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David Kusner


david-m-kusner@uiowa.edu
Mentor: Weizhou Zhang, Ph.D.
Lab Room: 1035 ML
Lab Phone: 319-335-6832

ROR1 in basal type breast cancer

Being the second leading cause of death in women within the United States, breast cancer remains a major problem. Triple negative breast cancer (with ~70% overlap with basal type), defined by the lack of estrogen receptor (ER), progesterone receptor (PR), or HER2 expression, is one of the most aggressive types of breast cancer and remains the only molecular subtype of breast cancer in which there is no targeted therapy available. Receptor tyrosine kinase orphan receptor 1 (ROR1) is a single pass transmembrane protein that is expressed in a variety of cancer and is associated with their progression. Our lab, among others, identified the specific expression of ROR1 in basal type breast cancers. Using this knowledge, we hope to understand the role of ROR1 in breast cancer.

My research will include the examination and characterization of ROR1 tumorigenesis and progression in transgenic mice in an MMTV-ErbB2 breast cancer model. Utilizing luminal and basal promoter driven expression of ROR1 will allow us to examine ROR1 more specifically in the context of tumor initiation and progression. Additionally, an anti-ROR1 immunotoxin will be tested as a triple negative breast cancer-specific therapeutic within breast cancer mouse models. Interesting, we identified a connection between ROR1 and EGFR signaling pathway. ROR1 is important for EGF-induced duration of AKT activation, having little impact on initial activation of AKT. We will further implore the molecular mechanism how ROR1 potentiates EGF/EGFR signaling in the context of human triple negative breast cancer. The proposed studies will help to identify a novel regulatory component in the EGFR network and provide rationale for targeting ROR1 to treat triple negative breast cancer.