Jobs Postings
Postdoctoral Scientist, Müschen Laboratory
Center of Molecular and Cellular Oncology, Yale University
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. We strive to promote a culture of diversity and inclusivity for all its members, focusing on career development and innovative approaches to science.
Qualifications: Ph.D. in cell or molecular biology, enthusiasm for science, willingness to think beyond established concepts and to try and learn new experimental and analytical tools. The lab takes a team science approach, being collaborative is important as well.
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: To prevent the production of harmful autoantibodies and autoimmune disease, autoreactive B-cells and pre-malignant clones are eliminated by a process termed negative selection. Despite strict and rigorous negative selection, B-cells frequently give rise to autoimmune diseases and B-cell malignancies such as leukemia and lymphoma. Since humans can live without B-cells for extended periods of time, the Müschen laboratory systematically investigated lineage-specific vulnerabilities that are common in B-cell leukemia/lymphoma but not any other cell type. Contrary to the established dogma, these mechanisms are not only active in preventing autoimmune disease but also represent a novel class of therapeutic oncogenic targets in malignant B-cell tumors. Over the past five years, the Müschen Laboratory established innovative conceptual frameworks for the understanding of B-cell signaling mechanisms and negative selection, some of which are summarized below:
• 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 a 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 that the short endosomal protein IFITM3 acts as a 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 2020).
Your application should include in one single PDF:
CV, a brief statement of motivation, and contacts of three scientific mentors (references) sent to Dr. Markus Müschen via email (markus.muschen@yale.edu).
Postgraduate Associate Opening at the Müschen Laboratory
Center of Molecular and Cellular Oncology, Yale School of Medicine
Job Description: We are seeking a highly motivated postgraduate research associate interested in joining the Müschen Lab to gain experience in the fields of cancer genomics, systems biology, and bioinformatics. You will have the opportunity to work with a team of scientists dedicated to studies on B-cell development and targeted cancer therapy. Our research involves experiments with leukemia cells, mouse models, and we largely employ molecular and cellular biology tools to understand the mechanisms driving malignant transformation through signaling pathways. Under the guidance of Dr. Markus Müschen and senior lab members, you will also have the opportunity to contribute to the ongoing research projects and take part in high-impact publications. This is a full-time position available for 1-year with the possibility of renewal.
Over the past 12 years, our laboratory has developed a multidisciplinary research program focused on oncogenic signaling and clonal evolution in B-cells. Antibody-producing B-cells are under intense selective pressure to remove autoreactive and pre-malignant clones, yet autoimmune disorders and B-cell malignancies such as leukemia are very common and often incurable diseases. By understanding the mechanisms of B-cell selection, we are able to explore new therapeutic targets in B-cell tumors. Our scientific discoveries are driven by the desire to create a stimulating academic environment where we focus on rigorous, collaborative, and innovative science.
You will work closely with our senior scientists to help advance their innovative research projects focused on B-cell development, mechanisms of negative selection and approaches to therapeutic targets in B-cell malignancies. We rely heavily on molecular and cellular approaches, so you must be enthusiastic and willing to learn about new techniques and technologies in the field of genomics, proteomics, transcriptomics to tackle your work. This training will promote your understanding of cancer biology and you will be able to contribute to exciting research projects in a multidisciplinary setting. Prior experience handling experimental mice (injection, genotyping, colony maintenance) is a plus given that we use genetic mouse models to address normal and malignant hematopoiesis. You will be expected to actively participate in our weekly lab meetings, provide work-in-progress updates, and take part in our scientific club discussions. You will also work closely with our lab manager and assist him with the general upkeep of the lab and organizing our inventory.
In the laboratory, we promote a culture of inclusivity, mentoring our trainees’ scientific growth, and striving to make science accessible to everyone. Through daily interactions with senior lab members and weekly sessions with Dr. Müschen, you will have the support necessary to develop into a successful independent scientist if that is your goal. You will be given advice on career development and will have the opportunity to conduct your own project(s).
Requirements:
Bachelor’s or Master’s degree in biological sciences or related field with practical experience in basic molecular and cell biology techniques (e.g., cell culture, protein chemistry, western blotting, quantitative PCR, cloning, etc). Basic knowledge of cancer genomics, immunology or hematology is a plus.
Your application should include in one single PDF:
CV, a brief statement of motivation, and contacts of three scientific mentors (references) sent to Dr. Markus Müschen via email (markus.muschen@yale.edu).
