Jieya Shao, PhD

• Mechanistic study of novel anticancer targets
• DNA damage response
• Chemotherapy resistance
• Endocrine therapy resistance

Our lab is interested in mechanism-based translational research. We are particularly interested in understanding the biology of novel cancer targets with known clinical relevance but poorly understood molecular mechanisms. We believe by pursuing this type of research we may open doors to new therapeutic opportunities to complement the existing treatments. Currently we are focusing on two main projects in the context of breast cancer.

1. “Moonlighting” functions of the actin-binding protein profilin-1 (Pfn1) in transcriptional and epigenetic regulation
   As an essential eukaryotic protein, the mechanisms behind the paradoxical anticancer effects of profilin-1 have remained mysterious for nearly two decades. Our recent studies suggest that the anticancer activities of Pfn1 may stem from its poorly understood nuclear functions which become deregulated in cancer due to an alteration of its nucleocytoplasmic trafficking. We are currently focusing on defining its novel roles in transcriptional control and epigenetic regulation in the context of both estrogen receptor positive and triple negative breast cancer by utilizing multidisciplinary approaches including biochemistry, molecular and cellular biology, proteomics, mouse xenograft models, and next generation sequencing.
2. The role of VCP in protein homeostasis, DNA damage response, and chemotherapy efficacy of cancer
   Valosin-containing protein (VCP) is an evolutionarily conserved and highly abundant AAA+ ATPase involved in diverse cellular processes. Functioning as a “segregase”, VCP maintains protein homeostasis by extracting polyubiquitinated proteins from various cellular locations or complexes for turnover. Numerous studies have now linked VCP to chromatin-associated protein degradation and genome stability maintenance particularly in the context of DNA damage response. Nevertheless, detailed understanding of its mechanism of action, its mode of (de)regulation in cancer, and its relevance to chemotherapy response is lacking, and we are currently investigating all these questions.