Kelli Valdez, PhD

Research Assistant Professor, Division of Cancer and Developmental Biology

Current Research Focus:
Development of a human DCIS progression model by the MIND method

My primary project is to develop and validate the mouse intraductal model (MIND) of human DCIS by intraductal transplantation of primary human DCIS cells into mice, which will allow for characterization of invasion potential and development of subtype-specific therapies. Our central hypothesis is that there are subtypes of DCIS arising from distinct subpopulations of tumor initiating cells, and that these subpopulations have differing potentials for malignant progression. This hypothesis is based on previous studies using surface markers unique to normal human breast basal and luminal progenitor cells, as well as human breast cancer tumor initiating cells, to isolate and assess their in vivo growth and self-renewal potential. My specific aims are to 1) demonstrate the stability of the MIND xenograft model by sequential transplantation of human primary DCIS cells; and 2) characterize the signaling pathways, such as Notch, Wnt, Hedgehog, and Bmi-1, potentially involved in growth, self-renewal, and invasion of primary human DCIS cells using the MIND model. This will enable future pathway-focused studies will be extended to the discovery of molecular mechanisms underlying invasive progression in the xenograft lines that we plan to develop from primary human DCIS.

MIND model:Human DCIS cells are present in ducts of injected mouse mammary glands

Immunofluorescent staining of human cytokeratin 5 (K5), smooth muscle actin, and DNA in mouse mammary glands injected intraductally with primary human DCIS.  K5 is a marker of basal types of DCIS.