Postdoctoral scientist, Müschen Laboratory

Postdoctoral scientist, Müschen Laboratory

City of Hope

Los Angeles, CA, United States

Postdoctoral scientist, Müschen Laboratory

Department of Systems Biology, City of Hope Comprehensive Cancer Center

Our group is interested in comparative analyses of normal lymphocyte development and malignant transformation towards leukemia. We cover research areas with relevance to Immunology, Hematology and Cancer Biology. Our research involves experiments with primary human leukemia cells, normal lymphocyte development in humanized mice, leukemia and stem cell transplantation models, mouse genetics, gene editing, genetic biosensors of signal transduction, optogenetics, classical molecular and cell biology, a strong emphasis on mechanistic studies in oncogenic signal transduction.

Qualifications: PhD in cell or molecular biology, enthusiasm for science, willingness to think beyond established concepts and to try and learn new experimental and analysis tools. The lab takes a team science approach, so being a nice person and a good team player is important as well.

Your application should include in one single PDF:
CV, brief motivation statement, coordinates of three scientific mentors (references)

Methods/Techniques: Flow cytometry, mass spectrometry/quantitative phosphoprofiling, genetic biosensors of signal transduction, optogenetics, mouse genetics, bone marrow transplantation assays, retroviral gene delivery, whole exome sequencing and RNA-seq-analysis of clonal evolution of leukemia, pre-clinical drug testing in xenotransplantation models.

Recent work of the laboratory: Studying more than 800 patients, our group discovered a new subtype of leukemia (~15%) that can be treated with small molecule antagonists of pre-B cell receptor signaling, a new therapeutic concept that is now being tested in a clinical trial (Cancer Cell 2015). In addition, a recent study from our lab provided a mechanistic explanation for clonal evolution of normal B-cells towards leukemia (Nature Immunology 2016). Our group discovered that B-cell tumors are subject to a unique autoimmunity checkpoint for removal of self-reactive B-cells. Targeted hyperactivation of SYK (Nature 2015), PI3K (Nature Medicine 2016) and ERK (Cancer Cell 2015) in B-cell malignancies represents the functional equivalent of an autoimmunity checkpoint (AIC) to prevent B-cell autoimmunity. AIC-activation is achievable by pharmacological hyperactivation of SYK, PI3K and ERK, thereby leveraging mechanisms of negative selection in the immune system for targeted cancer therapy (Nature Rev Cancer 2018). Most recently, the Müschen laboratory discovered that B-lymphoid transcription factors serve a novel gatekeeper-function by limiting energy-supply to levels that are insufficient to fuel oncogenic transformation (Nature 2017). The full range of metabolic gatekeeper functions of B-cell transcription factors, including their ability to suppress the pentose phosphate pathway (PPP) in B-cell malignancies was revealed in a follow-up study (Cell 2018).

https://www.cityofhope.org/research/systems-biology
http://www.hhmi.org/scientists/markus-muschen

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Postdoctoral scientist, Müschen Laboratory