Dr. Cunqi Ye is an Assistant Instructor in the Department of Biochemistry at the University of Texas Southwestern Medical Center. He received his B.S. in Biology from Nanjing University in China and his Ph.D. in Biological Sciences from Wayne State University in Detroit under the mentorship of Dr. Miriam Greenberg. As a graduate student, his dissertation research focuses on elucidation of molecular mechanisms underlying the regulation of phospholipid synthesis. He showed for the first time in both yeast and mammalian model systems that the ability of cells to synthesize inositol is under the control of a highly energetic inositol derivative, inositol pyrophosphate (Ye et al., JBC. 2013; Yu & Ye et al., JBC. 2016). Another focus of his graduate research is cardiolipin biology. The importance of cardiolipin research is underscored by a life-threatening disorder known as Barth syndrome caused by the loss of function of tafazzin in humans. Dr. Ye discovered that deletion of cardiolipin-specific lipase rescues growth and lifespan defects in the tafazzin mutant, and regulation of this lipase is critical for mitochondrial respiration and integrity (Ye et al., JBC. 2014).
In 2015, Dr. Ye joined the laboratory of Dr. Benjamin Tu and began his postdoctoral training at UT Southwestern Medical Center. His postdoctoral research focuses on how S-adenosylmethionine (SAM), a major biological methyl donor, is sensed by and coordinated with metabolic processes. He discovered an unforeseen metabolic function for phospholipid and histone methylation (Ye et al., Mol. Cell. 2017) and a SAM-sensing mechanism underpinning a novel coupling between demethylation of the major protein phosphatase PP2A and histones (Ye et al., Mol. Cell. 2019), and proposed a provocative hypothesis that epigenetic modifications of histones can act as repositories that influence cellular metabolism (Ye and Tu, Trends Endocrinol Metab. 2018). In particular, he found that phospholipid methylation acts as a primary methyl sink to facilitate SAM turnover for the synthesis of cysteine and glutathione, and cells lacking phospholipid methylation are sensitive to oxidative stress and exhibit hypermethylation of histones. These findings underscore an underappreciated membrane-to-chromatin communication, which further led to the discovery of histones as a nuclear methyl sink. He also found that such a metabolic function for bulk histone methylation could supersede a role in transcriptional regulation. He recently unveiled a specific mechanism whereby SAM-responsive demethylation of PP2A promotes histone demethylation by increasing chromatin binding of a specific histone demethylase through regulation of the phosphorylation status of this enzyme (Ye et al., Mol. Cell. 2019). Overall, his postdoctoral research has led to surprising discoveries of metabolic functions and underlying mechanisms for phospholipids and chromatin regulation, which illustrates fundamental principles of biology intrinsic to the life of a cell.
Dr. Ye’s long-term scientific goals are to study the function and regulation of membrane lipid synthesis, and how dysfunction of lipid metabolism is related to human disorders. He is currently investigating cellular and physiological basis for regulation of phospholipid methylation, and how synthesis of phospholipids influences redox metabolism.
- Histone methylation and demethylation
- Nutrient sensing and regulation of cellular homeostasis
- S-adenosylmethionine (SAM) metabolism
- Synthesis and function of membrane phospholipids
- Demethylation of the Protein Phosphatase PP2A Promotes Demethylation of Histones to Enable Their Function as a Methyl Group Sink.
- Ye C, Sutter BM, Wang Y, Kuang Z, Zhao X, Yu Y, Tu BP Mol. Cell 2019 Feb
- Sink into the Epigenome: Histones as Repositories That Influence Cellular Metabolism.
- Ye C, Tu BP Trends Endocrinol. Metab. 2018 Jul
- A Metabolic Function for Phospholipid and Histone Methylation.
- Ye C, Sutter BM, Wang Y, Kuang Z, Tu BP Mol. Cell 2017 Apr 66 2 180-193.e8
- Inositol Hexakisphosphate Kinase 1 (IP6K1) Regulates Inositol Synthesis in Mammalian Cells.
- Yu W, Ye C, Greenberg ML J. Biol. Chem. 2016 May 291 20 10437-44
- Inositol synthesis regulates the activation of GSK-3a in neuronal cells.
- Ye C, Greenberg ML J. Neurochem. 2015 Apr 133 2 273-83
- The Role of Cardiolipin in Cardiovascular Health.
- Shen Z, Ye C, McCain K, Greenberg ML Biomed Res Int 2015 2015 891707
- Cardiolipin remodeling: a regulatory hub for modulating cardiolipin metabolism and function.
- Ye C, Shen Z, Greenberg ML J. Bioenerg. Biomembr. 2014 Nov
- Deletion of the Cardiolipin-specific Phospholipase Cld1 Rescues Growth and Life Span Defects in the Tafazzin Mutant: IMPLICATIONS FOR BARTH SYNDROME.
- Ye C, Lou W, Li Y, Chatzispyrou IA, Hüttemann M, Lee I, Houtkooper RH, Vaz FM, Chen S, Greenberg ML J. Biol. Chem. 2014 Feb 289 6 3114-25
- Regulation of inositol metabolism is fine-tuned by inositol pyrophosphates in Saccharomyces cerevisiae.
- Ye C, Bandara WM, Greenberg ML J. Biol. Chem. 2013 Aug 288 34 24898-908
Honors & Awards
- Chilton Fellowship Award (2017)
- Deans Discretionary Award (2019)
- NIH/NIGMS K99/R00 Pathway to Independence Award (2018-)
- Thomas C. Rumble University Graduate Fellowship (2008, 2013)
- WSU Dissertation Fellowship (2013)