Bioinformatics Research Associate, Müschen Laboratory
Center of Molecular and Cellular Oncology, Yale School of Medicine
We are currently seeking a highly motivated postgraduate associate with experience in bioinformatics to join the Müschen Lab in the Center of Molecular and Cellular Oncology at the Yale Cancer Center. Our multidisciplinary team bridges clinical, genetic and computational approaches to understanding mechanisms of oncogenic signaling and B-cell selection, allowing us to explore novel therapeutic strategies in B-cell malignancies including B-ALL, CLL and MCL. Our scientific discoveries are driven by the desire to create a stimulating academic environment where we focus on rigorous, collaborative and innovative science.
You will work closely with our bioinformatics teams to hone your computational skills and collaborate with bench scientists to explore biological questions. Career development and project guidance will be provided by frequent discussions with Dr. Müschen. The assignments will focus on high-throughput data analysis and interpretation - from raw data sequence processing through to biological insights and visualization and for presentation and publication. Techniques include proteomics, phosphoproteomics, ChIP-seq, transcriptomics, single-cell BCR- and RNA-sequencing and genomics. This includes both analyses of public datasets for identification of B-cell specific vulnerabilities and internally generated datasets to answer hypothesis-driven questions. This is a great opportunity to develop command-line scripting, high-performance computing environments, R- and python programming, and data visualization. In addition to technical training, you will gain an in-depth understanding of molecular oncology, specifically in B-cell malignancies. Prior experience or familiarity with analysis pipelines, algorithms, or experimental protocols for any of the above techniques would be considered a plus.
In the laboratory, we promote a culture of inclusivity, mentoring our trainees’ scientific growth, and striving to make science accessible to everyone. It’s our aim that through daily guidance from our lead bioinformatician and weekly sessions with Dr. Müschen you will have the support necessary to develop into a successful independent scientist. You will also have the opportunity to attend conferences and courses on programming, bioinformatics, machine learning and oncology. Participation in Yale’s mentorship program is also strongly encouraged.
A Bachelor’s or Master’s degree in any biological, computational or other quantitative science is required for this position. A track record of experience in bioinformatics - either coursework or practical experience is preferred. To excel in this role you must have a passion for exploring challenging research questions in an interdisciplinary team setting, be organized, motivated and have excellent communication and problem-solving skills. Experience in the fields of cancer genomics or hematology is preferred but not required.
Your application should include in one single PDF:
CV, a brief statement of motivation, and contacts of three scientific mentors (references), sent to Dr. Markus Müschen via email (markus.muschen@yale.edu).
Yale Cancer Center invites applications for a physician-scientist faculty position at the Assistant Professor level. Applicants should have an exceptional track record of scientific innovation. A track record of extramural funding is preferred. We seek an outstanding investigator to join our interdisciplinary Center for Molecular and Cellular Oncology that is focused on understanding key mechanisms of cancer biology and translating this understanding into novel therapeutic and diagnostic approaches. New faculty will be supported with competitive start-up packages, laboratory space, access to laboratory animal facilities, and a wide range of state-of-the-art core facilities. The successful candidate is expected to initiate and maintain a vigorous, independent, extramurally funded research program, and participate in the training of medical and graduate students and postdoctoral and clinical fellows. Yale Cancer Center is dedicated to the development and advancement of biomedical research to eliminate cancer and provides a unique environment for conducting innovative basic, translational, population, and clinical research. The successful candidate will be a full member of the Center for Molecular & Cellular Oncology and, depending on their clinical activity, will join one of the clinical sections of Yale Cancer Center. Applicants further along in their career may be considered for a faculty position commensurate with experience. Yale values diversity in its faculty, students, and staff and strongly encourages applications from women, members of minority groups, persons with disabilities, and protected veterans. Review of applications will begin January 15, 2022 and continue until the position is filled.
