Jennifer A Pietenpol, Ph.D.
Professor of Biochemistry
Ingram Professor of Cancer Research
Brock Family Directorship in Career Development
Executive Vice President for Research
Chief Scientific and Strategy Officer
Vanderbilt University Medical Center
Triple negative breast cancer & p53 family proteins
Research Keywords: cancer, triple-negative breast cancer, p53, p63, p73, gene regulation, metabolism
Research Specialty: Mechanistic investigation of epithelial cancers, focusing on triple-negative breast cancer (TNBC) and the transcriptional and signaling pathways controlled by the p53 family.
Research Description and Significance: Most human cancers arise in epithelial tissues, where malignant transformation occurs as cells lose the regulatory controls that normally govern proliferation, differentiation, and genomic stability. As tumor‑suppressor networks fail, particularly those that maintain epithelial identity and genomic integrity, these cancers become genetically diverse and biologically complex. This heterogeneity underscores the critical importance of molecular subtyping to reveal actionable tumor features and guide the development of targeted therapies and prevention strategies.
The laboratory focuses on uncovering the molecular underpinnings of epithelial cancers, with particular emphasis on triple‑negative breast cancer (TNBC) and the signaling pathways controlled by the p53 family of tumor‑suppressor proteins. Over the years, the laboratory has:
- Pioneered advanced approaches to map p53–chromatin interactions and identify p53‑regulated genes
- Demonstrated that p63 signaling drives key epithelial differentiation programs through previously unrecognized transcriptional networks
- Defined functional p73 genomic binding sites and made the seminal discovery that p73 is essential for multiciliogenesis, ovarian folliculogenesis, and regulation of the FoxJ1‑associated gene network, findings that provide new insights into several human inflammatory diseases
- Integrated molecular genetics and bioinformatics to generate the first robust molecular classification of TNBC, identifying the basal-like (BL1 and BL2), mesenchymal (M), and luminal androgen receptor (LAR) subtypes, each with distinct biology, transcriptional diversity, signaling pathways, and therapy responses. This classification framework has been validated and cited extensively, and has informed multiple clinical trials, including NCT00930930, NCT02457910, NCT03206203, and NCT07016399
Current research efforts in the laboratory include:
- Expanding molecular subtyping of TNBC to build a comprehensive breast cancer transcriptomic atlas to refine clinical subtypes
- Preclinical and clinical evaluation of targeted therapies for TNBC, including: (i) identifying biomarkers that predict response or resistance to androgen receptor (AR)–targeted therapies in early‑stage AR+ TNBC, and (ii) developing AR antagonist–resistant TNBC models to evaluate next‑generation selective AR degraders
- Executing multi‑omic investigations to understand TNBC subtype biology and elucidate mechanisms of immune evasion
Postdoctoral Position Availability and Details: Please apply by e-mail to: j.pietenpol@vumc.org