Research excellence transforming patient care
David Crowe, DDS, PhD
The ends of our chromosomes (telomeres) shorten each time our cells divide. Therefore as we age our telomeres become shorter, normally leading our cells to stop dividing. Our telomere length is set early during development, but cellular stresses such as tobacco use and sun exposure can shorten telomeres. Short telomeres have been associated with a variety of age related diseases including cancer. The reverse transcriptase telomerase can extend the ends of chromosomes resulting in increased cellular lifespan, which is important for highly proliferative tissues such as mucosa, epidermis, and bone marrow. However, most cancer cells also express telomerase which promotes progression of tumors. Our laboratory has shown that premalignant cells short circuit a key mechanism by which cells differentiate leading to increased telomerase expression. We also have shown that head and neck cancers with short telomeres are significantly associated with metastasis, which results in poor prognosis for these patients. These metastatic cells have characteristics of cancer stem cells, which are critical for initiating tumors at these distant sites. Using a variety of transgenic models and patient tumor tissues, our laboratory is engaged in understanding how stem cells regulate their telomere length and how disrupted telomere maintenance can lead to tumor formation and metastasis.
Bojovic B, Crowe DL. 2012. Dysfunctional telomeres promote genomic instability and metastasis in the absence of telomerase activity in oncogene induced mammary cancer. Mol Carcinogenesis, in press
Bojovic B, Crowe DL. 2011. Telomere dysfunction promotes metastasis in a Terc null mouse model of head and neck cancer. Mol Cancer Res 9:901-913
Bojovic B, Crowe DL. 2011. Resistance to telomerase inhibition by human squamous cell carcinoma cell lines. Int J Oncol 38:1175-1181
Tsai LN, Ku TKS, Salib N, Crowe DL. 2008. Extracellular signals regulate rapid coactivator recruitment at AP-1 sites by altered phosphorylation of both CREB binding protein (CBP) and c-jun proteins. Mol Cell Biol 28:4240-4250
Ku TKS, Nguyen DC, Karaman M, Gill P, Hacia JG, Crowe DL. 2007. Loss of p53 expression correlates with metastatic phenotype and transcriptional profile in a new mouse model of head and neck cancer. Mol Cancer Res 5:351-362
Chuang R, Crowe DL. 2007. Understanding genetic progression of squamous cell carcinoma to spindle cell carcinoma in a mouse model of head and neck cancer. Int J Oncol 30:1279-1287.
Masood R, Kumar SR, Sinha UK, Crowe DL, Krasnoperov V, Reddy RK, Zozulya S, Singh J, Xia G, Broek D, Schnthal AH, Gill PS. 2006. EphB4 provides survival advantage to squamous cell carcinoma of the head and neck. Int J Cancer 119(6):1236-48.
Crowe DL, Sinha UK. 2006. p53 apoptotic response to DNA damage dependent on bcl2 but not bax in head and neck squamous cell carcinoma lines. Head Neck 28:15-23.
Ku TK, Crowe DL. 2007. Coactivator-mediated estrogen response in human squamous cell carcinoma lines. J Endocrinol 193(1):147-55.
Conway WC, Van der Voort van Zyp J, Thamilselvan V, Walsh MF, Crowe DL, Basson MD. 2006. Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion. J Cell Biochem 15;98(6):1507-16.
Find out more
- UIC Research Resource Center (RRC)
- UIC Biologic Resource Laboratory (BRL)
- UIC Center for Clinical and Translational Sciences (CCTS)
- Tissue Bank/ Transdisciplinary Pathology
- Chicago Biomedical Consortium
- Library Research Resources and Clinical Tools for Dentistry
- National Institute of Craniofacial and Dental Research