All application materials, including your curriculum vitae and a statement of current research activities and future goals (2 pages), and a one-page statement of contributions to diversity and inclusion should be submitted electronically to: https://apply.interfolio.com/98674
Any questions regarding the application process should be directed to: Yale Cancer Center, c/o Anna Raso, 333 Cedar St., PO Box 208028, New Haven, CT 06520-8028 or via email to anna.raso@yale.edu
Postdoctoral Fellow (Ishizuka Lab)
We are seeking creative and driven scientists to lead projects within the Ishizuka Lab. The candidate should have a strong background in biology, with a strong interest in immunology and / or cancer biology research. Experience with in vivo immunotherapy models, functional genomics and the use of CRISPR, protein engineering, systems immunology, and tumor microenvironment profiling by scRNAseq / flow cytometry are preferred. The ideal candidate will additionally possess excellent experimental planning and execution skills, good communications skills, an open mind and a desire to collaborate with others. The chosen individual will lead independent research projects, report progress and track deliverables, work to develop new approaches and ways of thinking about the field of tumor immunology, contributing to the lab through teamwork and discussions, help train, supervise and mentor junior staff as needed.
Qualifications: Minimum qualifications include a PhD in a relevant field (biology, immunology, cancer biology or similar), demonstrated scientific contributions to the field, proven ability to solve challenging technical problems, clarity of thought in communications (written and oral).
To apply, please email your CV and a cover letter with contact information for three references to jeffishizukalab@gmail.com
Postgraduate Research Associate (Ishizuka Lab)
The Ishizuka Lab is recruiting a wet lab research associate to join a team dedicated to identifying novel targets for cancer immunotherapy and new approaches to profiling patient samples. The candidate will function both independently to drive projects and as part of a team with other lab members. The successful candidate will initially be asked to support an ongoing project which includes using functional genomic screening and microscopy to identify new therapeutic targets for cancer. He/she will be expected to design and conduct experiments in a reproducible manner, to interpret results, to conduct independent analysis and to participate in purchasing and other tasks critical to the day-to-day operations of the lab.
Qualifications: This position requires a Bachelor’s degree in biology, engineering or other science-related field. Experience with cell culture, molecular biology and in vivo tumor modeling experience are preferred. Must have demonstrated ability to think creatively and to solve problems with a strong attention to detail, strong interpersonal, communication and organizational skills, abundant motivation with the ability to work both independently and as part of a team.
Training Provided: The candidate will work closely with other lab members and the principal investigator to develop expertise in: Experimental approaches in cell and molecular biology, potentially including cell culture, microscopy, immunofluorescence, molecular cloning and western blotting; experimental approaches in immunology potentially including flow cytometry, cytokine bead arrays and intracellular cytokine staining; experimental approaches in genomics, functional genomics and transcriptomics potentially including CRISPR-Cas9 screening, next generation sequencing, bulk and single cell RNAseq; tumor immunology and communication / presentation via lab meetings, journal clubs and informal discussion.
Mentoring Provided: The principal investigator meets with every lab member weekly to review data, discuss goals and provide feedback and advice. The candidate will additionally work closely with a post-doctoral fellow in the Lab with expertise in the project selected.
To apply, please email your CV and a cover letter with three references to: jeffishizukalab@gmail.com
Laboratory Manager (Ishizuka Lab)
The Ishizuka lab is recruiting a lab manager to join a team dedicated to identifying novel targets for cancer immunotherapy and new approaches to profiling patient samples. The candidate will play a critical role in multiple aspects of the lab, including but not limited to maintenance of lab protocols and SOPs, purchasing of equipment and reagents, lab organization and serving as a central contact for lab members and people outside the lab. Additionally, the candidate will participate in driving and executing research projects within the lab in collaboration with other team members and the Principal Investigator. With respect to participation in research projects, the successful candidate will be expected to design and conduct experiments in a reproducible manner, to interpret results and to conduct independent analysis.
Qualifications: Bachelor’s degree in biology, engineering or other science-related field. In vivo tumor modeling, statistical analysis, cell culture and molecular biology experience are preferred but not required. Formal or informal experience in a lab management capacity. Must have demonstrated ability to think creatively and to solve problems with a strong attention to detail, strong interpersonal, communication and organizational skills, abundant motivation with the ability to work both independently and as part of a team.
To apply, please email your CV and a cover letter with three references to: jeffishizukalab@gmail.com
Postdoctoral Fellow (Wilson Lab)
Applicants must have a recent PhD degree in a relevant field and at least one first author publication in a peer-reviewed journal. Applicants should have experience in molecular biology, genetics / genomics, tumor cell biology, or other related fields. Excellent written and oral communication skills are expected.
Candidates should send a Curriculum Vitae, a statement of research interests and career goals and the names / contact information for three references to: frederick.wilson@yale.edu.
We are recruiting both graduate and undergraduate students. If you are interested in joining the lab, please email your CV and a brief introduction to: jeffishizukalab@gmail.com