The candidate's goal is to advance her academic career by becoming a translational scientist through additional basic research and didactic training supported by a K08 Clinician-Scientist Development Award. The candidate is an Assistant Professor in the Clinician-Research-Teacher tenure-track at the University of Rochester School of Medicine, Department of Emergency Medicine. The candidate graduated from medical school in 1998 receiving an MD with Distinctions in Research, and since has successfully combined postdoctoral studies in basic research (80% effort) with clinical practice (20% effort). To reach her professional goal, the candidate proposes here a career development plan that will enable her to obtain additional training through coursework specifically designed to educate translational scientists as part of the curriculum available by the recently awarded CTSA NIH grant to our Institution. Moreover, the candidate will continue to pursue her successful research plan in skin cancer biology, coupled with advanced level courses in basic sciences. To this end, the candidate has discovered that in UV-induced skin cancers, the facilitative (pro-oncogenic) down-regulation of E-cadherin, an adhesion molecule mediating cell-cell contacts between keratinocytes, is a post-translational event consisting first of extracellular E-cadherin domain cleavage (primarily by MMPs), followed by endocytosis and proteolytic/lysosomal-proteasomal degradation. Moreover, the candidate has discovered that this process is regulated by activation of the EP2 receptor by PGE2 released locally after UV radiation injury. As part of this K08 award, the candidate will continue her studies on this topic, which ultimately will lead to the identification of new targets for pharmacological intervention against UV-induced skin cancers. Completion of the proposed plan will enable the candidate to receive a Master's in Translational Science degree as part of her K08 award. Due to the diverse nature of the proposed training, the candidate has recruited a mentorial committee that provides the necessary mentorship, expertise and support. In conclusion, this K08 award will prepare the candidate for a career in basic/translational science, whereby she will be able to (1) identify novel scientific discoveries and their potential clinical usefulness in animal models (preclinical studies) in the laboratory, (2) evaluate such discoveries through clinical trials and (3) bring their use to clinical practice (bench-to-bedside-to-curb).
|Brouxhon, S M; Kyrkanides, S; Teng, X et al. (2014) Soluble E-cadherin: a critical oncogene modulating receptor tyrosine kinases, MAPK and PI3K/Akt/mTOR signaling. Oncogene 33:225-35|
|Brouxhon, Sabine M; Kyrkanides, Stephanos; Raja, Veena et al. (2014) Ectodomain-specific E-cadherin antibody suppresses skin SCC growth and reduces tumor grade: a multitargeted therapy modulating RTKs and the PTEN-p53-MDM2 axis. Mol Cancer Ther 13:1791-802|