Associate Principal/Senior Scientist, Pharmacology and Toxicology

SUMMARY OF THE ROLE 

You will lead in vivo pharmacology and immune monitoring to enable data-driven progression of programs from discovery toward translation, with priority focus on (1) cell therapy (CAR-T), followed by (2) immuno-oncology and (3) immunology. You will own key humanized mouse platforms and associated ex vivo and in vivo CAR-T characterization workflows, delivering rigorous, decision-enabling datasets that inform candidate selection, dose/regimen strategy, mechanism-of-action understanding, and translational biomarker hypotheses. 

ROLES & RESPONSIBILITIES 

Humanized mouse CAR-T in vivo strategy (core priority): Design and deliver in vivo studies in humanized mouse systems to evaluate CAR-T anti-tumor activity, expansion/engraftment, persistence, trafficking, and pharmacodynamics. Translate program hypotheses into clear endpoints, sampling schedules, and pre-defined decision criteria to support candidate ranking, construct optimization, and combination rationale where relevant. 

Humanized mouse platform ownership and fit-for-purpose selection: Plan and run studies using appropriate humanized mouse approaches (e.g., PBMC-engrafted and/or CD34+ HSC-engrafted models, as fit-for-purpose), including immune reconstitution assessment, feasibility/risk assessment, study timelines, and interpretation of human immune responses in vivo. Proactively communicate model limitations, variability drivers, and implications for decision-making. 

In vitro CAR-T functional characterization (paired with in vivo): Own key ex vivo workflows that connect in vivo findings to mechanism and quality of response, including immune cell phenotyping from blood and tissues, target engagement-relevant readouts, and functional assessments as appropriate (e.g., cytokine release, cytotoxic potential, activation/exhaustion state, and persistence-related signatures). Ensure ex vivo plans are integrated into in vivo sampling strategy to maximize interpretability. 

Oncology modeling and tumor microenvironment readouts (supporting priority): Lead small animal oncology study designs that enable immune-relevant interpretation, including tumor growth inhibition plus immune context readouts (e.g., tumor infiltrating immune cell phenotype, activation state, and changes consistent with mechanism). Drive alignment between model selection, tumor biology, antigen expression considerations, and the intended CAR-T biology. 

Study leadership and vendor/CRO governance: Own end-to-end study delivery through internal vivarium teams and external partners as needed, including protocol writing/review, randomization/blinding where feasible, operational readiness, sample logistics planning, real-time troubleshooting, and report/data package readiness. Set clear scientific expectations and quality checkpoints, ensuring traceability from in-life conduct through bioanalysis and interpretation. 

Hands-on contribution (limited but critical): Maintain practical capability for critical in-life and terminal activities as needed (e.g., dosing support, tumor measurement, blood/tissue collection coordination) and for immune monitoring sample processing. Perform and/or directly oversee flow cytometry-based immunophenotyping (panel review/design, staining strategy, gating review, and interpretation) from blood and tissues to ensure data quality, comparability, and rapid troubleshooting. 

Data, analytics, and documentation: Apply rigorous experimental design principles and pre-specified analysis plans, delivering clear visualizations and concise narratives that support project and governance decisions. Document work to high standards in ELN and associated systems, ensuring data integrity, traceability, and reproducibility. 

Cross-functional collaboration and communication: Drive alignment with Cell Therapy discovery/in vitro teams, Translational Science, Bioanalytics, Pathology, CMC, and Clinical colleagues. Present results, risks, and recommendations in cross-functional forums, and contribute to best-practice standardization and mentoring within the in vivo community. 

REQUIREMENTS 

Education: PhD (or equivalent) in Immunology, Medicine, Pharmacology, Translational Science, Oncology Biology, or related field; or MD with substantial translational/in vivo research experience. 

Small animal in vivo expertise: Demonstrated experience designing and delivering mouse studies in oncology and/or immunology with strong study rigor, including model selection rationale, endpoint definition, and interpretation of efficacy and mechanistic datasets. 

Humanized mouse experience (must-have): Practical experience planning, executing, and interpreting studies in humanized mouse systems for immunotherapy questions, including immune reconstitution assessment and immune monitoring strategy aligned to study objectives. 

CAR-T biology and evaluation literacy: Strong understanding of CAR-T pharmacology questions and how to interrogate them in vivo and ex vivo (e.g., expansion/persistence/trafficking concepts, immune activation and phenotype shifts, and linking endpoints to translational hypotheses). 

Flow cytometry competence: Ability to design/review panels and gating strategies and interpret complex immunophenotyping datasets from blood and tissues; hands-on experience is strongly preferred. 

Study leadership and vendor management: Proven ability to run multiple concurrent studies with high quality and on-time delivery, including protocol rigor, operational planning, and effective collaboration with vivarium teams and external partners. 

Data & tools: Proficiency with ELN and analysis/visualization tools (e.g., GraphPad; FlowJo where relevant), comfort working with multi-modal datasets, and understanding of basic statistics and acceptance criteria for in vivo studies. 

Compliance: Strong animal ethics and welfare mindset (IACUC/ethics committee expectations, 3Rs), biosafety practices, research GxP awareness where relevant, and high standards for data integrity. 

Strong English communication: Demonstrated ability to communicate scientific and operational information clearly in written and spoken English, including presenting study plans and results, facilitating technical discussions, aligning stakeholders on next steps, and summarizing risks/assumptions and trade-offs in concise updates for cross-functional and senior audiences. 

PREFERRED EXPERIENCE 

Experience establishing or scaling humanized mouse CAR-T pipelines with integrated immune monitoring and ex vivo functional characterization. Experience with immune profiling integration across tissues (flow cytometry plus histology/IHC coordination), assay method transfer/comparability across internal and CRO labs, and contributing to translational biomarker strategy is beneficial. Experience supporting immuno-oncology combination strategies (e.g., CAR-T plus modulators) and interpreting tumor microenvironment changes is a plus. 

AstraZeneca embraces diversity and equality of opportunity. We are committed to building an inclusive and diverse team representing all backgrounds, with as wide a range of perspectives as possible, and harnessing industry-leading skills. We believe that the more inclusive we are, the better our work will be. We welcome and consider applications to join our team from all qualified candidates, regardless of their characteristics. We comply with all applicable laws and regulations on non-discrimination in employment (and recruitment), as well as work authorisation and employment eligibility verification requirements.