Biography

Dr. Cheng received his bachelor’s degree at Peking University in Beijing, China and his master’s degree from Shanghai Institute of Biochemistry, Chinese Academy of Science before coming to Texas to obtain his PhD at the University of Texas Medical Branch in Galveston (UTMB). He completed his postdoctoral studies with Dr. Susan Taylor at UC San Diego and then returned to UTMB in 1999 to start his own laboratory. In December 2013, Dr. Cheng joined the faculty of the Department of Integrative Biology and Pharmacology at the McGovern Medical School at UT Health. Dr. Cheng is a member of the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the Texas Therapeutics Institute.

Areas of Interest

Research Interests

Our laboratory studies intracellular signaling associated with second messenger cAMP. We apply multidisciplinary approaches, coupling biochemistry, biophysics and cell biology with pharmacology and chemical biology, to understand the structure and function of exchange proteins directly activated by cAMP (EPAC). Our goals are to unravel the signaling intricacies of EPAC proteins and to design pathway specific probes for these important signaling molecules so that their functions can be pharmaceutically exploited and modulated for the treatment of human diseases.

Our laboratory has developed first-in-class EPAC selective inhibitors and EPAC knockout mouse models to study the physiological functions and diseases relevance of this family of important signaling molecules. Recently, we have identified a potential use of EPAC inhibitors in the prevention and treatment of fatal rickettsioses. Currently, we are actively engaged in developing second generation isoform specific EPAC inhibitors and agonists and in exploring their potential uses in various human diseases including cancer, diabetes, chronic pain and infections.

