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.

The laboratory of Dr. Mitchell Weiss at 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.

Collaborate with medicinal chemists, cell and molecular biologists, biochemists, and structural biologists to support compound development and mechanistic characterization.

Assist in preparing scientific manuscripts, posters, presentations, standard operating procedures (SOPs), and research reports.

Maintain current knowledge of relevant scientific advances, methodologies, and technologies.

Provide guidance and technical training to less-experienced laboratory personnel and collaborators as appropriate.

Support laboratory operations, including equipment maintenance, calibration, inventory management, and ordering of supplies.

Perform other duties as assigned to support departmental and institutional research objectives.

Maintain regular and predictable attendance.

Qualifications and Experience:

Preferred Qualifications

• PhD in Molecular Biology, Cell Biology, Biochemistry, Biomedical Sciences, Pharmacology, or a related field is preferred.
• Strong experimental background in mammalian cell culture, molecular biology, biochemistry, or cellular assays.
• Experience with techniques such as immunoblotting, flow cytometry, gene expression analysis, and protein characterization.
• Experience with high-throughput experimentation.
• Demonstrated ability to independently plan, execute, troubleshoot, and analyze experiments.
• Strong analytical, organizational, communication, and scientific problem-solving skills.
• Ability to work effectively in a collaborative, multidisciplinary research environment.
• Additional Experience Considered an Advantage
• Experience in erythroid biology, hemoglobin regulation, hematopoiesis, or sickle cell disease research.
• Familiarity with targeted protein degradation technologies, including PROTACs, molecular glues, E3 ubiquitin ligases, and the ubiquitin-proteasome system.
• Experience with primary human erythroid or hematopoietic cell cultures.
• Experience with preclinical mouse models or translational drug discovery research.
• Prior experience in erythroid biology or targeted protein degradation is a plus but is not essential .
• Candidates with strong experimental skills, scientific curiosity, good communication skills, team spirit and a willingness to learn new techniques are strongly encouraged to apply.
• Research Environment and Opportunities: The Associate Scientist will join a highly collaborative and intellectually stimulating research environment, working alongside experienced Senior Scientists, postdoctoral fellows, and interdisciplinary collaborators.

This position offers opportunities to contribute to innovative therapeutic discovery, gain expertise in emerging protein degradation technologies, and participate in research spanning mechanistic studies, compound optimization, and preclinical development.

By integrating fundamental discoveries in erythroid biology with advances in chemical biology and targeted protein degradation, our team aims to develop next-generation therapeutic strategies capable of increasing fetal hemoglobin expression and improving outcomes for patients with sickle cell disease.

We welcome applications from enthusiastic, creative, and collaborative scientists who are passionate about advancing innovative research with meaningful clinical impact.

Minimum Education and/or Training:

Bachelor’s degree in a relevant scientific area

Minimum Experience:

• 7 + years of research experience is required
• 5 + years of research experience is required with a Master’s degree
• 2 + years of research experience is required with a PHD
• Experience leading and supporting research experiments preferred
• Some experience leading lab and scientific project coordination, maintenance, and other research support activities preferred
• Experience in guiding and training other laboratory personnel preferred
• Proven performance in earlier role/comparable role