Beavo Lab: Personnel

Current and Recent Members of our PDE Research Group.

Photo of recent lab "reunion". Most people pictured trained in the lab at one time or the other [Note: clearly Ed Krebs and Bill Catterall (lower right) are trainers not trainees :-) ]

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Beavo, Joe

Patrucco, Enrico
Rybalkin, Ira
Rybalkin, Sergei
Shimizu, Masami
Tsai, Lisa
Kraynik, Steve
Hertz, Angie
Parchen, Candace
Heikaus, Clemens

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.

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.

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 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.

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.

Heiko Poppe
Visiting Student - Current Research Interests: Selectivity of various analogs of cAMP and cGMP on different isozymes of cyclic nucleotide phosphodiesterases. I am looking into the use of a new method of measuring PDE activity using a microcalorimeter. This method does not require radiolabeled substrate and is therefore potentially very useful for measuring hydrolytic rates of modified version of cAMP and cGMP. I am currently back in school in Germany.

Enrico Patrucco
Postdoctoral Fellow - Current Research Interests: Regulation of PDE7 and 8. I am particularly interested in determining the roles of these PDEs in cardiac function. My preliminary data suggest that PDE8 in particular will be a very important regulator of cardiac function. Stay tuned..

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

Sergei Rybalkin
Res Asst Professor - Current Research Interests: cAMP and cGMP play an important role in regulating the contractility of smooth muscle cells (SMCs). Cyclic nucleotides also act as antiproliferative agents in these cells. My more recent efforts have been directed towards the roles of PDE5 and also selective inhibitors of PDE5 on fibrosis and repair.

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.

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	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.
	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.
	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 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.
	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.
	Heiko Poppe Visiting Student - Current Research Interests: Selectivity of various analogs of cAMP and cGMP on different isozymes of cyclic nucleotide phosphodiesterases. I am looking into the use of a new method of measuring PDE activity using a microcalorimeter. This method does not require radiolabeled substrate and is therefore potentially very useful for measuring hydrolytic rates of modified version of cAMP and cGMP. I am currently back in school in Germany.
	Enrico Patrucco Postdoctoral Fellow - Current Research Interests: Regulation of PDE7 and 8. I am particularly interested in determining the roles of these PDEs in cardiac function. My preliminary data suggest that PDE8 in particular will be a very important regulator of cardiac function. Stay tuned..
	Irina Rybalkina Research Technician - Current Research Interests: Structure/function relationships among different selective inhibitors of phosphodiesterases.
	Sergei Rybalkin Res Asst Professor - Current Research Interests: cAMP and cGMP play an important role in regulating the contractility of smooth muscle cells (SMCs). Cyclic nucleotides also act as antiproliferative agents in these cells. My more recent efforts have been directed towards the roles of PDE5 and also selective inhibitors of PDE5 on fibrosis and repair.
	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.