I am principally interested in the reaction of the peripheral nervous system, and second order neurons of the spinal dorsal horn to axonal damage, whether these changes result in maladaptive phenotypes (chronic pain) (Costigan et al., 2009a)or adaptive ones (regeneration) (Richardson et al., 2009). My focus is developing and using truly unbiased genetic research tools to obtain an unprecedented view of these mechanisms.
From these data we wish to glean key genes and functional cascades, in order that these mechanisms can be proven in the laboratory, always with a view to translate such knowledge into future therapies.
To do this I use whole genome expression microarrays in rodents with Dr Griffin (MGH), Dr’s Moss & Fitzgerald (London, UK), and Dr’s Coppola & Geschwind (UCLA). I use genome wide SNP arrays in humans, in collaboration with Dr’s Belfer & Lariviere (Pittsburgh), as well as Dr Diatchenko (UNC). I work with Dr’s Neely & Penninger (Vienna, Austria) to search drosophila genetics for relevant phenotypes (Neely et al., 2010).
All of these data are combined to produce strong leads which are analyzed by multiple molecular methods prior to target development in humans.
Examples of such work include,
1.The identification and subsequent characterization of GTP Cyclohydrolase 1 (GCH1) as a determinant of pain sensitivity in rodents (Tegeder et al., 2006).
Current work develops cutting edge transgenic animals to further investigate the tetrahydrobiopterin pathway in sensory neurons as well as defining other human pain targets (Costigan et al., 2010).
2.The identification and characterization of the role of the innate (Griffin et al., 2007)and the adaptive immune system (Costigan et al., 2009b)in neuropathic pain. Current work develops an understanding of how T-lymphocytes and myeloid cells interact to create neuropathic pain.
3. I am actively exploring the mechanisms of regeneration within peripheral nervous system (Mills et al., 2007) and am currently working up multiple exciting new genetic leads in this area.