Pharmacology and Toxicology

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Jay W. Tichelaar, PhD

Assistant Professor
Phone: 414 955-7587
Fax: 414-955-6059

BS - Biology and Microbiology, Minnesota State University, Mankato - 1989
PhD - Biomedical Sciences, Molecular Biology, Mayo Graduate School, Rochester, MN - 1995

Dr. Tichelaar's Faculty Collaboration Database


Research Interest

The focus of my lab is the cellular, molecular and genetic changes that contribute to the process of lung tumorigenesis. Lung cancer is far and away the most common cause of cancer mortality in the US with unacceptably low survival rates. While cigarette smoking is a major environmental risk factor, only 10-15% of smokers will develop lung cancer suggesting individual genetic differences also contribute to the development of this disease. The goal of the research is to identify novel targets for preventive or therapeutic intervention. Both cell culture and genetically engineered mouse models are used.

Function of AP-1 in lung tumorigenesis. AP-1 refers to a family of transcription factors most commonly associated with the proto-oncogenes c-jun and c-Fos but also comprising several other family members. Many studies have demonstrated that proteins of the AP-1 family are elevated in a variety of human tumors, including lung tumors. Recently, we demonstrated that expression of a dominant-negative mutant of c-jun that blocks AP-1 activity inhibits lung tumorigenesis when present in the lungs of mice. Because our mouse model allows us to control the timing of when this mutant protein is present in the lungs, we have been able to demonstrate that even when tumors are allowed to significantly progress, induction of the mutant protein can significantly limit tumor growth. This result suggests that blocking AP-1 activation is an attractive target for intervention even in patients where pre-cancerous lesions may have already developed. Current research is focused on identification of the key gene expression changes mediating the anti-tumor effects of AP-1 inhibition and identifying how they contribute to tumor progression.

Lung Cancer Chemoprevention. Cancer chemoprevention is the use of drugs or botanical agents to prevent the progression or development of cancer, in contrast to chemotherapy which is directed towards the treatment of existing cancer. This approach has great potential to reduce the incidence and mortality of a variety of cancer types. Previous studies in collaboration with Dr. Ming You identified the green tea extract Polyphenon E as an effective agent to prevent the progression of pre-cancerous lesions to cancer in mouse lung. We are currently conducting studies in our dominant negative c-jun mice to determine if Polyphenon E acts in whole or part by inhibiting AP-1 activation. The paradigm of using chemopreventive agents in genetically modified mice can be an important tool for identifying the key pathways used by chemopreventive agents to prevent tumor growth, particularly for complex mixtures such as Polyphenon E. This knowledge has the potential be used to target the identified pathways in a highly specific and effective manner.

Identification of lung cancer susceptibility and/or resistance genes. Recent genome-wide association studies have identified regions of the genome implicated in the development of many diseases including cancer. Once such regions are identified, considerable work remains to identify and validate the causative changes present in these stretches of the genome. One area of our research is to validate lung cancer susceptibility and resistance genes using mouse models. For sporadic lung cancer, susceptibility loci have been identified within chromosomal arms 15q, 5p and 6p. Several mouse models have been obtained that we are testing for altered susceptibility to lung tumor formation. Validation of genes involved in susceptibility and/or resistance to the development of lung cancer may provide entry points for preventive or therapeutic interventions. This knowledge could also be the basis for risk assessment to identify individuals most at risk for developing lung cancer and preferentially targeting this population for chemoprevention.

Selected Publications

Tichelaar JW, Yan Y, Tan Q, Wang Y, Estensen RD, Young MR, Colburn NH, Yin H, Goodin C, Anderson MW, You M. (2010) A dominant-negative c-jun mutant inhibits mouse lung tumorigenesis in vivo. Cancer Prevention Research 3(9):1148-56.

Borchers MT, Wesselkamper SC, Curull V, Ramirez-Sarmiento M, Sanchez-Font A, Garcia-Aymerich J, Coronell C, Lloreta J, Agusti AG, Gea J, Reed MF, Starnes SL, Harris NL, Vitucci M, Eppert BL, Motz GT, Fogel K, McGraw DW, Tichelaar JW, Orozco-Levi M. (2009) Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease. Journal of Clinical Investigation 119(3):636-49.

Anderson MW, Goodin C, Zhang Y, Kim S, Estensen RD, Wiedman TS, Sekar P, Buncher CR, Khoury JC, Garbow JR, You M, Tichelaar JW. (2008) Effect of dietary green tea extract and aerosolized difluoromethylornithine during lung tumor progression in strain A/J mice. Carcinogenesis 29(8):1594-600.

Tichelaar JW, Wesselkamper SC, Chowdhury S, Yin H, Berclaz PY, Sartor MA, Leikauf GD, Whitsett JA. (2007). Duration-dependent cytoprotective versus inflammatory effects of lung epithelial fibroblast growth factor-7 expression. Experimental Lung Research 33:385-417.

Tichelaar JW, Zhang Y, leRiche JC, Biddinger PW, Lam S, Anderson MW. (2005) Increased staining for phosphor-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies. BMC Cancer 5:155.

Perl AK, Tichelaar JW, Whitsett JA. (2002) Conditional gene expression in the respiratory epithelium of the mouse. Transgenic Research 11(1):21-9.

Tichelaar JW, Lu W, Whitsett JA (2000) Conditional expression of fibroblast growth factor-7 in the developing and mature lung. Journal of Biological Chemistry 275(16): 11858-64.
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