Professor in Surgery/Urology
K6/561 Clinical Sciences Center
Research Interests: Human Development/Teratogenicity. Prostate. Sonic Hedgehog. BMP-4. Inhibition of tumor growth by cyclopamine, and Shh signaling as a therapeutic target in prostate cancer.
Work in my laboratory is focused on the regulation of growth during normal prostate development and the reactivation of developmental pathways in prostatic neoplasia. Working in the mouse, we are examining the role of the Sonic hedgehog (Shh) signaling pathway and Bone Morphogenetic Protein –4 (BMP-4) in the mesenchymal-epithelial signaling that regulates prostate ductal budding. We are studying the role of Hh signaling in prostate cancer and, using a xenograft tumor model, we have shown that activation of Shh signaling increases stromal Gli gene expression and – by a paracrine mechanism – significantly accelerates tumor growth. These observations suggest that the Shh pathway may be a critically important pathway in allowing tumor cells to recruit the host stromal cells to support tumor growth. Recently, our laboratory has successfully isolated and grown prostate stem cells in culture and we are pursuing studies aimed at elucidating the role of Shh and BMP signaling in stem cell maintenance and proliferation. Finally, we have developed a mouse model of chronic prostate inflammation and are studying the role of inflammatory mediators in the development of reactive hyperplasia and prostate cancer.
- Lipinski RJ, Bijlsma MF, Gipp JJ, Podhaizer DJ, Bushman W. Establishment and characterization of immortalized Gli-null mouse embryonic fibroblast cell lines. BMC Cell Biol. 2008 Sep 13;9:49
- Lipinski, R.J., Hutson, P.R., Hannam, P.W., Nydza, R.J., Washington, I.M., Moore, R.W., Girdaukas, G.G., Peterson, R.E. and Bushman, W.: Dose- and route-dependent teratogenicity, toxicity, and pharmacokinetic profiles of the Hedgehog signaling antagonist cyclopamine in the mouse. Toxicol. Sci. 104: 189-197, 2008.
- Bruxvoort KJ, Charbonneau HM, Giambernardi TA, Goolsby JC, Qian CN, Zylstra CR, Robinson DR, Roy-Burman P, Shaw AK, Buckner-Berghuis BD, Sigler RE, Resau JH, Sullivan R, Bushman W, Williams BO. Inactivation of apc in the mouse prostate causes prostate carcinoma. Cancer Res. 2007 Mar 15;67(6):2490-6.
- Gipp J, Gu G, Crylen C, Kasper S, Bushman W.Hedgehog pathway activity in the LADY prostate tumor model.Mol Cancer. 2007 Mar 7;6:19.
- Zhang J, Lipinski R, Shaw A, Gipp J, Bushman W.Lack of demonstrable autocrine hedgehog signaling in human prostate cancer cell lines. J Urol. 2007 Mar;177(3):1179-85.
Mentor to METC Graduate Students:
- Bayli Boehm (MS 2009)
- Rob Lipinski (2008)
- Letitia Wong (2014)
- Min Yu (2010)
Mentor to METC Post-Docs:
- Travis Jerde, PhD (2006-2007; 2009-2010)