Research Projects

The translational research program in the Schiff-Osborne lab, is primarily focused on the estrogen receptor (ER) and the HER2 signaling pathways in breast cancer, with the major objectives of exploring key oncogenic/signaling networks, developing biomarkers to design tailored targeted therapies, and identifying the mechanisms responsible for resistance against targeted treatments. Through integrative OMICS and functional genomics using preclinical cell line and tumor models, and clinical specimens, we strive to identify new therapeutic vulnerabilities.

The specific research projects include:

Estrogen Receptor-Positive Breast Cancer:
• Development and characterization of new clinically relevant preclinical models of resistance to endocrine and other targeted therapies
• Correlative studies using clinical specimens and datasets to identify biomarkers of resistance

Resistance to endocrine therapy
· Evaluate the importance and role of the pioneer factor FOXA1 in endocrine resistance and metastasis
· Characterization of genetic aberrations in FOXA1
· Assess the role of transcriptional reprogramming and epigenomics in endocrine resistance and metastasis

Resistance to CDK4/6 inhibitors
· Study the role of tumor cell interferon signaling in intrinsic and acquired resistance
· Explore the role of MEK/MAPK signaling in resistance

HER2-Positive Breast Cancer:
• Development and characterization of new clinically relevant preclinical models of resistance to HER2-targeted therapies
• Correlative studies using clinical specimens to develop biomarkers of response to anti-HER2 therapy

Tailored and de-escalated treatment strategies
· Evaluate the potency of new drugs against HER2
· Explore novel combinations of different clinically relevant anti-HER2 agents

Resistance to HER2-targeted therapy
· Incidence and role of ERBB2 mutations in conferring anti-HER2 resistance
· Study the role of metabolic vulnerabilities as alternative pathways in HER2-targeted therapy resistance
· Cross-talk with transcription factors in treatment resistance (e.g., estrogen receptor)
· Explore the role of cell surface components in conferring resistance (e.g., integrins, mucins)
· Explore additional novel mechanisms of resistance