BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4//
BEGIN:VEVENT
UID:20251108T083141EST-9481LIRl02@132.216.98.100
DTSTAMP:20251108T133141Z
DESCRIPTION:The Killam Seminar Series presents Tackling sporadic ALS-FTD th
 rough TDP-43 knockin models.\n\nThe seminar will be taking placed in perso
 n at The Neuro (Jeanne Timmins Ampitheatre)\n\nTo attend in person\, regis
 ter here\n\nTo attend virtually\, register here.\n\nSpeaker: Jemeen Sreedh
 aran\, MD\, PhD\n\nNeurologist\, King's College London\, UK\n\nAbstract: A
 LS is a largely sporadic motor neuron disease without cure. 97% of cases d
 emonstrate cytoplasmic aggregation and nuclear depletion of the RNA bindin
 g protein TDP-43. Mutations in TARDBP\, the gene encoding TDP-43\, account
  for only ~1% of all ALS cases but offer an opportunity to understand the 
 mechanisms underlying disease. Most TDP-43 studies have focussed on transg
 enic overexpression of TDP-43 to recapitulate histopathological hallmarks 
 of disease\, but these models may demonstrate artefacts of transgenesis. W
 e have used CRISPR to generate disease models more reflective of the human
  condition at the genetic level. We have discovered that Tardbp mutation c
 an disturb TDP-43 autoregulation in mice\, causing cognitive rather than m
 otor phenotypes. TARDBP mutation can also disturb autoregulation in human 
 cells. We have been working to develop the TDP-43(Q331K) knock-in mouse as
  a translational tool using in vivo 9.4T MRI to guide molecular studies. O
 ur iPSC tools are currently being used to better understand the mechanisms
  of TDP-43 autoregulation and to develop platforms for genetic and small-m
 olecule regulators of TDP-43 expression. We are only scratching the surfac
 e in these preliminary studies and a more extensive characterisation of TA
 RDBP mutations using knock-in approaches may be of great value.\n\nBio: I 
 am a neurologist with a research interest in TDP-43\, a DNA/RNA-binding pr
 otein that is dysregulated in motor neuron disease and dementia including 
 frontotemporal dementia and Alzheimer's disease. TDP-43 levels in the brai
 n are exquisitely regulated in health by autoregulation\, but this mechani
 sm is disturbed in disease. My laboratory has developed human cellular and
  mouse model systems to understand autoregulation with a view to normalisi
 ng TDP-43 expression for therapeutic gain. We use genetic engineering tech
 nologies to create more realistic models of disease than ever before. We a
 lso aim to understand the structural\, functional and molecular effects of
  TDP-43 misregulation on brain development\, as age-related neurodegenerat
 ive diseases probably start much earlier in life than previously thought. 
 In 2019 I received the Alzheimer’s Research UK David Hague Early Career In
 vestigator Award. My other roles include being module 3 lead for the MSc i
 n Clinical Neuroscience and teaching medical students clinical neurology.
 \n\n\nSupported by the generosity of the Killam Trusts \, The Neuro’s Kill
 am Seminar series hosts outstanding guest speakers.\n
DTSTART:20220524T200000Z
DTEND:20220524T210000Z
SUMMARY:Killam Seminar Series: Tackling sporadic ALS-FTD through TDP-43 kno
 ckin models
URL:/neuro/channels/event/killam-seminar-series-tackli
 ng-sporadic-als-ftd-through-tdp-43-knockin-models-339533
END:VEVENT
END:VCALENDAR