Yang (Kevin) Xiang, Ph.D.

 Yang (Kevin)  Xiang, Ph.D.

Position

  • Professor
  • Pharmacology

Contact

Signaling Transduction, Neurodegenerative Diseases, Heart Failure, Receptor Pharmacology

Research Summary

My current research focuses on insulin resistance associated with aging/stress-related metabolic disorders and diseases such as type 2 diabetes, diabetic cardiomyopathy, and Alzheimer’s disease. We have recently characterized a novel insulin receptor and beta adrenergic receptor network expressed in different tissues. This opens a new field to understand insulin resistance in glucose metabolism as well as in a broad range of cardiovascular and neuronal complications associated with diabetes and metabolic disorders. We were able to draw recent funding from NIH and VA to support research in this exciting new field. One of the major goals is to understand prevalent co-existence of insulin resistance and adrenergic dysregulation in a variety of disease. We utilize a wide range of tools from single molecular analysis of receptor complexes, high resolution of living cell imaging, to in vivo genetic, surgical, and pharmacological manipulation. By combining development of novel analytical tools with in vivo and in vitro characterization of receptor signaling and function, my laboratory has developed an integrative approach to systematically analyze insulin and adrenergic signaling in the brain and peripheral tissues under physiological and disease conditions. We hope to eventually provide information/strategies on clinical therapies for different neuronal and cardiovascular conditions.  

Select Publications

1. Insulin resistance and Alzheimer’s disease.

     In a series studies, we have revealed that the CNS beta2 adrenergic receptor plays an essential role in mediating the cytotoxicity of soluble amyloid beta peptide in the pathogenesis of Alzheimer’s disease. We have shown that amyloid peptide binds to and activates beta2 adrenergic receptor as a partial allosteric agonist, which promotes insulin resistance in brain, and triggers a whole series of signaling cascades for synaptic and neuronal degeneration.

  1. Wisely EV, Xiang YK, Oddo S. (2014) Genetic suppression of β2-adrenergic receptors ameliorates tau pathology in a mouse model of tauopathies. Hum Mol Genet. 23(15):4024-34. PMC4082366.
  2. Wang D, Fu Q, Zhou Y, Xu B, Shi Q, Igwe B, Matt L, Hell JW, Wisely EV, Oddo S, Xiang YK. (2013)  β2 adrenergic receptor, protein kinase A (PKA) and c-Jun N-terminal kinase (JNK) signaling pathways mediate tau pathology in Alzheimer disease models. J Biol Chem. 288(15):10298-307. PMC3624413.
  3. Wang D, Yuen EY, Zhou Y, Yan Z, Xiang YK. (2011) Amyloid beta peptide-(1-42) induces internalization and degradation of beta2 adrenergic receptors in prefrontal cortical neurons. J Biol Chem. 286(36):31852-63. PMCID: PMC3173113.
  4. Wang D, Govindaiah G, Liu R, De Arcangelis V, Cox CL, Xiang YK. (2010) Binding of amyloid beta peptide to beta2 adrenergic receptor induces PKA-dependent AMPA receptor hyperactivity. FASEB J. 24(9):3511-21. PMC2923357.

2. Insulin resistance and cardiac complications in chronic hyperinsulinemia during diabetes.

     We aim to understand the integration and implication of signaling crosstalk under chronic states such as insulin resistance and hyperinsulinemia associated with diabetes. Our data suggests novel intracellular signaling cross talks that shape the beta adrenergic receptor signaling and insulin signaling in different tissues including heart and skeletal muscle, and fat. These novel discoveries offer a new platform to examine the intracellular signaling processes that may contribute to insulin resistance and cardiovascular complication associated with diabetes and aging.

  1. Fu Q, Xu B, Liu Y, Parikh D, Li J, Li Y, Zhang Y, Riehle C, Zhu Y, Rawlings T, Shi Q, Clark RB, Chen X, Abel ED, Xiang YK. (2014) Insulin inhibits cardiac contractility by inducing a Gi-biased β2 adrenergic signaling in hearts. Diabetes. 63:8 2676-2689;  PMC-Pending
  2. Fu Q, Xu B, Parikh D, Cervantes D, Xiang YK. Insulin induces IRS2-dependent and GRK2-mediated β2AR internalization to attenuate βAR signaling in cardiomyocytes. Cell Signal. (2015) 27(3):707-15. PMC-pending.
  3. Liu SB, Li Y, Kim S, Fu Q, Parikh D, Sridhar B, Shi Q, Zhang X, Guan Y, Chen X, Xiang YK. (2012) Activation of the Gs-coupled EP receptor regulates the spatio-propagation of cAMP signal induced by the Gs-coupled βAR in animal hearts. PNAS. 109(17):6578-83. PMC3340097
  4. Zhang X, Szeto C, Gao E, Tang M, Jin J, Fu Q, Makarewich C, Ai X, Li Y, Tang A, Wang J, Gao H, Wang F, Ge X, Kunapuli SP, Zhou L, Zeng C, Xiang YK, Chen X. (2012) Cardiotoxic and Cardioprotective Features of Chronic β-Adrenergic Signaling. Circulation Research, 112(3):498-509 PMC3562387
  5. Cervantes D, Crosby C, and Xiang Y. (2010) Arrestin orchestrates cross-talk between GPCRs to modulate the spatiotemporal activation of ERK MAPK. Circulation Research, 106;79-88, PMC2818802

Affiliations

Biochemistry, Molecular, Cellular and Development Biology

Pharmacology and Toxicology

Honors

2006                                        American Heart Association Scientist Development Award

2009                                        Alzheimer’s Association New Investigator Award

2012                                        American Heart Association Established Investigator Award

2012                                        Shanghai Eastern Scholar