Associate Principal Scientist; Associate Director

Job Title:

Associate Principal Scientist

Location:

Waltham, MA

The Rare Cancer Unit is a dedicated group within AstraZeneca Oncology R&D focused on discovering and advancing transformative therapies for patients with rare and underserved cancers—including neuro-oncology, and other rare malignancies of high unmet needs, where standard-of-care options are limited or nonexistent. The Unit works across modalities including small molecules, biologics, bioconjugates, targeted protein degraders (PROTACs), gene therapy (AAV/lentivirus), RNA/mRNA therapeutics, and cancer vaccines, and partners closely with translational medicine, clinical development, and external academic collaborators to accelerate first-in-class programs into the clinic.

The Associate Principal Scientist /Associate Director will provide scientific leadership and hands-on experimental expertise to rare cancer discovery programs, with a primary focus on neuro-oncology indications such as glioblastoma and pediatric brain tumors. The successful candidate will design and execute complex biology experiments across advanced in vitro and orthotopic in vivo models, interpret data to guide program direction, and serve as a key scientific voice across cross-functional teams spanning oncology, immuno-oncology, viral vector engineering, and targeted protein degradation.

• Lead and contribute to discovery programs aimed at identifying novel therapeutic strategies for rare CNS cancers, including glioblastoma and pediatric brain tumors, encompassing target validation, mechanism-of-action (MOA) studies, and translational research.
• Design and execute complex in vitro and in vivo experiments, including 2D/3D glioma models, patient-derived and cell line–derived xenografts, syngeneic mouse models, orthotopic intracranial implantation, and in vivo bioluminescence imaging.
• Engineer tumor models via lentiviral transduction, AAV delivery, CRISPR/Cas9 editing, and si/shRNA knockdown to over express or ablate targets of interest.
• Advance targeted protein degradation strategies (PROTACs) for oncoprotein degradation in brain and other rare tumors, building on established programs in BRD4 and related targets.
• Evaluate novel immunotherapy approaches, targeting TAA and beyond and immune cell engagers, in relevant preclinical models.
• Assess the impact of standard of the care (chemo/radiation, TTF, and combination therapies) on target expression, tumor behavior, and tumor microenvironment dynamics specific to neurooncology.
• Analyze and interpret experimental data to evaluate therapeutic hypotheses, assess efficacy, potency, and safety signals, and inform go/no-go program decisions.
• Serve as scientific liaison across functions, including Neuroscience, Immuno-Oncology, Translational Medicine, and Clinical Development, to advance integrated therapeutic strategies for rare CNS cancers.
• Present scientific findings to internal leadership, governance committees, and external partners; contribute to publications, patents, and regulatory documents.
• Provide scientific mentorship to junior scientists, associates, and postdoctoral fellows, and ensure technical rigor across the team.
• Contribute to portfolio strategy by shaping experimental roadmaps, identifying novel targets, and evaluating external opportunities including academic collaborations and in-licensing.

• PhD in Cell Biology, Cancer Biology, Molecular Biology, or a closely related discipline.
• 5+ years of postdoctoral and/or industry experience in oncology drug discovery or translational research, with demonstrated productivity in neuro-oncology.
• Demonstrated expertise in glioblastoma and pediatric brain tumor (DIPG) biology, advanced cellular models, and orthotopic intracranial in vivo models.
• Hands‑on experience with AAV and lentivirus production, CRISPR/Cas9 engineering, and viral vector–based therapeutics.
• Experience with targeted protein degradation (PROTACs) and small‑molecule mechanism‑of‑action characterization.
• Strong publication record in peer‑reviewed journals in oncology, neuro‑oncology, and molecular biology.
• Proven ability to work in cross‑functional, matrixed…