Faculty
Adam B. Glick
Associate Professor of Veterinary & Biomedical Sciences
306C Life Sciences Building
Telephone: 814-865-7170
FAX: 814-863-1696
Email: abg11@psu.edu
Research Focus
My laboratory is focused on understanding the signaling pathways controlling squamous cancer formation in the skin in order to shed light on mechanisms of cancer development and to identify potential targets for new anti-cancer therapies. Nonmelanoma skin cancer is increasing in the United States at alarming rates due to higher UV light exposure. In addition the long term immunosuppression required for organ transplantation results in highly aggressive recurrent cutaneous squamous cell carcinoma.
We use the multistage mouse skin carcinogenesis model to understand mechanisms of cancer formation. In this model cancers are generated in the skin of mice by topical application of carcinogens and repeated exposure to chemicals that cause outgrowth of benign tumors, some of which eventually progress to malignant squamous cell carcinomas. The mouse epidermis serves as a useful model for human cancers since most solid tumors form in epithelial tissues, are frequently the result of some type of environmental or physical carcinogen exposure and progress though multiple stages. Due to the superficial nature of the mouse skin tumors, the different stages can be easily quantitated and manipulated. My lab is specifically focused on the TGF1 (transforming growth factor beta-1) signaling pathway and its role in skin cancer development. TGF1 is a growth factor secreted by normal and neoplastic cells that has multiple biological effects on epithelial, mesenchymal and immune cells. It has a unique property of being a negative regulator of cell growth, and many human cancers are no longer responsive to TGF1 due to specific mutations in the signaling pathway. However, many human cancers produce high levels of TGF1 which affect the immune system and the normal cells surrounding the tumor in a way that favors tumor growth. Thus TGF1 can have both tumor suppressive and tumor promoting activities depending on tumor stage and tissue context. We utilize several transgenic and knockout models to alter TGF1 signaling in vivo and in vitro and determine how this impacts cancer development. We are particularly interested in what causes TGF1 action to switch from tumor suppressor to tumor promoter and have focused on how TGF1 production by normal and tumorigenic epithelial cells impacts the anti-tumor immune response, and how TGF1 signaling interacts with oncogenic pathways such as ras and HPV E6/E7 to suppress or enhance the malignant phenotype.
Publications
- Morris, D.G., Huan, X., Kaminski, N., Wang, Y., Shapiro, S.D., Dolganov, G., Glick, A., and Sheppard, D. Loss of integrin-mediated TGF activation causes Mmp12-dependent pulmonary emphysema. Nature 422:169-173, 2003.
- Vijayachandra, K., Lee, J., and Glick, A. Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model. Cancer Research 63: 120-123, 2003.
- Liu, X., Lee, J., Cooley, M., Alexander, V., Bhogte, E., Hartley, S. and Glick, A. Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion in a mouse model for squamous cell carcinoma. Cancer Research 63: 7760-7768, 2003.
- Glick, A. TGF1 Back to the Future: Revisiting its Role as a Transforming Growth Factor Cancer Biology and Therapy 3: 276-283, 2004.
- Woodworth, C.D., Michael, E., Smith, L., Vijayachandra, K., Glick, A., Hennings, H.
and Yuspa, S. Strain dependent differences in malignant conversion of mouse skin tumors is an inherent property of the epidermal keratinocyte. Carcinogenesis 25: 1771-1778, 2004.
- Chu, E. Y., Hens, J., Andl, T., Kairo, A., Yamaguchi, T. P., Brisken, C., Glick, A., Wysolmerski, J. J., and Millar, S. E. Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131: 4819-4829, 2004.
- Sauer, B., Vogler, R., von Wenkstern, H., Fujii, M., Anzano, M.M., Glick, A.B., Schaffer-Korting, M., Roberts, A.B., and Kleuser, B. Involvement of Smad signaling in sphingosine 1-phosphate-mediated biological responses of keratinocytes. J. Biol. Chem. 279:38471-38479, 2004.
- Glick, A. TGF1 Back to the Future: Revisiting its Role as a Transforming Growth Factor. Cancer Biology and Therapy 3: 276-283, 2004.
- Woodworth, C., Smith, M., Vijayachandra, K., Glick, A, Hennings, H. and Yuspa S. Strain dependent differences in malignant conversion of mouse skin tumors is an inherent property of the epidermal keratinocytes. Carcinogenesis 25: 1771-1778, 2004.
- Hutchin, M; Kariapper, M., Gratchouk, M., Wang, A., Wei, L., Cummings, D., Liu, J., Michael, E., Glick, A., and Dlugosz, A. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes and Development 19: 214-223, 2005.
- Glick, A. and Yuspa S.H. Tissue homeostasis and the control of the neoplastic phenotype in epithelial cancers. Seminars in Cancer Biology 15: 75-83, 2005.
- Suh, K.S., Muto, M., Gerdes, M., Crutchley, J.M., Mutoh, T., Edwards, L.E., Dumont, R.A., Sodha, P., Cheng, C., Glick, A. and Yuspa, S.H. Antisense suppression of the CLIC family induces apoptosis, enhances TNF-induced apoptosis and inhibits tumor growth. Cancer Research 65: 562-571, 2005.
- Abdel-Fattah R, Glick A, Rehman I, Maiberger P, Hennings H. Methylation of the O(6)-methylguanine-DNA methyltransferase promoter suppresses expression in mouse skin tumors and varies with the tumor induction protocol. Int J Cancer. 118:527-31, 2006.
- Gerdes MJ, Myakishev M, Frost NA, Rishi V, Moitra J, Acharya A, Levy MR, Park SW, Glick A, Yuspa SH, Vinson C. Activator protein-1 activity regulates epithelial tumor cell identity. Cancer Research. 66:7578-88, 2006.
- Kirshner J, Jobling MF, Pajares MJ, Ravani SA, Glick AB, Lavin MJ, Koslov S, Shiloh Y, Barcellos-Hoff MH. Inhibition of transforming growth factor-beta1 signaling attenuates ataxia telangiectasia mutated activity in response to genotoxic stress. Cancer Res. 2006 66:10861-10869. 2006.
- Darwiche N, Ryscavage A, Perez-Lorenzo R, Wright L, Bae DS, Hennings H, Yuspa SH, Glick AB. Expression profile of skin papillomas with high cancer risk displays a unique genetic signature that clusters with squamous cell carcinomas and predicts risk for malignant conversion. Oncogene, 2007.