Korean American <br>Bio Industry Council
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제211회 NEBS Monthly Meeting

  • 23 Feb 2012
  • 6:30 PM - 9:00 PM
  • Center for Life Science (CLS) building (12th floor), 3 blackfan Circle, Boston, MA 02115

제211회 NEBS Monthly Meeting

일시: 2012년 2월 23일 (목요일) 6:30 pm
장소: Center for Life Science (CLS) building
        12th floor
        3 blackfan Circle, Boston, MA 02115

Seminar 1:


IDH1 Mutations and Adult Brain Tumors: Transformation by the R Enantiomer of 2-HG Linked to EglN Activation


Sungwoo Lee, Ph.D.

Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School


The identification of succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) mutations in human cancers has rekindled the idea that altered cellular metabolism can transform cells. Inactivating SDH and FH mutations cause the accumulation of succinate and fumarate, respectively, which can inhibit 2-oxoglutarate (2-OG)-dependent enzymes, including the EGLN prolyl 4-hydroxylases that mark the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. Inappropriate HIF activation is suspected of contributing to the pathogenesis of SDH-defective and FH-defective tumours but can suppress tumour growth in some other contexts. IDH1 and IDH2, which catalyse the interconversion of isocitrate and 2-OG, are frequently mutated in human brain tumours and leukaemias. The resulting mutants have the neomorphic ability to convert 2-OG to the (R)-enantiomer of 2-hydroxyglutarate ((R)-2HG). Here we show that (R)-2HG, but not (S)-2HG, stimulates EGLN activity, leading to diminished HIF levels, which enhances the proliferation and soft agar growth of human astrocytes. These findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumors promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.



Seminar 2:


In search of the fear engram


Jun-Hyeong Cho, Ph.D., Postdoctoral Research Associate

Vadim Bolshakov Laboratory, Department of Psychiatry, McLean Hospital, Harvard Medical School


My talk will consist of two parts.  In the first part, I will review the neurobiology of the amygdala in relation to classical fear conditioning.  The amygdala is a subcortical brain area essential for the acquisition and expression of innate and leaned fear.  Abnormal function of the amygdala has been implicated in the development of anxiety disorders including posttraumatic stress disorder and phobia.  For studying the neuronal basis of these psychiatric disorders, researchers have used auditory fear conditioning, where subjects learn the association of a neutral conditioned stimulus (tone) with an aversive unconditioned stimulus (shock).  During fear conditioning, fear memory trace is encoded in the amygdala, where signals from both conditioned and unconditioned stimuli are integrated.


In the second part of my talk, I will present synaptic mechanism of auditory fear conditioning.  The acquisition of fear memory is thought to be mediated by synaptic plasticity (experience-dependent changes in synaptic strength) in the amygdala.  We recently reported a new form of synaptic plasticity termed input-timing-dependent plasticity (ITDP), which depends on the timing of the activation of two convergent inputs to the amygdala (Cho et al., Nat Neurosci, 15, 113–122).  Mechanistically, ITDP in the amygdala requires calcium release from the internal stores through IP3 receptors and calcium influx through calcium-permeable kainate receptors.  Moreover, our results suggest that ITDP in the amygdala may contribute to encoding fear memory during auditory fear conditioning.  I will discuss these results focusing on the mechanism of ITDP and its implication in the acquisition of conditioned fear memory.

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