Associate Scientist - Targeted Protein Degradation and Fetal Hemoglobin Induction

The Associate Scientist performs a variety of moderately complex research tasks determined by the field and scope of the particular research project/study. Also, performs tasks related to the research project independently, but within broad guidelines and subject to periodic review by supervisor or other research staff.

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The laboratory of Dr. Mitchell Weissat St. Jude Children's Research Hospital is seeking a highly motivated Associate Scientist to join an innovative, multidisciplinary research program focused on developing novel therapeutic strategies for sickle cell disease through targeted protein degradation (TPD).

This cutting-edge project builds upon our ongoing work developing cereblon (CRBN)-based molecular glues to induce fetal hemoglobin (HbF) and seeks to expand this approach by identifying and leveraging additional erythroid-specific E3 ubiquitin ligases. Our goal is to develop a diverse portfolio of proteolysis-targeting chimeras (PROTACs) and molecular glue degraders that selectively eliminate negative regulators of HbF expression.

The successful candidate will contribute to the discovery, characterization, and preclinical evaluation of these targeted degraders using immortalized erythroid cell lines, primary human erythroblasts, and sickle cell disease mouse models, with the long-term objective of advancing promising therapeutic candidates toward clinical development.

This position provides a unique opportunity to work at the intersection of erythroid biology, chemical biology, protein degradation, and translational therapeutics. The Associate Scientist will work closely with Senior Scientists, postdoctoral fellows, and cross-functional teams of medicinal chemists, molecular and cellular biologists, biochemists, and structural biologists in a highly collaborative, team-based research environment.

Key Research Responsibilities:

• Independently design, perform, optimize, and troubleshoot experiments to evaluate targeted protein degradation strategies for HbF induction.
• Characterize the activity, selectivity, and mechanisms of action of PROTACs and molecular glue degraders targeting negative regulators of HbF expression.
• Evaluate candidate compounds in immortalized erythroid cell lines and primary human erythroblast cultures using molecular, cellular, and biochemical assays.
• Investigate target protein degradation, HbF induction, erythroid differentiation, and relevant cellular responses.
• Contribute to preclinical evaluation of promising compounds in sickle cell disease mouse models.
• Develop and optimize new or modified laboratory techniques and experimental protocols.
• Independently collect, process, organize, analyze, and interpret experimental data, and communicate findings to the research team.