Tumor suppressor genes and oncogenes in human cancer
Dr. Stanbridge's research concerns the molecular genetics of human cancer. In addition to activated oncogenes, a family of genes (called tumor suppressor genes) critically involved in the control of malignancy has been identified. Dr. Stanbridge has provided functional evidence for the role of tumor suppressor genes in human cancer using somatic cell hybrid and monochromosome transfer techniques. His group has also engaged in cloning candidate tumor suppressor genes. One of the functions of such genes appears to be negative regulation of transcription of tumor-associated antigens. One such regulated gene has been identified as carbonic anhydrase 9 (CA9). The encoded protein, CAIX, is in clinical trials for diagnosis and therapy of multiple malignancies, including cervical cancer and renal cancer. CAIX has recently been found to be a marker of hypoxia. The mechanisms underlying this are under investigation.
An important question in the field of cancer molecular genetics is whether there are interactions between tumor suppressor genes and activated oncogenes. Ongoing studies in the laboratory addressing this question involve homologous recombination experiments that disrupt gene function.
Another research interest of Dr. Stanbridge's is to develop molecular probes for the identification of microorganisms in clinical settings. Dr. Stanbridge was one of the early developers of the use of cloned fragments of ribosomal RNA genes as molecular probes for detection of mycoplasmas and other microorganisms in idiopathic diseases such as rheumatoid arthritis where an infectious etiology is suspected.
Liao S.-Y., Rodgers W.H., Kauderer J., Bonfiglio T.A., Darcy K.M., Carter R., Levine L., Spiros N.M., Susumu N., Fujiwara K., Walker J.L., Hatae M., Stanbridge E.J. 2011. Carbonic anhydrase IX (CA-IX) and high risk papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) study. Br J Cancer 104: 353-360.
Cao J., Shafee N., Vickery L., Kaluz S., Ru N., Stanbridge E.J. 2010. Mitogen-activated protein/extracellular signal-regulated kinase kinase 1act/tubulin interaction is an important determinant of mitotic stability in cultured HT1080 human fibrosarcoma cells. Cancer Res. 70: 6004-6014.
Liao, S.Y., Rodgers, W.H., Kauderer, J., Bonfiglio, T.A., Walker, J.L., Darcy, K.M., Carter, R. Levine, L., Spirtos, N.M., and Stanbridge, E.J. 2009. Carbonic anhydrase IX (CA-IX) and human papillomavirus (HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study. 1. United States Study. Int. J. Cancer 125: 2434-2440.
Cheung AKL, Lung HL, Ko JM, Cheng Y, Stanbridge EJ, Zabarovsky ER, Nicholls JM, Chua D, Tsao SW, Guan XY, Lung ML. 2009. Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma. Proc. Natl. Acad. Sci. USA 25: 14478-14483.
Liao, S.Y., Lerman, M.I., and Stanbridge, E.J. 2009. Expression of transmembrane carbonic anhydrases, CAIX and CAXII, in human development. BMC Dev. Biol. 16;9:22
Shafee, N., Kaluz, S., Ru, N., and Stanbridge, E.J. 2009. PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CA9 and VEGF, in human cancer cell lines. Cancer Lett. 282: 109-115.
Shafee, N., Smith, C.R., Wei, S., Kim, Y., Mills, G.B., Hortobagyi, G.N., Stanbridge, E.J., and Lee, E.Y-H.P. 2008. Cancer stem cells contribute to cisplatin resistance in Brca1/p53- mediated mouse mammary tumors. Cancer Res. 68: 3243-3250.
Lung, H.L., Lo, P.H.Y., Xie, D., Apte, S.S., Cheung, A.K.L., Cheng, Y., Law, E.W.L., Chua, D., Zeng, Y.X., Tsao, S.W., Stanbridge, E.J., and Lung, M.L. 2008. Characterization of a novel epigenetically-silenced gene, ADAMTS9, and its association with lymph node metastases in nasopharyngeal carcinoma. Int. J. Cancer 123: 401-408.
Kaluz, S., Kaluzova, M., and Stanbridge, E.J. 2008. Rational design of minimal hypoxia-inducible enhancers. Biochem. Biophys. Res. Comm. 370: 613-618.