I have spent the last 17 years investigating the cellular and molecular mechanisms by which general anesthetic agents interact with and activate PKC isoforms in cardiac muscle cells to alter Ca2+ signaling and inotropic signal transduction pathways important for the regulation and modulation of myocardial contractility. Over the past 4 years, I have extended my studies of anesthetic actions on cardiomyocyte Ca2+ and contractility, to anesthetic interactions with the TRP receptor cation channel family in dorsal root ganglion sensory neurons and signaling pathways important for cross-talk between these channels. Recently, TRPV1 and TRPA1 receptors have emerged as key players in sensing tissue damage and contribute to numerous pathophysiological and chronic pain syndromes. In addition, several pungent general anesthetic agents have been shown to activate and/or sensitize TRP receptors, thereby enhancing post-surgical pain and inflammation associated with tissue injury. The long-term research objective of my laboratory is to elucidate the cellular and molecular mechanisms regulating TRP channel function (sensitization, desensitization, re-sensitization), the importance of cross-talk between TRP channels in nociceptor function and the signaling pathways and mechanisms associated with TRP channel cross-talk, as well as defining the molecular interactions between anesthetic agents and TRP channels. The physiology of nociceptive neurons and cross-talk between TRPA1 and TRPV1 receptors lay at the core of understanding peripheral hypersensitivity and chronic pain syndromes. Such information is vital to the design and synthesis of novel analgesic agents that can directly target these TRP channels – defining a new and logical strategy in pain relief. I have a broad background in cellular signal transduction and anesthetic actions on signaling pathways regulating Ca2+ in electrically excitable cells, which is absolutely necessary for the challenging projects I have planned for the future in sensory neurons.
Scholarly, Creative & Professional Activities
1. Wickley P, Shiga TS, Murray PA, Damron, DS. Propofol modulates Na+-Ca2+ exchange via protein kinase C in diabetic cardiomyocytes. Anesthesiology 106:302-11, 2007.
2. Wickley PJ, Yuge R, Martin BA, Mayer JC, Damron DS. Propofol allosterically modulates and activates recombinant PKCe. Anesthesiology 111:36-43, 2009.
3. Wickley PJ, Yuge R, Russell MS, Zhang H, Sulak MA, Damron DS. Propofol modulates agonist-induced transient receptor potential vanilloid subtype-1 receptor desensitization via a protein kinase Ce-dependent pathway in mouse dorsal root ganglion sensory neurons. Anesthesiology 113: 833-44, 2010.
4. Zhang H, Wickley PJ, Sinha S, Bratz, IN, Damron DS. Propofol restores transient receptor potential vanilloid receptor subtype-1 sensitivity via activation of transient receptor potential ankyrin receptor subtype-1 in sensory neurons. Anesthesiology 114:1169-79, 2011.
5. Ohanyan V, Guarini G, Thodeti C, Talasila P, Raman P, Haney R, Meszaros J, Damron DS, Bratz I. Endothelin mediated in vivo pressor responses following TRPV1 activation. Am. J. Physiol. Heart 301:1135-42, 2011
Ongoing Research Support
Title: Propofol and Protein Kinase C: Molecular Interactions in Cardiomyocytes
Type: RO1 HL65701-09 (competitive renewal) Derek S. Damron (PI) Period: 07/01/2007–06/30/2012
The major goal of the project is to identify the cellular signaling pathways by which the intravenous anesthetic, propofol, acts as a ligand to activate PKCe, and to delineate the molecular mechanism by which interaction and activation with the enzyme occurs.
Pending Research Support
Title: Propofol and TRP Channels: Mechanisms of Regulation and Interaction
Type RO1 NS078243-01 Derek S. Damron (PI) Period: 06/012012-05/31/2017
The major goal of the project is to delineate the molecular mechanism by which the intravenous anesthetic agent, propofol, acts as a ligand to activate TRPA1 channels in sensory neurons, and elucidate the cellular signaling pathways by which TRPA1 activation modulates TRPV1 sensitivity to agonist stimulation.
- Anesthetic Agents
- Myocardial Contractility
- Vascular Regulation
- Pain Signaling
OFFICEDepartment of Biological Sciences
Kent State University
CONTACT INFOPhone: 330-672-3370
COURSES TEACHINGSpring 2014
- BSCI 80198 - 016 Research
- BSCI 40196 - 033 Individual Investigation
- BMS 60198 - 002 Research
- BSCI 80198 - 004 Research
- BSCI 80199 - 022 Dissertation I
- BSCI 50143 - 001 Eukaryotic Cell Biology
- BSCI 60144 - 001 Sel Read Eukaryotic Cell
- BSCI 70143 - 001 Eukaryotic Cell Biology
- BSCI 70144 - 001 Sel Read Eukaryotic Cell