Department of Pharmacology, School of Medicine
Molecular mechanisms underlying diabetes, heart failure, and Alzheimer's disease
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 complications associated with diabetes and metabolic disorders. We were able to draw recent funding from NIH and VA to support 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 metabolic and cardiovascular conditions.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Molecular, Cellular and Integrative Physiology
Specialties / Focus
- Behavioral Physiology
- Cardiorespiratory Physiology
- Cell Biology
- Cellular Physiology
- Molecular Medicine
- Molecular Physiology
- Molecular Physiology
- Signal Transduction
- Stem Cell Biology
- MCP MCP210C Advanced Physiology, Spring
- 2000 Ph.D. Cell and Developmental Biology Oregon Health Science University
Diabetes and cardiovascular complication
Soto D, De Arcangelis V, Zhang J and Xiang Y (2009) Dynamic PKA activities induced by beta adrenoceptors dictate signaling propagation for substrate phosphorylation and myocyte contraction, Circulation Research. 27; 104(6): 770-9.
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
Chakir K, Depry C, Dimaano VL, Zhu WZ, Vanderheyden M, Bartunek J, Abraham TP, Tomaselli GF, Liu SB, Xiang YK, Zhang M, Takimoto E, Dulin N, Xiao RP, Zhang J, Kass DA. (2011) Gαs-Biased β2-Adrenergic Signaling from Restoring Synchronous Contraction in the Failing Heart. Science Translational Medicine. 14;3(100):100ra88
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.
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. (2013) Cardiotoxic and Cardioprotective Features of Chronic β-Adrenergic Signaling. Circulation Research, 112(3):498-509 Alzheimer's disease
Wang D, Govindaiah, Liu R, Skarpiak B, De Arcangelis V, Cox CL, Xiang YK. (2010) Amyloid β dimer activates β2 adrenergic receptor and induces PKA dependent AMPA receptor hyperactivity. FASEB J 24(9):3511-21
Wang D, Yuen EY, Zhou Y, Yan Z and Xiang YK. (2011) Amyloid β induce internalization and degradation of β2 adrenergic receptor in prefrontal cortical neurons. J. Biol. Chem. 286(36):31852-63
Wang D, Fu Q, Zhou Y, Xu X, Shi Q, Igwe B, Matt L, Hell HW, Wisely EV, Oddo S, Xiang YK. (2013) β2 adrenergic receptor, PKA and JNK signaling pathways mediate tau pathology in Alzheimer’s disease models. J. Biol. Chem. (Published online) Single Molecular Studies
Yum K, Yu MF, Wang N and Xiang YK (2010) Bio-functionalized nanoneedles for the direct and site-selective delivery of probes into living cells. BBA General. 1810(3):330-8
Jain A, Liu R, Ramani B, Arauz E, Ishitsuka Y, Ragunathan K, Park J, Chen J, Xiang YK*, and Ha J*. (2011) Probing Cellular Protein Complexes via Single Molecule Pull-down. Nature 473(7348):484-8, * co-corresponding author.
Jain A, Liu R, Xiang YK*, and Ha J*. (2012) Single molecular Pull-down for studying protein interactions. Nature Protocol. 7: 445–452, * co-corresponding author.