This proposal describes a 5 year training program for the development of academic career in Surgery. The principal investigator has completed a combined M.D./Ph.D. program at the Washington University and an ACGME accredited residency training program in Otolaryngology-Head and Neck Surgery at the University of California San Diego (UCSD). She has also completed a postdoctoral fellowship in Skull Base Surgery at UCSD and now, will expand her combined training in clinical medicine and scientific research through an unique integration of interdepartmental expertise and resources. Dr. Roger Tsien will mentor the principal investigator's scientific development. Dr. Tsien is a recognized leader in the field of cell biology and neurobiology and is world renowned for developing colorful fluorescent dyes for monitoring intracellular processes. He has been a Howard Hughes Investigator since 1989, is a Professor in the Dept of Pharmacology at UCSD and has trained numerous postdoctoral fellows and graduate students. To enhance the training, the program will also have an advisory committee of physician scientists who are leaders in their fields and who will provide scientific and career advice. Research will focus on the development of an animal model for molecular fluorescence guided surgery.
The specific aims i nclude 1) develop an imaging system for fluorescence guided surgery in small animals, 2) develop animal models for fluorescence-guided surgery, with quantitative objective criteria for accuracy of excision 3) develop animal models for whole body imaging coupled with fluorescence image guided surgery Despite recent technological advances in the noninvasive diagnosis of cancers including CT, MRI and PET imaging, the main treatment modality for solid malignant tumors is surgical excision. However, surgical excision of tumors remains dependent on the individual surgeon's ability to differentiate tumor from normal tissue using non-quantifiable criteria such as tumor location, texture, color, relationship to surrounding structures etc. The relevance of this project is to provide the operating surgeon with a sensitive molecular marker visualizable in real time to differentiate tumors from non-tumor tissue intraoperatively, thereby guiding surgical excision.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
Special Emphasis Panel (ZEB1-OSR-B (O1))
Program Officer
Erim, Zeynep
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Schools of Medicine
La Jolla
United States
Zip Code
Metildi, Cristina A; Felsen, Csilla N; Savariar, Elamprakash N et al. (2015) Ratiometric activatable cell-penetrating peptides label pancreatic cancer, enabling fluorescence-guided surgery, which reduces metastases and recurrence in orthotopic mouse models. Ann Surg Oncol 22:2082-7
Levin, Rachel A; Felsen, Csilla N; Yang, Jin et al. (2014) An optimized triple modality reporter for quantitative in vivo tumor imaging and therapy evaluation. PLoS One 9:e97415
Savariar, Elamprakash N; Felsen, Csilla N; Nashi, Nadia et al. (2013) Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cell-penetrating peptides. Cancer Res 73:855-64
Olson, Emilia S; Whitney, Michael A; Friedman, Beth et al. (2012) In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity. Integr Biol (Camb) 4:595-605
Wu, Amy P; Whitney, Michael A; Crisp, Jessica L et al. (2011) Improved facial nerve identification with novel fluorescently labeled probe. Laryngoscope 121:805-10
Baik, Fred M; Nguyen, Linda; Doherty, Joni K et al. (2011) Comparative case series of exostoses and osteomas of the internal auditory canal. Ann Otol Rhinol Laryngol 120:255-60
Whitney, Michael A; Crisp, Jessica L; Nguyen, Linda T et al. (2011) Fluorescent peptides highlight peripheral nerves during surgery in mice. Nat Biotechnol 29:352-6
Nguyen, Linda T; Harris, Jeffrey P; Nguyen, Quyen T (2010) Erosive external otitis: a novel distinct clinical entity of the external auditory canal in nonimmunosuppressed individuals. Otol Neurotol 31:1409-11
Nguyen, Quyen T; Olson, Emilia S; Aguilera, Todd A et al. (2010) Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival. Proc Natl Acad Sci U S A 107:4317-22
Olson, Emilia S; Aguilera, Todd A; Jiang, Tao et al. (2009) In vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. Integr Biol (Camb) 1:382-93