Yuguang ‘Roger’ Shi, Ph.D.
Joe R. & Teresa Lozano Long Distinguished Chair in Metabolic Biology, Professor of Pharmacology, Barshop Institute for Longevity and Aging Studies, and UTHSCSA
Personal Statement:
Our research work focuses on translational medicine of aging and age-related disorders. Our groundbreaking work in the last 20 years has resolved one of the most challenging issues in aging research by identifying cardiolipin remodeling by the ALCAT1 enzyme as the key regulator of mitochondrial free radical aging clock, linking mitochondrial etiology of aging to the development of all age-related metabolic diseases, including type 2 diabetes, diabetic complications (retinopathy, nephropathy, and cardiomyopathy), obesity, cardiovascular diseases, heart failure, and neurodegenerative diseases. Using mice with targeted deletion of the ALCAT1 gene and a highly potent small molecule inhibitor known as Dafaglitapin initially developed by my lab, we have demonstrated all age-related diseases can be treated as a single disorder. Our landmark discovery of the PERK kinase (also known as PEK) at Lilly research Laboratories has made significant contribution to the field of ER-stress and translational control. This work is widely recognized in the field that led to the recognition of Dr. Peter Walter, who pioneered the discovery of IRE1 and XBP1 in the ER-stress field of research (Cell, 107, 827–830), as a recipient of a Lasker Award in 2014. Our lab also pioneered the cloning and characterization of a whole family of acyltransferases involved in phospholipid remodeling, including ALCAT1, LPGAT1, and MGAT2, which has become the textbook of knowledge.
Education
Ph.D., Molecular Biology, Australian National University, Australia, 1992
M.S., Genetics, University of New England, Australia, 1986
B.S., Animal Science, Northwestern A&F University, China, 1982
Lab Members
Dr. Jun Zhang – Assistant Professor/Research
Mr. Qianqian Ye – IBMS Graduate Student
Ms. Yixuan Ma – Visiting Graduate Student
Mr. Chengbin Xu – Visiting Graduate Student
Ms. Jie Zhou – Visiting Graduate Student
Publications
- Zhang, J. and Shi, Y. (2024) A 5′ -uORF links oxidative stress to translational control of ALCAT1 through phosphorylation of eIF2α. Free Radical Biol. & Med. 214:129-136.
- Sun, H., Zhang, J., Liu, X., Yang, X., Ye, Q., Zheng, Y., Han, X., Nie, J., Chuan, S., and Shi, Y. (2023) LPGAT1 Prevents the Development of MEGDEL Syndrome by Coordinating Phosphatidylglycerol Remodeling with Mitochondrial Transport, Cell Reports 42(11):113214. Spotlighted by the journal with a preview.
- Liu, X., Zhang, J., Li, J., Song, C., and Shi, Y. (2022) Pharmacological Inhibition of ALCAT1 Mitigates Amyotrophic Lateral Sclerosis by Attenuating SOD1 Protein Aggregation. Mol. Metab. Jun 28;63: 101536.
- Zhang, J. and Shi, Y. (2022) In Search of the Holy Grail: Toward a Unified Hypothesis on Mitochondrial Dysfunction in Age-Related Diseases Cells 11 (12), 1906
- Zhang, J. Nie, J., Sun, H., Li, J., Andersen, J.P., and Shi*, Y. (2022) De Novo Labeling and Trafficking of Individual Lipid Species in Live Cells. Mol. Metab. July; 61:101511
- Zhang, J. Liu, X., Nie, J., and Shi*, Y. (2022) Restoration of Mitophagy Mitigates Barth Syndrome. Autophagy 5:1-16
- He, S., Ryu, J., Liu, J., Luo, H., Lv, Y., Langlais, P.R., Wen, J., Dong, F., Sun, Z., Xia, W., Lynch, J.L., Duggirala, R., Nicholson, B., Zang, M., Shi, Y., Zhang, F., Liu, F., Bai, J., and Dong, L.Q* (2021) LRG1 is an Adipokine that Mediates Obesity-induced Hepatosteatosis and Insulin Resistance. J. Clin. Invest. 131(24): e148545.
- Jia, D., Zhang, J., Liu, X., Andersen, J.P., Tian, Z. Nie, J. Shi*, Y. (2021) Insulin Resistance in Skeletal Muscle Selectively Protects the Heart in Response to Metabolic Stress. Diabetes 70(10):2333-2343.
- Jia, D., Zhang, J., Nie, J. Andersen, J.P., Rendon, S., Zheng, Y., Liu, X.,Tian, Z, and Shi*, Y. (2021) Cardiolipin Remodeling by ALCAT1 Links Hypoxia to Coronary Artery Disease by Promoting Mitochondrial Dysfunction. Mol. Ther. S1525-0016(21)00313-0
- Andersen, J.P., Zhang, J., Sun, H., Liu, X., Liu, J. Nie, J. Shi*, Y. (2020) Aster-B Coordinates with Arf1 to Regulate Mitochondrial Cholesterol Transport. Mol. Metab. 42:101055.
- Zhang, J., Andersen, J.P., Sun, H., Nie, J., and Shi*, Y. (2020). Aster-C Coordinates with COP I Vesicles to Regulate Nutrient Sensing by mTORC1. EMBO Rep 3;21 (9): e49898.
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/yuguang.shi.1/bibliography/40647214/public/?sort=date&direction=ascending