Postdoctoral and Research Scientist positions (Müschen Laboratory, Center of Molecular and Cellular Oncology) https://twitter.com/MuschenLab
- Yale University
- Location: New Haven, CT
- Job Number: 7118911
- Posting Date: Dec 22, 2022
- Application Deadline: Open Until Filled
Recent work of the laboratory:
• We discovered regulation of energy-abundance as the central determinant of negative B-cell-selection: Hyperactivation of kinases downstream of an autoreactive B-cell receptor induces ATP-depletion and energy stress (Chen Nature 2015, Shojaee Nature Med 2016, Chan Nature 2017; Pan PNAS 2020).
• Studying changes of energy-metabolism during B-cell transformation, we discovered that glucose carbon-flux was diverted in way that left transformed B-cells uniquely vulnerable to inhibition of PP2A, an enzyme that coordinates glycolytic flux with antioxidant protection (Xiao Cell 2018).
• We discovered that changes in cell-size are orchestrated by BCL6 and MYC. Opposed by MYC, BCL6 decreases cell-size by transcriptionally repressing glucose-uptake in favor of autophagy (Duy Nature 2012; Geng Cancer Cell 2015; Hurtz Genes & Dev 2019).
• Tracking mechanisms of leukemia-initiation in 1,100 patients, we discovered pathway convergence as a novel therapeutic vulnerability in B-ALL. Only mutations that converged on one central pathway promoted leukemia-progression. Genetic reactivation of divergent (suppressed) pathways engaged conflicting biochemical and transcriptional programs and subverted leukemia-development. Pharmacological pathway-reactivation to create a diverse signaling-environment represents a novel strategy to prevent B-ALL relapse and drug-resistance (Chan Nature 2020).
• Studying biophysical mechanisms of B-cell activation, we discovered the short endosomal protein IFITM3 as central scaffold for lipid-raft assembly and surface-expression of rafts-associated receptors. Membrane-recruitment of IFITM3 was essential for the initiation of PI3K-signaling, antibody affinity maturation and oncogenic B-cell transformation (Lee Nature 2021).
Center of Molecular and Cellular Oncology
300 George Street
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