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SUMMARY:Pluripotency\, Etc. - Ihor Lemischka\, Mount Sinai Medical Centre
DTSTART:20120315T130000Z
DTEND:20120315T140000Z
UID:TALK34666@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:One major research interest in our laboratory is focused on un
 derstanding the regulation of stem cell fate decision processes. A second 
 interest is the use of stem cell approaches to develop patient-specific mo
 dels of inherited diseases. Both of these efforts currently involve the us
 e of embryonic or induced pluripotent stem cells (ESC and iPSC\, respectiv
 ely). We have taken a broad\, quantitative systems biology approach to unr
 avel the regulatory mechanisms that are necessary for maintaining and reac
 quiring the self-renewing pluripotent state. Specifically\, we utilize sho
 rt hairpin (sh) RNA techniques to perform loss-of-function perturbations i
 n mouse (m) and human (h) ESC. We have developed a genetic complementation
  strategy to effectively “replace” any gene-product with a version tha
 t can be controlled by a small molecule added to cell cultures. Using this
  approach\, we have perturbed the expression of numerous key regulatory mo
 lecules such as transcription factors\, epigenetic regulators as well as c
 omponents of signaling pathways. After perturbation\, we monitors global m
 olecular changes aver time. These changes include: chromatin modifications
 \, mRNA levels\, microRNA levels and the nuclear proteome. These studies p
 rovide a “real time” view of biological information processing that oc
 curs during and is responsible for a transition in ESC fate. An essential 
 component of our studies is computational biology. This has allowed us to 
 analyze and integrate the large amount of information that is acquired. Co
 mputational analyses have also facilitated the generation of models of how
  regulatory networks function during changing cell fates. We have gained n
 umerous novel insights into ESC regulation. Several of these include: how 
 the Esrrb transcription factor controls pluripotency\, genotoxic stress re
 sponse mechanisms that regulate ESC and translational control as an under-
 appreciated aspect of cell fate regulation. In our second major research f
 ocus\, we have utilized iPSC reprogramming to develop models of human gene
 tic diseases. In particular\, we have developed patient-specific models of
  cardiac disorders and are expanding our efforts to include metabolic dise
 ases. Very recently\, we have used direct programming technologies to dire
 ctly convert mouse fibroblast cells into hemogenic endothelium. This tissu
 e is the origin of hematopoietic stem and progenitor cells during fetal de
 velopment. The programming is fairly efficient and requires four transcrip
 tion factors. An additional exciting feature of these results is our abili
 ty to “kick start” the hemogenic endothelial developmental program\, p
 roviding an in vitro avenue for in-depth analyses. We are currently extend
 ing the direct programming efforts to the human system. \n
LOCATION:Cancer Research UK Cambridge Research Institute\, Lecture Theatre
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