About Us

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Age is the most significant risk factor for cancer development. While it is clear that cell autonomous mutations are integral to the transformation process, it has become increasingly evident that changes in the surrounding, ostensibly normal stroma drive the transformation process and tumor progression. Indeed, stromal cells isolated from a tumor (but not normal tissue) can stimulate tumor formation and progression by altering the microenvironment in profound ways including directly modulating the local immune response and changing the tissue parenchyma.  Senescent (i.e. “aged”) fibroblasts function analogously by activating similar mechanisms including stabilizing mRNAs (collectively referred to as the senescence associated secretory pathway, SASP) via activation of the p38MAPK-MK2 pathway. The laboratory is utilizing it’s discovery of these pathways and novel models to understand how changes in the stromal compartment contribute to tumor progression.  Some of the current areas of interest include: 1) elucidating how senescent stromal cells alter the premetastatic niche and drive increases in bone metastasis; 2) delineating how the SASP alters the immune response to established tumors and asking if we can target these changes to limited tumor progression; 3) establishing how the SASP contributes to chemotherapy-induced bone loss (it isn’t all estrogen); 4) examining the role SASP plays in establishing a chemoprotective niche inside that bone where latent tumor cells lurk sometimes for years before emerging as life threatening lesions and 5) determining how the SASP impacts a tumor cells ability to enter/exit dormancy.  To accomplish our goals we use a wide variety of in vitro and in vivo mouse models. 

Ongoing Projects --- Rotation Possibilities

1. Elucidating the senescent stromal mechanisms that alter the local immune response and increase tumorigenesis.
2. Determining how senescence contributes to pathological bone loss in chemotherapy treated patients
3. Examining how dormant versus proliferating tumor cells interact with the bone surface --- a multi-modal imaging approach with the WUCCI.  Imaging tumor cells in a living bone and following their fate over time.
4. Determining the role senescent stormal versus epithelial cells play in a spontaneous model of breast cancer metastasis.
5. Building a better mouse trap to interrogate the impact of aging stroma in breast cancer.
6. Investigating the role tissue density around aging stromal cells plays in tumorigenesis
7. Pre-clinical studies on the feasibility of p38MAPK and MK2 inhibitors in metastatic breast cancer patients.