University of Washington
Department of Pharmacology
Beavo Cyclic Nucleotide Regulator Signal Transducer





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Current and Recent Members of our PDE Research Group
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Beavo, Joe

Rybalkin, Sergei
Hinds, Tom
Shimizu, Masami
Rybalkina, Irina
Zhang, Xiaoying
Tsai, Lisa
Kraynik, Steve
Hertz, Angie
Parchen, Candace
Beltejar,  Claude
Nangle, Shannon



Joe Joe Beavo

Professor - Joe's graduate training was with Earl Sutherland and Joel Hardman at Vanderbilt University. He moved on to do postdoctoral work with Ed Krebs at UC Davis and eventually moved to the University of Washington as an Asst Professor.

Current Research Interests: Regulation and function of cyclic nucleotide phosphodiesterases.  Cyclic nucelotides regulate many signaling pathways in tissues throughout the body.  Our research group studies phosphodiesterases (PDEs), the enzymes that break down cyclic nucleotides.  Regulation of PDE function can cause dynamic changes in cyclic nucleotide levels in cells.  One group in the lab focuses on determining the physiological roles of each PDE in the tissues where it is expressed.  Another group has interests in determining the crystal and NMR structures of the various domains of the PDE and how these structures relate to function and regulation. For specific examples of the types of projects we work on, please see the short descriptions of student research below.

CV of Joseph Beavo
Sergei Sergei Rybalkin

Res. Ass. Professor - Current Research Interests - Cyclic nucleotides mediated modulation of myocardial and smooth muscle responses. Molecular and physiological mechanisms of regulation of cGMP-hydrolyzing phosphodiesterases, PDE1s and PDE5, in the cardiovascular and immune systems.
Tom Tom Hinds

Description Coming Soon
Masami Masami Shimizu

Postdoctoral Fellow - Current Research Interests: I just returned to the lab recently after a 3 year leave to be at home with my new son, Stephen. I am interested in the roles of PDEs in liver function and also in olfaction. I am also interested in utilizing immunocytochemical localization as a tool to determine what physiological functions are played by different PDEs in a particular cell type of a tissue.
Ira Irina Rybalkina

Research Technician - Current Research Interests: Structure/function relationships among different selective inhibitors of phosphodiesterases.
Xiaoying
Xiaoying Zhang

Postdoctoral Fellow- Current research interests: the role of PDE8A in M-CSF dependent macrophage differentiation and activation. PDE8A inhibitor and PDE8A knock-out mice have been used in this study. My recent data suggest PDE8A inhibition might exert pro-inflammatory effects on M-CSF dependent macrophage differentiation and activation. The mechanisms of this pro-inflammatory effect may be of clinical importance. Tumor associated macrophages, which have anti-inflammatory characteristics, have been implicated in promoting disease progression. The conversion of these macrophages, by PDE8A inhibitor treatment, to a more inflammatory phenotype may be one step towards reducing pro-cancerous factors in the tumor microenvironment.
Lisa Lisa Tsai

Graduate Student - Current research interests; Roles of PDE8s in Steroidogenesis. We have recently shown that one specific isozyme of PDE, PDE8A, is an important regulator of LH induced testosterone regulation in Leydig cells. My current project is to determine if a similar regulatory mechanism is also present for corticosterone production by adrenal fasiculata cells. I am ustilizing both selective inhibitors of PDEs as well as animals having the PDE8 genes knocked out as tools to address this problem. I am also interested in utilizing fluoresence resonance energy transfer (FRET) as a means of visualizing and measuring cAMP in intact cells.
Steve Steve Kraynik

Graduate Student - Current Research Interests: I am currently developing the methods to test the hypothesis that PDE8 is a regulator of lipolysis by isolated brown fat cells. I am also interested in looking at the roles of this PDE in fat cell differentiation. My preliminary studies suggest that PDE8 may be a particularly important regulator of brown fat metabolism.
Angie Angie Hertz

Graduate Student - Current Research Interests; I am studying the role(s) of cAMP and PDEs in the control of monocyte differentiation into macrophages. Recent array data suggests that cAMP increases due to PDE4 inhibition can have a PROinflammatory effect in this cell system. Much of this is dues to increased chemokine secretion. As this has rather major implications for the use of PDE4 inhibitors as anti-inflammatory agents my current work is focused on determining in two different mouse models if addition of a chemokine antagonist to a PDE4 inhibitor will increase the efficacy of the PDE4 inhibitor in vivo. The current model is a high fat diet induced insulin resistance model. Since inflammation is a major aspect of control of insulin sensitivity, we expect this model to be a good one for adult onset diabetes.
Candace Candace Parchen

Graduate Student - Current Research Interests; Roles of PDE5 effects on dystrophic cardiac muscle. I am interested in how cGMP and selective inhibitors of PDE5 regulate cardiac muscle hypertrophy. Our most recent data strongly suggests that treatment of dystrophic mice with sildenafil will prevent and even reverse the negative cardiac impairment seen in the dystrophic mouse. I use a number of non-invasive methods for monitoring heart function including echocardiography.
Claude Claude Beltejar

Graduate Student - Current Research Interests: The use of phosphodiesterase inhibitors as cancer therapeutics. I'm interested in the cyclic nucleotide signaling regulation of myeloid derived suppressor cells.  In the tumor microenviornment , these cells may promote tumor progression by preventing the immune system from eliminating cancerous cells.  Molecules that interupt cyclic nucleotide signaling involved in promoting this immune suppresive phenotype could be utilized as therapeutics.
Shannon Shannon Nangle

Description Coming Soon.