Pharmacology

Warwick, Charles

Charles Warwick

Address: 2-440 BSB
Phone: (319) 353-3887
Email: charles-warwick@uiowa.edu

Mentor: Yuriy Usachev, PhD

Undergraduate Institution: Iowa State University, Ames, IA, BS

Year Entered Into Program: 2012

Affiliations

  • Pharmacology

Research Description

The complement system is a principal component of innate immunity. It consists of more than 30 proteins that are rapidly recruited through a cascade of enzymatic reactions to contribute to host defenses through diverse mechanisms. In spite of growing evidence implicating the complement system in the development of pain hypersensitivity, the underlying mechanisms are still not understood. ¬¬My research focuses on elucidating functions of the complement system in initiating and maintaining chronic pain and to determine the underlying mechanisms. I hypothesize that complement fragments C3a and C5a produce hypersensitivity in pain sensing neurons called nociceptors by facilitating TRPV1 (noxious heat receptor) function via both direct and indirect pathways. The direct pathway involves functional coupling of C3a/C5a receptors with TRPV1 in Dorsal Root Ganglia (DRG) neurons and recruits the PLC-PKC-TRPV1 signaling downstream of C3a/C5a receptor activation. The indirect pathway involves C3a/C5a-dependent activation of immune cells (most likely macrophages), release of NGF, and NGF/TrkA-dependent potentiation of TRPV1. This research will increase our understanding of how the immune system contributes to the pathogenesis of pain triggered by injury or illness. In particular, by exploring previously unrecognized signaling pathways involving C3aR, C5aR, and TRPV1, it will help to identify novel mechanisms that underlie nociceptor sensitization by the complement system and may lead to the development of new analgesics targeting complement fragments and their receptors.