Drug Mechanism of Action Scientist

Job ID: req3945
Employee Type: exempt full-time
Division: Applied & Development Research Program
Facility: Frederick: Ft Detrick
Location: PO Box B, Frederick, MD 21702 USA

The Frederick National Laboratory is a Federally Funded Research and Development Center (FFRDC) sponsored by the National Cancer Institute (NCI) and operated by Leidos Biomedical Research, Inc. The lab addresses some of the most urgent and intractable problems in the biomedical sciences in cancer and AIDS, drug development and first-in-human clinical trials, applications of nanotechnology in medicine, and rapid response to emerging threats of infectious diseases.

Accountability, Compassion, Collaboration, Dedication, Integrity and Versatility; it's the FNL way.

PROGRAM DESCRIPTION

The Frederick National Laboratory for Cancer Research (FNLCR) is a Federally Funded Research and Development Center sponsored by the National Cancer Institute (NCI) and operated by Leidos Biomedical Research, Inc. With more than 2,000 employees, the FNLCR is responsible for pursuing a mission of translational and applied biomedical research that is unique from academia, the pharmaceutical industry, or other federal contractors. The selected candidate will join a newly created FNLCR laboratory at the NCI-Frederick campus that is within the NCI Molecular Pharmacology Branch (MPB), which employs state-of-the-art approaches to discover novel targets, evaluate investigational therapeutics, and develop novel drug combinations to improve treatment of recalcitrant, rare, and neglected cancers.

The successful candidate will carry out experimental studies to elucidate the underlying mechanism of action (MOA) of novel oncology drugs and their combinations that have demonstrated strong, unexpected and inexplicable efficacy (e.g., combination activity for Drug A plus Drug B despite the absence of Drug A’s target) in preclinical models and/or cancer patients. The scope of these projects will encompass employing computational skills to analyze existing NCI databases and other sources of preclinical and clinical study results to formulate MOA hypotheses that are testable with well-designed experiments on molecular targets, biochemical pathways, cellular responses, tumor heterogeneity, drug response and resistance, and immunological response (both innate and adaptive). It is likely that the drug combinations selected for study will require the use of different technologies and tumor model systems available not only at NCI-Frederick but also in the broader NIH and external research communities to fill knowledge gaps in existing datasets using, for example, biochemical studies, single- and co-culture cell-based 2D and 3D in vitro tumor models (e.g. monolayers, spheroids and organoids), and genetically engineered or otherwise manipulated cell lines or mouse models that are immunocompetent or harbor particular defects of the immune system. It is also likely that wide-ranging experimental approaches will be required to test the MOA hypotheses, including enzymatic studies, labeling of cell types (e.g., fluorescent markers or genetic barcodes), proteomics and single-cell RNA sequencing, spatial transcriptomics, and high-resolution tissue imaging. Success in this role will require extensive knowledge of pharmacology and cancer biology as well as experience with wide-ranging experimental methods and model systems suitable for pharmacodynamic studies.

KEY ROLES/RESPONSIBILITIES

• Use scientific knowledge and experience as well as technical expertise to contribute to the development of hypotheses for the mechanism of action (MOA) of drug combinations of programmatic interest to the NCI Division of Cancer Treatment & Diagnosis by systematically analyzing and interpreting a range of preexisting preclinical and clinical data on target inhibition, drug synergy, therapeutic response in laboratory models and/or in cancer patients, predictive and drug-response biomarkers, multi-omics, pharmacokinetics, toxicology, and immunology.
• Contribute to the design, presentation, and coordination of necessary experimental work to fill knowledge gaps and then to directly test the MOA hypotheses, some of which research will be collaborative work within a team as well as with other groups, including the FNLCR Molecular Characterization Laboratory (MoCha), Proteomics Characterization Laboratory, Clinical Pharmacodynamic Biomarkers Program, and the NCI Biological Testing Branch.
• Conduct experiments to test and refine the MOA hypotheses of the selected drug combinations by leveraging appropriate experimental methods, technologies, and tumor models.
• Contribute experimental results and other scientific findings along with sound interpretation of results to developing manuscripts about newly identified MOAs of drug combinations.

BASIC QUALIFICATIONS

To be considered for this position, you must minimally meet the knowledge, skills, and abilities listed below:

• Possession of a doctoral degree in a biomedical field (e.g., D.V.M., D.Sc., M.D., or Ph.D.) from an accredited college or university according to the Council for Higher Education Accreditation (CHEA. Foreign degrees must be evaluated for U.S. equivalency
• Demonstrated expertise in applying experimental methods that are relevant for investigating drug MOA and pharmacology, for example methodology from the fields of cell biology, immunology, genetics, genomics, molecular biology, biochemistry, chemistry, enzymology, pharmacology, drug discovery and/or similar disciplines.
• Training and experience in bioinformatics & data sciences relevant to drug MOA/pharmacology and the ability to perform computational analyses of large multi-omics datasets.
• Expertise in interrogating, interpreting, and summarizing large volumes of data by appropriate statistical analytical procedures and reporting practices to provide scientific insight.
• Must be an excellent team player, able to thrive in a collaborative setting, and forward-thinking with exceptional experimental, record-keeping, and problem-solving skills.
• Must have high integrity and standards for research rigor and reproducibility.
• Excellent written and verbal communication, troubleshooting, and organizational skills, including excellent skills at converting laboratory research findings into clear and meaningful presentations and documents.
• Ability to obtain and maintain a security clearance.

PREFERRED QUALIFICATIONS

Candidates with these desired skills will be given preferential consideration:

• Productive experience conducting innovative experimental investigations into drug mechanisms of action that demonstrate the creativity, independent thinking, and talent for converting ideas into laboratory experiments.
• Productive experience with experimental immunology and/or immunotherapeutics.
• Productive experience in computational analyses of large data sets, appropriate statistical analytical procedures, and accurate interpretations to provide scientific insights into drug pharmacology and MOA.
• Productive expertise in applying high-resolution laboratory imaging and microscopy methodologies to interrogate patient-derived tumor models.
• Prior experience in an applied R&D environment, such as a research institute, the pharmaceutical sector, and/or the biotechnology sector.
• Scientific contributions that are relevant to drug MOA such as independently producing research work, authoring and/or co-authoring publications in peer-reviewed scientific journals, and by presenting papers before professional societies.

Commitment to Diversity
All qualified applicants will receive consideration for employment without regard to sex, race, ethnicity, age, national origin, citizenship, religion, physical or mental disability, medical condition, genetic information, pregnancy, family structure, marital status, ancestry, domestic partner status, sexual orientation, gender identity or expression, veteran or military status, or any other basis prohibited by law. Leidos will also consider for employment qualified applicants with criminal histories consistent with relevant laws.
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