Research Interests

Molecular mechanisms underlying diabetes, heart failure, and Alzheimer's disease

My current research focuses on aging/stress-related metabolic and inflammatory disorders and diseases like type 2 diabetes, diabetic cardiomyopathy, heart failure, and Alzheimer’s disease. We have characterized a novel insulin receptor and beta-adrenoceptor network expressed in different tissues. This discovery opens a new field to understand insulin resistance in glucose metabolism and a broad range of cardiovascular and neuronal complications. We drew recent funding from NIH and VA to support these research directions. One of the major goals is to understand the prevalent co-existence of insulin resistance and sympathetic adrenergic dysregulation in the CNS and peripheral tissues. We apply a wide range of tools from single molecular analysis of receptor complex and high resolution of living cell imaging to in vivo genetic, surgical, and pharmacological manipulation. My laboratory has developed an integrative approach to systematically analyze insulin and adrenergic signaling in the brain and peripheral tissues. Eventually, we hope to 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
• Neuroscience

Specialties / Focus

• Behavioral Physiology
• Biochemistry
• Cardiorespiratory Physiology
• Cell Biology
• Cellular Physiology
• Molecular Medicine
• Molecular Physiology
• Molecular Physiology
• Neurobiology
• Neurophysiology
• Signal Transduction
• Stem Cell Biology

Courses

• MCP MCP210C Advanced Physiology, Spring

Professional Societies

• ASBMB
• ASPET
• ADA
• AHA
• ASCB

Degrees

• 2000 Ph.D. Cell and Developmental Biology Oregon Health Science University

Publications

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

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

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

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.

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. Proc. Natl. Acad. Sci. U.S.A. 109(17):6578-83

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. Mar 27. [Epub ahead of print]

Barbagallo F, Xu B, Reddy GR, West T, Wang Q, Fu Q, Li M, Shi Q, Ginsburg KS, Ferrier W, Isidori AM, Naro F, Patel HH, Bossuyt J, Bers D,Xiang YK. Genetically Encoded Biosensors Reveal PKA Hyperphosphorylation on the Myofilaments in Rabbit Heart Failure. 2016 Circ Res. 119(8):931-43.

Mittal S, Bjørnevik K, Im DS, Flierl A, Dong X, Abo KM, Long L, Jin M, Xu B, Xiang YK, Rochet J-C, Engeland A, Rizzu P, Heutink P, Bartels T, Selkoe DJ, Caldarone BJ, Glicksman MA, Khurana V, Schüle B, Park DS, Riise T and Scherzer CR. Beta-Adrenoreceptor Ligands Regulate Endogenous a-Synuclein Expression and Risk of Parkinson’s Disease. 2017 Science, Sep 1;357(6354):891-898

Wang Q, Liu Y, Fu Q, Xu B, Zhang Y, Kim S, Tan R, Barbagallo F, West T, Anderson E, Wei W, Abel ED, Xiang YK. Inhibiting insulin-mediated β2AR activation prevents diabetes-associated cardiac dysfunction. 2017 Circulation. 135(1):73-88.

Shen A, Nieves-Cintron M, Deng Y, Shi Q, Chowdhury D, Qi J, Hell JW, Navedo MF, and Xiang YK. Functionally distinct and selectively phosphorylated subpopulations of a GPCR co-exist in a single cell. 2018 Nature Comm Mar 13;9(1):1050. doi: 10.1038/s41467-018-03459-7.

Maeder CI, Kim JI, Liang X, Kaganovsky K, Shen A, Li Q, Li Z, Wang S, Xu XZS, Li JB, Xiang YK, Ding JB, Shen K. The THO Complex Coordinates Transcripts for Synapse Development and Dopamine Neuron Survival. 2018 Cell. Sep 6;174(6):1436-1449.e20.

Shen A, Chen D, Kaur M, Bartels P, Xu B, Shi Q, Martinez JM, Man KM, Nieves-Cintron M, Hell JW, Navedo MF, Yu X, Xiang YK. β-blockers augment L-type Ca2+ channel activity by targeting spatially restricted β2AR signaling in neurons. Elife. 2019 Oct 14;8. pii: e49464.

Xu B, Li M, Wang Y, Zhao M, Morotti S, Shi Q, Wang Q, Barbagallo F, Teoh JP, Raghavender Reddy G, Bayne EF, Liu Y, Shen A, Puglisi JL, Ge Y, Li J, Grandi E, Nieves-Cintrón M, Xiang YK. GRK5 Controls SAP97-Dependent Cardiotoxic β1 Adrenergic Receptor-CaMKII Signaling in Heart Failure. Circ Res. 2020 Aug 28;127(6):796-810

Wang Y, Shi Q, Li M, Zhao M, Raghavender Reddy G, Teoh JP, Xu B, Zhu C, Ireton KE, Srinivasan S, Chen SL, Gasser PJ, Bossuyt J, Hell JW, Bers DM, Xiang YK. Intracellular β1-Adrenergic Receptors and Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation to Enhance Cardiac Contractility. Circ Res. 2021 Jan 22;128(2):246-261.

Wang Y, Zhao M, Shi Q, Xu B, Zhu C, Li M, Mir V, Bers DM, and Xiang YK. Monoamine Oxidases Desensitize Intracellular β1AR Signaling in Heart Failure. Circ Res. 2021 Oct 29;129(10):965-967.