Publications

REFERENCES

  • Tomilin V, Khayyat, NG, Ren G, Zaika O, Khedr S, Staruschenko A, Mei FC, Cheng X, Mamenko M and Pochynyuk O.  (2022).  Deficient regulation of the collecting duct epithelial Na+ channel (ENaC) activity by dietary salt in Epac1-/- and Epac2-/- mice. JCI Insight. 7:e145653.
  • Yang W, Robichaux WG, Mei FC, Lin W, Li L, Pan S, White MA, Chen Y and Cheng X.  (2022).  Epac1 regulates cellular SUMOylation and promotes the formation of SUMO-activating nuclear condensates. Science Advances. 8:eabm2960.
  • Liu H, Mei FC, Yang W, Wang H, Wong E, Toth E, Luo P, Li Y-M, Zhang W* and Cheng X.* (2020). Epac1 inhibition ameliorates pathological angiogenesis through coordinated activation of Notch and suppression of VEGF signaling. Science Advances. 6: eaay3566.
  • Liu W, Ha Y, Xia F, Zhu S, Shi S, Mei FC, Merkley K, Vizzeri G, Motamedi M, Cheng X, Liu H and Zhang W.  (2020).  Neuronal Epac1 mediates retinal neurodegeneration in mouse models of ocular hypertension. J. Exp. Med. 217: pii: e20190930.
  • Robichaux, W. G., Mei, F. C., Yang, W., Wang, H, Sun H, Zhou Z, Milewicz DM, Teng BB and Cheng X.  (2020). Epac1 (Exchange Protein Directly Activated by cAMP 1) Upregulates LOX-1 (Oxidized Low-Density Lipoprotein Receptor 1) to Promote Foam Cell Formation and Atherosclerosis Development. Thromb. Vasc. Biol. 40:e322-e335. doi:  10.1161/ATVBAHA .119.314238.  [ATVB Editor’s Pick]
  • White, MA, Lin W and Cheng X.  (2020).  Discovery of COVID-19 inhibitors targeting the SARS-CoV2 Nsp13 helicase. J Phys Chem Lett. 11:9144-9151. doi: 10.1021/acs.jpclett.0c02421.
  • Barella L, Rossi M, Zhu L, Cui Y, Mei F, Cheng X, Chen W, Gurevich V and Wess J.  (2019).  β cell-intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion. Journal of Clinical Investigation. 130: 3732-3737.
  • Cherezova A, Tomilin V, Buncha V, Zaika O, Ortiz PA, Mei FC, Cheng X, Mamenko M and Pochynyuk O.  (2019).  Urinary concentrating defect in mice lacking Epac1 or Epac2. FASEB J. 33: 2156-2170.
  • Robichaux WG and Cheng X. (2018). Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology and Therapeutics Development. Physiological Reviews. 98:919-1053.
  • Yang W, Mei FC and Cheng X. (2018). EPAC1 regulates endothelial Annexin A2 cell surface translocation and plasminogen activation. FASEB J. 32:2212-2222.
  • Hu Y, Robichaux WG, Kim ER, Mei FC, Wang H, Tong Q, Xu M, Chen J, and Cheng X. (2016). Role of exchange protein directly activated by cAMP isoform 1 in energy homeostasis: regulation of leptin expression and secretion in white adipose tissue. Molecular Cellular Biology. 36:2440-1250. [MCB Spotlight article]
  • Singhmar P, Huo X, Eijkelkamp N, Berciano SR, Baameur F, Mei FC, Zhu Y, Cheng X, Hawke D, Mayor Jr, F, Murga C, Heijnen CJ, and Kavelaars A. ( 2016). A critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1. Proc Acad Natl Sci USA. 113:3036-3041.
  • Ye N, Zhu Y, Chen H, Liu Z, Mei FC, Wild C, Chen H, Cheng X,* and Zhou J.* (2015). Structure-Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-Oxo-N’-Phenyl-Acetohydrazonoyl Cyanide Analogues: Identification of Potent EPAC Antagonists. J Med Chem. 58:6033-6047.
  • Zhu Y, Chen H, Boulton S, Mei F, Ye N, Melacini G, Zhou J*, and Cheng X.* (2015). Biochemical and Pharmacological Characterizations of ESI-09 Based EPAC Inhibitors: Defining the ESI-09 “Therapeutic Window.” Scientific Reports. 5:9344.
  • Almahariq M, Mei FC, Wang H, Cao AT, Yao S, Soong L, Sun J, Cong Y, Chen J, and Cheng X. (2015). Exchange Protein Directly Activated by cAMP (EPAC1) Modulates Regulatory T Cell-Mediated Immune Suppression. Biochem J, 465:295-303.
  • Almahariq M, Chao C, Mei FC, Hellmich MR, Patrikeev I, Motamedi M, and Cheng X. (2015). Pharmacological Inhibition and Genetic Knockdown of EPAC1 Reduce Pancreatic Cancer Metastasis in vivo. Mol Pharm, 87:142-149. [Faculty1000 recommended paper] http://f1000.com/prime/725232154
  • Almahariq M, Mei F, and Cheng X. (2014). cAMP Sensor EPAC Proteins and Energy Homeostasis. Trends Endocrin Metabol, 25(2):60-71.
  • Tao T, Mei F, Agrawal A, Peters CJ, Ksiazek T, Cheng X*, and Tseng C-T.* (2014). Blocking of Exchange Proteins Directly Activated by cAMP (Epac) Leads to Reduced Replication of Middle East Respiratory Syndrome-Coronavirus. J  Virology, 88:3902-10.
  • Almahariq M, Tsalkova T, Mei FC, Chen H, Zhou J, Sastry SK, Schwede F, Cheng X. (2013). A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion. Mol Pharm, 83,122-128.
  • 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.
  • 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. Mol Cell Biol, 33:918-926. [MCB Spotlight and Cover Figure article]
  • 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.
  • Tsalkova T, Mei FC, Li S, Chepurny OG, Liu T, Woods VL Jr, 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, Gribengo AV, and Cheng X. (2011). Exchange protein directly activated by cAMP isoform 2 (Epac2) is not a direct target of sulfonylureas. Assay Drug Develop Tech, 9:88-91. [Faculty1000 selected paper]
  • Li S, Tsalkova T, White MA, Mei FC, Liu T, Wang D, Woods VL Jr*, and Cheng X*. (2011). Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry (DXMS). J Biol Chem, 286:17889-17897. [JBC Paper of the Week, Cover Figure article]