Bonnie Hylander, PhD
Working in a Comprehensive Cancer Center has focused my attention on the need to improve the efficacy of cancer treatments because even though many patients see substantial long-term benefits, many do not. Ultimately my goal is to understand mechanisms of resistance and ways to sensitize tumors to different therapeutics. For this, it is imperative to have relevant, reliable, reproducible mouse models. I have extensive experience with a variety of mouse tumor models including syngeneic, orthotopic, metastatic, chemically induced and xenograft (both cell lines and patient derived) models. I also have extensive experience in tumor histology and analyzing parameters of tumor growth by immunohistochemistry (e.g. vascularization, proliferation, and apoptosis).
It is becoming clear that both the growth and response to therapy of tumors in pre-clinical mouse models is affected by external factors which can impact the physiology of the mouse and experimental outcomes. In particular, working with Dr. Elizabeth Repasky, I have become interested in how mandated environmental factors, such as housing temperature, affect levels of stress hormones. This exciting new research direction is the result of our discoveries that tumor-bearing mice at standard housing temperatures (22˚C) experience chronic cold stress which promotes 1) tumor growth, 2) immune suppression and 3) resistance to cytotoxic therapies. Furthermore, these negative effects of stress are mediated by cold induced elevation in norepinephrine and can be reversed by housing mice at 30˚C or treating them with a β-adrenergic receptor antagonist, resulting in enhanced anti-tumor immune responses and sensitivity to cytotoxic therapy. Thus, a major focus of our research is developing strategies for combining standard therapies and new therapies, such as immunotherapies, with β-adrenergic receptor blockade.
Other areas of interest are the biology and therapeutic targeting of cancer stem cells, the development of patient derived xenograft models for testing of therapies and biomarker discovery, and approaches to improved delivery of therapies to the tumor.