- Capital Institute of Medicine, Beijing, China, 1986
Areas of Interest
EPAC-mediated cell signaling: physiological functions and roles in human diseases
Adenosine 3′,5′-cyclic monophosphate (cAMP)is the prototypic second messenger that regulates a multitude of important biological processes under both physiological and pathological conditions, including diabetes, heart failure, and cancer. In eukaryotic cells, the effects of cAMP are mainly mediated by two ubiquitously expressed intracellular cAMP receptors, the classic cAMP-dependent protein kinase (PKA) and exchange protein directly activated by cAMP (EPAC). My research focus is on elucidating the physiological functions of EPAC proteins and their roles in human diseases.
We apply both genetic and pharmacological approaches to gain understanding of EPAC proteins. We have developed high throughput screen assays, successfully identified novel EPAC specific inhibitors. In collaboration with Dr. Chen at UCSD we have generated EPAC knock out mouse models, which allow us to reveal that EPAC signaling is involved in the development of multiple pathological conditions. With the combination of EPAC specific inhibitors and knockout mouse models, we are in an ideal position to answer important biological questions and to develop potential therapeutics for the treatment of human diseases where EPAC proteins are implicated.
- Almahariq M, Mei F, and Cheng X. (2014). cAMP Sensor EPAC Proteins and Energy Homeostasis. Trends Endocrin Metabol, 25:60-71.
- Tao T, Mei F, Agrawal A, Peters CJ, Ksiazek T, Cheng X*, and Tseng CT.* (2014). Blocking of Exchange Proteins Directly Activated by cAMP (Epac) Leads to Reduced Replication of Middle East Respiratory Syndrome-Coronavirus. J Virology, Epub ahead of print Jan. 22.
- Gong B*, Shelite T, Mei F, Ha T, Xu G, Chang Q, Hu Y, Wakamiya M, Ksiazek TG, Boor PJ, Bouyer R, Popov V, Chen J, Walker DH, and Cheng X.* (2013). Exchange protein directly activated by cAMP plays critical role in fatal rickettsioses. Proc Acad Natl Sci, USA, 110:19615-19620.
- Almahariq M, Tsalkova T, Mei FC, Chen H, Zhou J, Sastry SK, Schwede F, and Cheng X. (2013). A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Molec Pharm, 83:122-128.
- Yan J, Mei FC, Cheng HQ, Lao DH, Hu Y, Wei J, Patrikeev I, Hao D, Stutz SJ, Dineley KT, Motamedi M, Hommel JD, Cunningham KA, Chen J*, and Cheng X*. (2013). Enhanced leptin sensitivity, reduced adiposity and improved glucose homeostasis in mice lacking of exchange protein directly activated by cAMP isoform 1. Molec Cell Bio, 33:918-926.
- Chen H, Tsalkova T, Mei FC, Cheng X.*, and Zhou J.* (2013). Identification and characterization of small molecules as potent and specific EPAC antagonists. J Med Chem, 56:952-962.
- Peng Z, Ji Z, Mei FC, Lu M, Zhou W, Ou Y, Cheng X. (2013). Lithium Inhibits Tumorigenic Potential of PDA Cells through Targeting Hedgehog-GLI Signaling Pathway. PLOS ONE, 8, e61457.
- Tsalkova T, Mei FC, Li Sheng, Chepurny OG, Liu T, Woods Jr., VL, Holz GG, and Cheng X. (2012). Isoform-specific antagonists of exchange protein directly activated by cAMP. Proc Acad Natl Sci, USA, 109:18613-18618.
- Tsalkova T, Mei FC, and Cheng X. (2012). A Fluorescence-based High-throughput Assay for the discovery of Exchange Protein directly Activated by Cyclic AMP (EPAC) Antagonists. PLOS ONE, 7(1):e30441.
- Chen H, Tsalkova T, Mei FC, Hu Y, Cheng X.*, and Zhou J.* (2012). 5-Cyano-6-oxo-1,6-dihydro-pyrimidines as Potent Antagonists Targeting Exchange Proteins Directly Activated by cAMP. Bioorganic & Medicinal Chem Lttrs. 22:4038-4043.
- Ji Z, Mei FC, and Cheng X. (2010). Epac, not PKA catalytic subunit, is required for 3T3-L1 preadipocyte differentiation. Front Biosci (Elite Ed). 2:392-398.
- Ji Z, Mei FC, Miller AL, Thompson EB, and Cheng X. (2008). Protein kinase A (PKA) isoform RIIβ mediates the synergistic killing effect of cAMP and glucocorticoid in acute lymphoblastic leukemia cells. J Biol Chem, 283:21920-21925.
- Cheng X, Ji Z, Tsalkova T, and Mei FC. (2008). Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochimica et Biophysica Sinica. 40:651-662.
- Young TW, Mei FC, Rosen DG, Yang G, Li N, Liu J, and Cheng X. (2007). Up-regulation of Tumor Susceptibility Gene 101 Protein in Human Epithelial Ovarian Cancer Revealed by functional proteomics. Mol Cell Proteomics. 6:294-304.
- Ji Z, Mei FC, Xie J, and Cheng X. (2007). Oncogenic KRAS suppresses GLI1 degradation and activates hedgehog signaling pathway in pancreatic cancer cells. J Biol Chem, 282:14048-14055.
- Young TW, Rosen DG, Mei F, Li N, Liu J, and Cheng X. (2007). Up-regulation of Tumor Susceptibility Gene 101 Conveys poor Prognosis through Suppression of p21 Expression in Ovarian Cancer. Clinic Can Res, 13:3848-3854.
- Ji Z, Mei FC, Johnson BH, Thompson EB, and Cheng X. (2007). PKA, not Epac, suppresses hedgehog activity and regulates glucocorticoid sensitivity in acute lymphoblastic leukemia cells. J Biol Chem, 282:37370-37377.