Postdoctoral Fellow - Lymphocyte Development And Malignant Transformation Towards Leukemia - Müschen Laboratory

About City of Hope City of Hope, an innovative biomedical research, treatment and educational institution with over 6,000 employees, is dedicated to the prevention and cure of cancer and other life-threatening diseases and guided by a compassionate, patient-centered philosophy. Founded in 1913 and headquartered in Duarte, California, City of Hope is a remarkable non-profit institution, where compassion and advanced care go hand-in-hand with excellence in clinical and scientific research. City of Hope is a National Cancer Institute designated Comprehensive Cancer Center and a founding member of the National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers that develops and institutes standards of care for cancer treatment. Position Summary The Müschen Laboratory in the Department of Systems Biology at the Beckman Research Institute of City of Hope is looking for a talented Postdoctoral Fellow. This lab is interested in comparative analyses of normal lymphocyte development and malignant transformation towards leukemia. Research areas with relevance to Immunology, Hematology and Cancer Biology are covered. Research involves experiments with primary human leukemia cells, normal lymphocyte development in humanized mice, leukemia and stem cell transplantation models, mouse genetics, gene editing, optogenetics, classical molecular and cell biology, a strong emphasis on mechanistic studies in oncogenic signal transduction. Methods/Techniques: Flow cytometry, mass spectrometry/quantitative phospho-profiling, CyTOF, 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. Qualifications Basic education, experience and skills required for consideration: 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. Additional Information: Please submit, in a single PDF, your curriculum vitae and a brief motivation statement. 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: ). City of Hope is committed to creating a diverse environment and is proud to be an equal opportunity employer. All qualified applicants will receive consideration for employment without regard to race, religion, color, national origin, sex, sexual orientation, gender identity, age, status as a protected veteran, or status as a qualified individual with disability.

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