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.
Hylander, B.L., Pitoniak, R., Penetrante, R.B., Gibbs, J.F., Oktay, D., Cheng, J. & Repasky, E.A. The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown as xenografts in SCID mice. J Transl Med 3, 22. (2005).
Hylander, B.L., Punt, N., Tang, H., Hillman, J., Vaughan, M., Bshara, W., Pitoniak, R. & Repasky, E.A. Origin of the vasculature supporting growth of primary patient tumor xenografts. J Transl Med 11, 110 (2013).
Eng, J.W., Reed, C.B., Kokolus, K.M., Pitoniak, R., Utley, A., Bucsek, M.J., Ma, W.W., Repasky, E.A. & Hylander, B.L. Housing temperature-induced stress drives therapeutic resistance in murine tumour models through beta-adrenergic receptor activation. Nat Commun 6, 6426 (2015).
Hylander, B.L., Sen, A., Beachy, S.H., Pitoniak, R., Ullas, S., Gibbs, J.F., Qiu, J., Prey, J.D., Fetterly, G.J. & Repasky, E.A. Tumor priming by Apo2L/TRAIL reduces interstitial fluid pressure and enhances efficacy of liposomal gemcitabine in a patient derived xenograft tumor model. J Control Release 217, 160-169 (2015).
Hylander, B.L. & Repasky, E.A. Thermoneutrality, Mice and Cancer: A Heated Opinion. Trends in Cancer 2(2016).
Hylander, B.L., Eng, J.W. & Repasky, E.A. The Impact of Housing Temperature-Induced Chronic Stress on Preclinical Mouse Tumor Models and Therapeutic Responses: An Important Role for the Nervous System. Adv Exp Med Biol 1036, 173-189 (2017).
Hylander BL, Repasky EA: Thermoneutrality, Mice and Cancer: A Heated Opinion Trends in Cancer 2016 (in press).
Hylander BL, Sen A, Beachy SH, Pitoniak R, Ullas S, Gibbs JF, Qiu J, Prey JD, Fetterly GJ, Repasky EA: Tumor priming by Apo2L/TRAIL reduces interstitial fluid pressure and enhances efficacy of liposomal gemcitabine in a patient derived xenograft tumor model. Journal of controlled release : official journal of the Controlled Release Society 2015, 217:160-169.
Eng JW, Reed CB, Kokolus KM, Pitoniak R, Utley A, Bucsek MJ, Ma WW, Repasky EA, Hylander BL: Housing temperature-induced stress drives therapeutic resistance in murine tumour models through beta2-adrenergic receptor activation. Nature communications 2015, 6:6426.
Sharma R, Buitrago S, Pitoniak R, Gibbs JF, Curtin L, Seshadri M, Repasky EA, Hylander BL: Influence of the implantation site on the sensitivity of patient pancreatic tumor xenografts to Apo2L/TRAIL therapy. Pancreas 2014, 43(2):298-305.
Kokolus KM, Capitano ML, Lee CT, Eng JW, Waight JD, Hylander BL, Sexton S, Hong CC, Gordon CJ, Abrams SI, Repasky EA: Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature. Proc Natl Acad Sci U S A 2013, 110(50):20176-20181.
Hylander BL, Punt N, Tang H, Hillman J, Vaughan M, Bshara W, Pitoniak R, Repasky EA: Origin of the vasculature supporting growth of primary patient tumor xenografts. J Transl Med 2013, 11(1):110.
Sugamura K, Gibbs JF, Belicha-Villanueva A, Andrews C, Repasky EA, Hylander BL: Synergism of CPT-11 and Apo2L/TRAIL against two differentially sensitive human colon tumor xenografts. Oncology 2008, 74(3-4):188-197.