Postdoctoral Research Fellow - Sethi Lab

The Sethi Laboratory at Dana-Farber Cancer Institute and Harvard Medical School is seeking an outstanding experimental postdoctoral fellow to study the molecular mechanisms that control cell-state transitions in cancer.

Cancer development is shaped not only by mutations, but also by the ability of cells to acquire abnormal identities and maintain or change those states during progression and treatment. Our lab investigates how pathological cell states arise, how they become stably encoded, and how they can be reversed or therapeutically targeted.

We are looking for a highly motivated scientist with expertise in areas such as molecular biology, biochemistry, chromatin biology, epigenetics, or cancer cell biology.

Located in Boston and the surrounding communities, Dana-Farber Cancer Institute is a leader in life changing breakthroughs in cancer research and patient care. We are united in our mission of conquering cancer, HIV/AIDS, and related diseases. We strive to create an inclusive, diverse, and equitable environment where we provide compassionate and comprehensive care to patients of all backgrounds, and design programs to promote public health particularly among high-risk and underserved populations.

We conduct groundbreaking research that advances treatment, we educate tomorrow's physician/researchers, and we work with amazing partners, including other Harvard Medical School-affiliated hospitals.

Research Areas

Our group studies cell-state regulation across the natural history of gastrointestinal cancer through several complementary programs:

Premalignant cell-state control

Investigating how APC-mutant cells acquire regenerative and oncofetal identities, and how developmental transcription factors such as SOX9 recruit chromatin-remodeling machinery during tumor initiation.

Metabolic regulation of cellular identity

Defining how retinoic acid metabolism and environmental exposures reshape differentiation and establish long-lasting cancer-promoting states.

Therapeutic targeting of plasticity

Identifying strategies to force tumor differentiation or prevent

Transitions into drug-resistant states.

Scientific Environment

The incoming fellow will join the lab at a strong and exciting stage. Significant mechanistic groundwork, model systems, reagents, and preliminary observations are already in place, while major biological questions remain open.

We anticipate 6–18 months of overlap with experienced senior investigators , allowing for substantial transfer of technical expertise and project continuity while the new fellow develops independent scientific ownership.

The lab sits at the intersection of:

basic molecular biology human cancer genetics translational oncology therapeutic discovery within the scientific communities of Dana-Farber, Harvard Medical School, and the Broad Institute .

Potential Project Areas

Possible projects include:

• Transcription factor–chromatin remodeler biochemistry
• Elucidating how transcription factors such as SOX9 interact with BAF/SWI-SNF chromatin-remodeling complexes, including domain requirements, intrinsically disordered regions, complex assembly, and chromatin recruitment.
• Programmable control of chromatin and cell state
• Developing approaches that leverage transcription factor recruitment modules to manipulate endogenous chromatin and cellular identity.
• Retinoid metabolism and differentiation
• Studying how epithelial injury alters vitamin A/retinoic acid metabolism, identifying relevant metabolites and receptors, and testing whether differentiation can be restored in premalignant settings.
• Mechanisms of cancer-cell plasticity
• Determining how tumor cells shift among differentiated, secretory, regenerative, and fetal-like states during oncogenic signaling and targeted therapy.
• Translational cell-state biology
• Validating mechanisms in patient-derived organoids, premalignant human specimens, genetically engineered mouse models, xenografts, and other physiologically relevant systems.
• Experimental Approaches
• Research in the laboratory includes: protein biochemistry co-immunoprecipitation proteomics transcription factor biology
• CRISPR-based engineering degron systems chromatin profiling reporter assays organoid biology microscopy functional genetic screens drug perturbation studies genetically engineered mouse models genome-scale and single-cell analysis
• Candidate Qualifications
• We seek an intellectually ambitious and rigorous scientist with a: Ph.D., M.D., or M.D./Ph.D.
• strong training in experimental biology demonstrated creativity, scientific judgment, and ability to work independently
• Preferred Experience
• Candidates may have experience in one or more of the following: molecular biology and protein biochemistry transcription factor biology chromatin remodeling or epigenetics protein–protein interactions cell signaling and cancer biology
• CRISPR-based genetic engineering organoid or stem cell biology quantitative cell biology or microscopy in vivo studies synthetic biology

Expertise in every area is not required . Candidates with strong mechanistic thinking, experimental rigor, and the ability to learn quickly will be highly competitive, even if their previous research system differs from ours.

Experience with mouse models is a plus.

What We Value

We are especially interested in scientists who are:

deeply curious about biological mechanism rigorous, but willing to take conceptual risks collaborative and generous with colleagues eager to learn beyond their original discipline motivated to translate fundamental biology into insights that may ultimately improve cancer prevention or treatment

Our goal is not simply to describe cancer-associated cell states, but to determine how they are built, why they persist, and how they can be controlled .

Responsibilities

• The postdoctoral fellow will: design and execute independent experiments analyze and interpret data develop mechanistic hypotheses collaborate with computational and translational scientists prepare manuscripts and scientific presentations contribute to grant development help mentor junior laboratory members
• Application Instructions
• Applicants should submit the following materials to: pui_lie@dfci.harvard.edu nilay_sethi@dfci.harvard.edu
• Required Materials
• Curriculum vitae (CV)
• Brief cover letter describing prior work, scientific interests, and potential areas of interest in the lab
• (maximum 2 pages)
• Names and contact information for three references
• (must include Ph.D. advisor)
• Additional Information
• Applications will be reviewed on a rolling basis
• Start date is flexible
• At Dana-Farber Cancer Institute, we work every day to create an innovative, caring, and inclusive environment where every patient, family, and staff member feels they belong. As relentless as we are in our mission to reduce the burden of cancer for all, we are committed to having faculty and staff who offer multifaceted experiences. Cancer knows no boundaries and when it comes to hiring the most dedicated and compassionate professionals, neither do we. If working in this kind of organization inspires you, we encourage you to apply.
• Dana-Farber Cancer Institute is an equal opportunity employer and affirms the right of every qualified applicant to receive consideration for employment without regard to race, color, religion, sex, gender identity or expression, national origin, sexual orientation, genetic information, disability, age, ancestry, military service, protected veteran status, or other characteristics protected by law.
• EEO Poster
• . Pay Transparency Statement
• The hiring range is based on market pay structures, with individual salaries determined by factors such as business needs, market conditions, internal equity, and based on the candidate’s relevant experience, skills and qualifications.

For union positions, the pay range is determined by the Collective Bargaining Agreement (CBA).

$72,000.00 - $76,385.00