cellular metabolic stress responses via organelles. Exp Cell Res. 2021 Mar 1;400(1):112515. doi: 10.1016/j.yexcr.2021.112515. Epub 2021 Feb 11. PMID: 33582095.

Houston R, Sekine S, Calderon MJ, Seifuddin F, Wang G, Kawagishi H, Malide DA, Li Y, Gucek M, Pirooznia M, Nelson AJ, Stokes MP, Stewart-Ornstein J, Mullett SJ, Wendell SG, Watkins SC, Finkel T, Sekine Y. Acetylation-mediated remodeling of the nucleolus regulates cellular acetyl-CoA responses. PLoS Biol. 2020 Nov 30;18(11):e3000981. doi: 10.1371/journal.pbio.3000981. PMID: 33253182; PMCID: PMC7728262.

Zyryanova AF, Weis F, Faille A, Alard AA, Crespillo-Casado A, Sekine Y, Harding HP, Allen F, Parts L, Fromont C, Fischer PM, Warren AJ, Ron D. Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B. Science. 2018 Mar 30;359(6383):1533-1536. doi: 10.1126/science.aar5129. PMID: 29599245; PMCID: PMC5889100.

Sekine Y, Zyryanova A, Crespillo-Casado A, Fischer PM, Harding HP, Ron D. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science. 2015 May 29;348(6238):1027-30. doi: 10.1126/science.aaa6986. Epub 2015 Apr 9. PMID: 25858979; PMCID: PMC4538794.

Sekine Y, Hatanaka R, Watanabe T, Sono N, Iemura S, Natsume T, Kuranaga E, Miura M, Takeda K, Ichijo H. The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5. Mol Cell. 2012 Dec 14;48(5):692-704. doi: 10.1016/j.molcel.2012.09.018. Epub 2012 Oct 25. PMID: 23102700.

Current Lab Members

Ryan Houston, BS – Laboratory Research Technician

Research Support