BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Pain and swelling\, suffering and love: the NGF story - Dr. Geoff 
 Woods\, Department of Genetics\, Cambridge
DTSTART:20090929T090000Z
DTEND:20090929T093000Z
UID:TALK18684@talks.cam.ac.uk
CONTACT:Hannah Critchlow
DESCRIPTION:This talk is part of the Cambridge Clinical Neuroscience and M
 ental Health Symposium\, 29th - 30th September 2009 at West Road Concert H
 all. This event is free to attend for cambridge neuroscientists although r
 egistration is required. To register\, and for further information\, pleas
 e visit: http://www.neuroscience.cam.ac.uk/cnmhs/\n\nAbstract: We study ra
 re individuals who feel no pain. My presentation describes a homozygous mi
 s-sense mutation in Nerve Growth Factor gene in such a family. The phenoty
 pe is different from the only other report in the literature. The phenotyp
 e (unsurprisingly) is identical to that of TRKA mutations\; TRKA is the re
 ceptor for NGF on pain sensing neurons. Our functional studies have assess
 ed the ability of both our and the previous mutation to induce neuron diff
 erentiation using a PC12 model. This was used as NGF is a known inductor o
 f neuronal differentiation in this cell line. Our mutation was a null. We 
 have also assessed the trafficking and excretion of our NGF mutation. The 
 mutation affects the N-terminal domain of the secreted NGF-Beta protein. H
 owever\, we have found that it is NGF cleavage to form the NGF-Beta that i
 s deficient. Finally we have observed an immune phenotype in our patients 
 - which may have been expected given the role of NGF-Beta in inflammation.
  As NGF-Beta also causes hyper-excitability to pain sensing neurons it exp
 lains why infective lesions swell and are painful\, and the rational for d
 eveloping NGF-Beta blockers are analgesics. Our work suggests that such dr
 ugs should be used with caution as they may cause immune-deficiency.\n\nRe
 ferences: \n\nNilsen KB\, et al. Two novel SCN9A mutations causing insensi
 tivity to pain. Pain. 2009 May\;143(1-2):155-8.\n\nCox JJ\, et al. An SCN9
 A channelopathy causes congenital inability to experience pain. Nature. 20
 06 Dec 14\;444(7121):894-8.\n\nBiosketch: I am a Paediatrician who changed
  to a Clinical Geneticist as they were more involved in the cause of menta
 l retardation than in its treatment. I still see myself as a Paediatrician
  however. Along the way I have worked in Vancouver\, Melbourne and Oxford 
 in my training phase\, and Leeds as a consultant where I began to be inter
 ested in clinically led research. I moved to Cambridge in 2005 and have a 
 research team dedicated to finding genes that cause Mendelian diseases - t
 hat is where a gene change\, alone and always\, causes a significant human
  phenotype change. Clinically my main interest is diseases that stop the h
 uman brain growing to its potential enormous size\; viewed from an evoluti
 onary point of view!. The common mechanism appears to be dysfunction of th
 e centrosome somewhat surprisingly. We also have a significant interest in
  finding genes that control pain sensing in humans and in understanding ho
 w disease mutations then cause human disease phenotypes - which is never a
 s straight forward as it should be!\n \n\n
LOCATION:West Road Concert Hall
END:VEVENT
END:VCALENDAR