Xiang, Kevin Y.

Department of Molecular and Integrative Pysiology
Ph.D. (2000) Oregon Health Sciences University

    Research Topics

• Signaling transduction in mammalian cardiac muscle cells
• Synapse formation and function between neuron and cardiac muscle
• GPCR signaling in alzheimer disease

   Research Interests

    Research in my lab focuses on the functions of a family of GPCRs (adrenergic receptors) in two areas: heart contraction and Alzheimer disease. GPCRs are nature's most versatile biological sensors. They conduct the majority of transmembrane responses to hormones and neurotransmitters, and mediate the senses of pressure, sight, smell, and taste. Adrenergic receptors, which transmit signals in both central and peripheral nerve systems, are one of the most extensively characterized subfamilies of GPCRs and serve as a model system for understanding the structure, cell biology and physiology of GPCRs. We are investigating adrenergic receptors using in vitro and in vivo systems to determine the structural and cellular basis for more complex functional properties that are only observed in differentiated cells.

We have utilized strains of knockout mice for three beta (β) adrenergic receptor subtypes. These mice have provided insight into the physiologic role of specific receptor sybtypes in vivo. From sutdies of β adrenergic receptor knockout mice we found that β1 and β2 adrenergic receptors play untique roles in regulating cardiovascular function, and are associated with heart failure development. We are using neonatal myocytes, sympathetic ganglia neurons from β1/ β2 adrenergic receptors double knockout mice as a differentiated expression system to study the structural and cellular basis for differences in the funtional properties of these two receptors. Our studies suggest that functional differences between β1 and β2 adrenergic recptors are due to their localization on post-synaptic cardiac myocyte cell surface relative to synapse formation between sympathetic neurons and cardiac myocytes.

In another project, we have found that amyloid Aβ peptide directly activates βAR in vitro assays. Aβ can activate β1AR receptor in glia astrocytes to induce cAMP accumulation. We are expanding this new project to find out how cellular and function role of Aβ induced βAR signaling in glia and neuron, and its role in Alzheimer disease.

Our current reasearch focuses on four different areas:

1. Characterize the signaling complexes associated with β1 and β2 adrenergic receptors in cardiac myocytes, and structural basis for the association under distinct agonist simulation

2. Regulation of cAMP/PKA pathways by receptor activations and phosphodiesterases. We will use live-imaging studies on the individual subcellular events (i.e. cAMP, PKA, and Ca ²⁺ signaling)during activation of the receptors and their significance in myocyte contraction and myocyte apoptosis.

3. Adrenergic synaptic regulation of β1 and β2 adrengergic receptor cellular and signaling properties within the model system of co-culturing sympathetic neurons and cardiac myocytes. We will try to understand formation of neuron/muscular synaptic formation, and its influence on the adrenergic receptor function.

4. Adrenergic receptor signaling in Alzheimer disease. We are going to examine the receptor signaling induced by amyloid Aβ peptide in glia and neurons. We try to determine whether the receptor signaling is invovled in the disease progress.

These studies will hep us understand the signaling properties of the receptors in cellular levels, and may provide new approaches to intervene the receptor funtions in variety of clinical conditions such as heart failure and hypertension, as well asAlzheimer diesease.

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