The Mechanism of Action Specialist is part of the Tansey Laboratory in the Department of Cell and Developmental Biology at Vanderbilt University and is a key individual responsible for guiding biological analyses of potential anti-cancer agents. Specifically, this individual will oversee and implement mechanism of action studies for drug-like molecules targeting chromatin regulators in cancer. The individual will report directly to the Laboratory Head and will serve as a key point of contact with collaborators at Vanderbilt, contract laboratories, granting bodies, and industry.
The Mechanism of Action Specialist will design, implement, and perform the necessary cellular, molecular genetic, genomic, and in vivo studies to reveal the mechanism of action of novel inhibitors, guide assessment of on-target activity, and provide information to guide structure-activity relationships. Where necessary, the Mechanism of Action Specialist will also develop and optimize assays to quantitatively assess compound activity in cells, identify and validate patient selection and pharmacodynamic biomarkers, and establish molecular vulnerabilities and potential mechanisms of resistance. The Mechanism of Action Specialist will also train and supervise laboratory personnel working on drug discovery projects, prepare related grants, grant reports, and presentations, and liaise with present and potential collaborators engaged in all aspects of the drug discovery projects.
The Department of Cell and Developmental Biology (CDB) is a vibrant, interdisciplinary, environment for cutting-edge research over a scale that spans from single molecules to whole organisms. CDB is an interactive and highly collaborative department, with a strong cohort of trainees, outstanding core facilities, and exceptionally strong faculty. The Tansey Laboratory performs cutting-edge research on the mechanisms of transcriptional and chromatin dysregulation in cancer, with a specific focus on MYC--an oncoprotein transcription factor responsible for the cancer related deaths of 100,000 Americans every year. The Tansey laboratory seeks to understand the molecular actions of MYC and leverage this information to discover new avenues for therapeutic intervention in malignancies. The Tansey Laboratory has a long-standing collaboration with the Laboratory of Dr. Stephen Fesik (Department of Biochemistry) to discover and refine small molecule inhibitors that can block critical MYC functions in cancer cells, and uses sophisticated molecular, genetic, genomic, and in vivo approaches to provide companion biology for these efforts.
Duties and Responsibilities
Design and implement mammalian cell culture-based assays to track on-target inhibitor function in cells. Outcome should be successful and quantitative assays for prioritizing compounds and compound series and for informing structure activity relationships.
Design and implement assays to describe phenotypic response of cells to inhibitors (growth, apoptosis, cell cycle, etc.). Outcome should be successful and quantitative assessment of cellular response to inform mechanism of action.
Design and implement assays to track molecular actions of inhibitors in cells, using gene-specific and genomic approaches, as well as proteomic strategies. Outcome should be successful and quantitative understanding of mechanism of action, identification of on-target functions, and comprehensive understanding of actions of inhibitors on chromatin-centric processes.
Design and implement assays to functionally interrogate inhibitor function using genome-wide CRISPR-based approaches. Outcome should be successful identification of molecular vulnerabilities, patient selection and pharmacodynamic biomarkers, and potential mechanisms of resistance.
Design and implement assays to interrogate inhibitor function in mouse models of cancer, and to analyze response of tumor tissues to inhibitor treatment. Outcome should be successful biomarker confirmation and confirmation of mechanism of action in vivo.
Recruit and train laboratory personnel for related drug discovery projects. Outcome should be successful recruitment and increase in research output.
Collaboratively prepare and write grant applications and reports related to drug discovery efforts. Outcome should be successful accrual of resources or continuation of existing funding streams.
Collaboratively prepare and deliver presentations and updates to collaborators, funders, and potential partners. Outcome should be successful acquisition of new funding, continuation of existing funding, or establishment of new partnerships.
This position does have supervisory responsibility of laboratory personnel working on drug discovery projects. These personnel could include undergraduate researchers, research technicians, graduate students, and postdoctoral fellows. This position reports administratively and functionally to the Laboratory Head.
A PhD in molecular biology, molecular genetics, genomics, or related topics is necessary.
Experience with mammalian cell culture methods including generation of stable cell lines is strongly preferred.
Experience with standard molecular biology techniques (PCR, subcloning, site-directed mutagenesis, western blotting, genomic DNA isolation, RNA isolation, RT-qPCR, etc.) is strongly preferred.
Experience with CRISPR-based technologies (CRISPRa, CRISPRi, CRISPRko) is preferred.
Experience in contemporary molecular genomic studies (RNA-Seq, ChIP-Seq, etc.) is strongly preferred.
Experience with next-generation sequencing data analysis and visualization is preferred.
Experience with mass spectrometry-based proteomics is preferred.
Experience in working with mice and mouse models of cancer is preferred.
Commitment to Equity, Diversity, and Inclusion
At Vanderbilt University, we are intentional about and assume accountability for fostering advancement and respect for equity, diversity, and inclusion for all students, faculty, and staff. Our commitment to diversity makes us who we are. We have created a community that celebrates differences and lets individuality thrive. As part of this commitment, we actively value diversity in our workplace and learning environments as we seek to take advantage of the rich backgrounds and abilities of everyone. The diverse voices of Vanderbilt represent an invaluable resource for the University in its efforts to fulfill its mission and strive to be an example of excellence in higher education.
Vanderbilt University is an equal opportunity, affirmative action employer. Women, minorities, people with disabilities and protected veterans are encouraged to apply.
Please note, all candidates selected for an offer of employment are subject to pre-employment background checks, which may include but are not limited to, based on the role for which they have been selected: criminal history, education verification, social media review, motor vehicle records, credit history, and professional license verification.
Internal Number: 10000984
About Vanderbilt University
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