Research

Establishment of cellular and molecular events that occur during mammary gland development

The majority of information regarding human mammary gland development is extrapolated from humanized rodent models. However, the pig mammary gland more closely represents human mammary gland structure compared to mouse and rat models, and the pig model does not require surgical intervention with the intention to evaluate development that mimics human profiles. Difficulty exists in studying abnormal mechanisms during diseases states such as cancer when normal progression of tissue development is unknown.  In order to investigate cellular perturbations that occur in breast cancer, the need remains to fully understand mammary gland development from a non-diseased model. Utilizing the Dunn Biopsy Method, we evaluate pig mammary tissue shortly after birth through development in order to understand mechanisms that lead to diseased states in breast cancer. The long-term goal is to develop a full array of mammary gland tissue samples that will provide a robust dataset of morphological images and genetic expression data to aid in understanding molecular events that occur during development.

Evaluation of ECM remodeling and the effects on EMT during breast cancer progression

Previous research by our group has identified genetic homology between early developmental signaling events in pig models compared to breast cancer profiles in humans. This innovative methodology carries the potential to define novel biomarkers involved in early development and diseased states such as breast cancer.  Utilizing laser microdissection, morphological areas of interest in selected breast cancer tumors can be extracted from the remaining tissue for further downstream analysis. This method provides a technique to evaluate human tumor samples based on tumor stage, grade, and breast cancer subtype compared to healthy developing pig models. Candidate targets are validated in cancer cell models and tumor xenografts in mice with gain- and loss-of-function assays. The long-term goal is to evaluate the ECM contribution to carcinogenesis and determine what ECM signals are required to regulate cancer progression.

Investigation of racial disparities associated with the incidence of TNBC

Epidemiological data suggests that African American women are disproportionally affected by breast cancer, they are diagnosed at a younger age, and diagnosed more frequently with an aggressive subtype of breast cancer. Socioeconomic differences between different racial groups was previously attributed to the increased incidence of breast cancer in African American women, however, emerging evidence indicates the tumor microenvironment may render patients to be more susceptible to adverse effects of this disease. The ECM provides a favorable environment for the growth of tumor cells, and the differences in the microenvironment may be the decisive factor for the incidence of breast cancer. Utilizing machine learning techniques, tumors are evaluated for morphological variables with emphasis on the ECM. This technology has the potential to be applied to other racial associated occurrences in tumor prevalence. The long-term goal is to develop an explainable framework from image data and cell population genetic analysis,  which has the potential to determine patient outcomes through identification of breast cancer patients or at-risk individuals.