Karen M. Bussard, MS, PhD
Associate Professor
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Karen M. Bussard, MS, PhD
Associate Professor
Education
PhD, Pathobiology, The Pennsylvania State University, 2008
MS, Biomedical Engineering, The Pennsylvania State University, 2002
BS, Biology, Fairleigh Dickinson University, 1999
Most Recent Peer-Reviewed Publications
- A Representative Clinical Course of Progression, with Molecular Insights, of Hormone Receptor-Positive, HER2-Negative Bone Metastatic Breast Cancer
- Stromal-derived extracellular vesicles suppress proliferation of bone metastatic cancer cells mediated by ERK2
- Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts
- Extracellular Vesicles and Bone-Associated Cancer
- Combined targeting of PARG and wee1 causes decreased cell survival and DNA damage in an S-phase–dependent manner
Research Interests
Breast cancer has a predilection for bone metastases, and is the second leading cause of cancer deaths in American women. While the mechanism for directional metastasis is unknown, the bone microenvironment provides a fertile soil for breast cancer cells to colonize and grow.
Metastatic lesions are thought to originate from disseminated tumor cells (DTCs) shed from a primary tumor. Clinical evidence suggests that, upon entry in a secondary niche, DTCs undergo proliferative quiescence for a period of up to 25 years, where they are capable of escaping immune surveillance and evading chemotherapeutic agents. As a result, breast cancer patients successfully treated for primary breast cancer decades before suddenly develop overt macrometastases without prior symptoms. This latency period before relapse at a secondary site can be defined as metastasis dormancy. Thus, there is a critical need for elucidating the molecular mechanisms facilitating breast cancer dormancy and reactivation in the bone such that preventative therapeutics can be developed. Despite the high prevalence of dormant tumors in humans, this area of cancer research is poorly understood and understudied.
The focus of Dr. Bussard’s research is two-fold: 1) identify microRNA, proteins, and novel mediators that facilitate cancer cell dissemination to bone, including mediators of cancer cell arrival and localization, as well as delineate conditions that orchestrate proliferative quiescence and cancer cell re-activation in bone. Data generated in Dr. Bussard’s laboratory suggest that osteoblasts form gap junctions with metastasis-suppressed breast cancer cells, which may contribute to cellular crosstalk between the two cell types. Bone osteoblasts were also found to produce exosomes which contain exosomal microRNAs found to be involved in cell cycle control and cellular dormancy. These osteoblast-derived exosomes were taken up by breast cancer cells in a co-culture setting.
In parallel, 2) research in Dr. Bussard’s laboratory intends to elucidate the molecular basis of crosstalk between tumor cells and the host stroma, with a focus on understanding alterations in bone osteoblasts, that create a permissible environment for metastatic cancer cell colonization and survival. Dr. Bussard has found that breast cancer cells cause osteoblasts to alter their production of matrix proteins, and increase their production of a set of inflammatory cytokines: IL-6, IL-8, MCP-1, and VEGF that mediate breast cancer cell maintenance and survival. Combined, these data suggest that there is extensive crosstalk between osteoblasts and disseminated cancer cells in bone, and highlights the importance of investigating osteoblasts as key players which mediate cancer cell proliferative quiescence in bone.
Research in Dr. Bussard’s laboratory utilizes both 2D and 3D in-vitro cell culture models, high-end fluorescence microscopy, novel humanized mouse models of tumor development, and implantable hydrogel biomaterial scaffolds to examine interactions between cancer cells and the host stroma, with a focus on bone metastatic breast cancer. Dr. Bussard is also the recipient of a NIH/NCI K99/R00 Pathway to Independence Award, which has been instrumental to establishing her research program.