Candidate: The candidate has been involved in clinically relevant basic science research during the post-doctoral studies. This training and the candidate's understanding of confounding clinico-pathologic issues have contributed to her commitment to pursue translational research in oral cancer. The immediate goal is internationally renowned clinician- scientists. The long-term goal is to become an independent translational scientist capable of bridging the gap between the laboratory bench and patient care. Environment: The University of Michigan is a nurturing environment for the clinician-scientist. The Cancer Center is internationally reputed for its pioneering work in clinical and biomedical research. The developments in basic science knowledge are translated into improvements in patient care. Research Career Development Plant: The plan encompasses the 5 year award period and includes supervised basic science and translational research rotations, Head and Neck Cancer Symposia, weekly signaling, research responsibility and ethics. Research Project: The overall objective of this proposal is to enhance the understanding of the molecular choices of oral cancer. Rap1, a ras-like protein, will be evaluated as a predictive biomarker for malignant transformation of precancerous human oral epithelial lesions. Additionally, a rap1B, a rap1 isoform, will be assessed as a candidate protein for prognosis prediction, when used as a biomarker for metastatic potential of squamous cell carcinoma (SCC). This would allow the identification of lesions that should be treated more aggressively. The third segment involves the design of a protocol to investigate the use of rap1A in gene therapy to treat residual epithelial dysplasia or squamous cell carcinoma lesions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DE000452-05
Application #
6702599
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Hardwick, Kevin S
Project Start
2000-01-01
Project End
2005-12-31
Budget Start
2004-01-01
Budget End
2005-12-31
Support Year
5
Fiscal Year
2004
Total Cost
$130,680
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Dentistry
Type
Schools of Dentistry
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Mitra, Raj S; Goto, Mitsuo; Lee, Julia S et al. (2008) Rap1GAP promotes invasion via induction of matrix metalloproteinase 9 secretion, which is associated with poor survival in low N-stage squamous cell carcinoma. Cancer Res 68:3959-69
Zhang, Zhaocheng; Mitra, Raj S; Henson, Bradley S et al. (2006) Rap1GAP inhibits tumor growth in oropharyngeal squamous cell carcinoma. Am J Pathol 168:585-96
Wolter, Keith G; Wang, Steven J; Henson, Bradley S et al. (2006) (-)-gossypol inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma in vivo. Neoplasia 8:163-72
Henson, Bradley S; Neubig, Richard R; Jang, Ilwhan et al. (2005) Galanin receptor 1 has anti-proliferative effects in oral squamous cell carcinoma. J Biol Chem 280:22564-71
D'Silva, N J; Mitra, R S; Zhang, Z et al. (2003) Rap1, a small GTP-binding protein is upregulated during arrest of proliferation in human keratinocytes. J Cell Physiol 196:532-40
Mitra, Raj S; Zhang, Zhaocheng; Henson, Bradley S et al. (2003) Rap1A and rap1B ras-family proteins are prominently expressed in the nucleus of squamous carcinomas: nuclear translocation of GTP-bound active form. Oncogene 22:6243-56
Chen, Hen-Li; McCauley, Laurie K; D'Silva, Nisha J (2002) cAMP binding protein assay for widespread use in cell signaling studies. Biotechniques 33:66-8, 70, 72