I’ve been a member of Dr. Isaac Carrico’s organic chemistry lab for over 3 years, working primarily on viral engineering and bioorthogonal reactions.
The project I focused throughout my undergraduate career was the chemoselective modification of adenoviruses with radioisotopes through the development of a viral photocages. This project was completed in collaboration with Kelly Henry, a post-doc in Dr. Jason Lewis’s Research Lab at Sloan Kettering, to create viral therapies that can be targeted for treatment while simultaneously allowing us to visualize their biodistribution in vivo. Throughout this process I improved my synthetic chemistry skills, learned purification skills such as HPLC and column chromatography, performed and analyzed in vitro experiments, and learned how to effectively collaborate with others.
As I transitioned from an undergraduate to a graduate researcher, I decided that I no longer wanted to focus solely on adenovirus engineering, I now want to expand into our other lab focus: bioorthoganal reactions. A bioorthorganal reaction is one that doesn’t interfere with any chemical reactions that occur naturally in a cell or organism. Similar to my previous work with adenoviruses, this can be used for tracking drugs and other small molecules to learn about biodistribution and now it can be done without altering the microenvironment or inducing cellular toxicity. Previously, when Dr. Lisa Shah was completing her PhD in Dr. Carrico’s lab, she was able to incorporate light sensitivity while improving upon the Staudinger-Bertozzi ligation. By using light as the external stimulus, she was able to enable spatiotemporal labeling of metabolically induced azides both in vitro and in zebrafish.
For my graduate research project, I plan to expand upon the work that Dr. Shah did to bring this incredibly useful reaction one step closer to actually being used in humans for imaging or tracking small molecules. In order to do so, I plan to replace the FLAG peptide with a variety of other epitope tags and immunofluorescents. FLAG was used in the original molecule as a proof of concept because it is one of the most widely used and well characterized epitope tags but it cannot be translated to in vivo human applications. In order to find another method for florescent detection with a Staudinger-Bertozzi product will take multiple tests for efficacy as well for safety and tolerability. Along with testing and analysis of various FLAG replacements, I will also be testing how we can use different wavelengths of light, preferable infrared or near infrared, to initiate the light sensitive Staudinger-Bertozzi ligation. Using lower frequency wavelengths will allow us to use deeper penetrating light sources that can be used in humans for the identification of tumors, to track biodistribution, or a variety of other applications. The ability to photoactivate a Staudinger-Bertozzi ligation as a result of my research, will give us the ability to analyze biological and pharmacological processes biorthogonally and in a more controlled manner than ever before.