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(Hoffmann Johann)
10 results
  • Drugging an undruggable pocket on KRAS. [Journal Article]
    Proc Natl Acad Sci U S A 2019; 116(32):15823-15829Kessler D, Gmachl M, … McConnell DB
  • The 3 human RAS genes, KRAS, NRAS, and HRAS, encode 4 different RAS proteins which belong to the protein family of small GTPases that function as binary molecular switches involved in cell signaling. Activating mutations in RAS are among the most common oncogenic drivers in human cancers, with KRAS being the most frequently mutated oncogene. Although KRAS is an excellent drug discovery target for…
  • Limbic-motor integration by neural excitations and inhibitions in the nucleus accumbens. [Journal Article]
    J Neurophysiol 2017; 118(5):2549-2567Morrison SE, McGinty VB, … Nicola SM
  • The nucleus accumbens (NAc) has often been described as a "limbic-motor interface," implying that the NAc integrates the value of expected rewards with the motor planning required to obtain them. However, there is little direct evidence that the signaling of individual NAc neurons combines information about predicted reward and behavioral response. We report that cue-evoked neural responses in th…
  • Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat. [Journal Article]
    Elife 2017; 6Harony-Nicolas H, Kay M, … Buxbaum JD
  • Mutations in the synaptic gene SHANK3 lead to a neurodevelopmental disorder known as Phelan-McDermid syndrome (PMS). PMS is a relatively common monogenic and highly penetrant cause of autism spectrum disorder (ASD) and intellectual disability (ID), and frequently presents with attention deficits. The underlying neurobiology of PMS is not fully known and pharmacological treatments for core symptom…
  • Dopamine invigorates reward seeking by promoting cue-evoked excitation in the nucleus accumbens. [Journal Article]
    J Neurosci 2014; 34(43):14349-64du Hoffmann J, Nicola SM
  • Approach to reward is a fundamental adaptive behavior, disruption of which is a core symptom of addiction and depression. Nucleus accumbens (NAc) dopamine is required for reward-predictive cues to activate vigorous reward seeking, but the underlying neural mechanism is unknown. Reward-predictive cues elicit both dopamine release in the NAc and excitations and inhibitions in NAc neurons. However, …
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