Yingming Zhao

Research Summary
Post-translational modifications (PTMs) represent a major vehicle to diversify a cellular proteome, the inventory of all protein species in an organism. PTMs have critical roles in all the major cellular pathways and diseases. A protein can be potentially modified by more than 300 types of post-translational modifications, which are catalyzed by enzymes encoded by more than 5% of the genome in higher eukaryotes. A combination of a dozen PTM sites in a substrate protein could lead to more than a million possible protein structures with potentially different functions. Given the high abundance and diversities of PTMs, they are likely the most complex regulatory mechanisms in cells. Despite their critical roles in cells, little is known about their biology, except several most extensively studied PTMs. Functional characterizations of PTMs at the molecular level have been slow, largely due to a lack of suitable information infrastructure and technology infrastructure.
Keywords
Proteomics, epigenetics, protein modifications, cancer, metabolism, Warburg effect
Education
  • The Rockefeller University, New York city, PhD 1997
Publications
  1. Huang H, Zhang D, Wang Y, Perez-Neut M, Han Z, Zheng YG, Hao Q, Zhao Y. Lysine benzoylation is a histone mark regulated by SIRT2. Nat Commun. 2018 08 28; 9(1):3374. View in: PubMed

  2. Huang H, Tang S, Ji M, Tang Z, Shimada M, Liu X, Qi S, Locasale JW, Roeder RG, Zhao Y, Li X. p300-Mediated Lysine 2-Hydroxyisobutyrylation Regulates Glycolysis. Mol Cell. 2018 06 07; 70(5):984. View in: PubMed

  3. Sabari BR, Tang Z, Huang H, Yong-Gonzalez V, Molina H, Kong HE, Dai L, Shimada M, Cross JR, Zhao Y, Roeder RG, Allis CD. Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation. Mol Cell. 2018 02 01; 69(3):533. View in: PubMed

  4. Huang H, Luo Z, Qi S, Huang J, Xu P, Wang X, Gao L, Li F, Wang J, Zhao W, Gu W, Chen Z, Dai L, Dai J, Zhao Y. Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway. Cell Res. 2018 01; 28(1):111-125. View in: PubMed

  5. Lombard DB, Zhao Y. ACSF3 and Mal(onate)-Adapted Mitochondria. Cell Chem Biol. 2017 Jun 22; 24(6):649-650. View in: PubMed

  6. Sabari BR, Zhang D, Allis CD, Zhao Y. Metabolic regulation of gene expression through histone acylations. Nat Rev Mol Cell Biol. 2017 02; 18(2):90-101. View in: PubMed

  7. Xie Z, Zhang D, Chung D, Tang Z, Huang H, Dai L, Qi S, Li J, Colak G, Chen Y, Xia C, Peng C, Ruan H, Kirkey M, Wang D, Jensen LM, Kwon OK, Lee S, Pletcher SD, Tan M, Lombard DB, White KP, Zhao H, Li J, Roeder RG, Yang X, Zhao Y. Metabolic Regulation of Gene Expression by Histone Lysine ß-Hydroxybutyrylation. Mol Cell. 2016 04 21; 62(2):194-206. View in: PubMed

  8. Colak G, Pougovkina O, Dai L, Tan M, Te Brinke H, Huang H, Cheng Z, Park J, Wan X, Liu X, Yue WW, Wanders RJ, Locasale JW, Lombard DB, de Boer VC, Zhao Y. Proteomic and Biochemical Studies of Lysine Malonylation Suggest Its Malonic Aciduria-associated Regulatory Role in Mitochondrial Function and Fatty Acid Oxidation. Mol Cell Proteomics. 2015 Nov; 14(11):3056-71. View in: PubMed

  9. Huang H, Sabari BR, Garcia BA, Allis CD, Zhao Y. SnapShot: histone modifications. Cell. 2014 Oct 09; 159(2):458-458.e1. View in: PubMed

  10. Tan M, Peng C, Anderson KA, Chhoy P, Xie Z, Dai L, Park J, Chen Y, Huang H, Zhang Y, Ro J, Wagner GR, Green MF, Madsen AS, Schmiesing J, Peterson BS, Xu G, Ilkayeva OR, Muehlbauer MJ, Braulke T, Mühlhausen C, Backos DS, Olsen CA, McGuire PJ, Pletcher SD, Lombard DB, Hirschey MD, Zhao Y. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014 Apr 01; 19(4):605-17. View in: PubMed

  11. Dai L, Peng C, Montellier E, Lu Z, Chen Y, Ishii H, Debernardi A, Buchou T, Rousseaux S, Jin F, Sabari BR, Deng Z, Allis CD, Ren B, Khochbin S, Zhao Y. Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark. Nat Chem Biol. 2014 May; 10(5):365-70. View in: PubMed

  12. Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell. 2013 Jun 27; 50(6):919-30. View in: PubMed

  13. Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, Lu Z, Ye Z, Zhu Q, Wysocka J, Ye Y, Khochbin S, Ren B, Zhao Y. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011 Sep 16; 146(6):1016-28. View in: PubMed

  14. Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics. 2011 Dec; 10(12):M111.012658. View in: PubMed

  15. Chen Y, Chen W, Cobb MH, Zhao Y. PTMap--a sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites. Proc Natl Acad Sci U S A. 2009 Jan 20; 106(3):761-6. View in: PubMed