Kamara Holmes, COL ’25, Smyrna, GA
This summer, I was fortunate to continue the molecular biology phase of my independent research project under the guidance of Dr. Elizabeth Heller in the Department of Systems Pharmacology and Translational Therapeutics here at Penn.
Understanding the epigenetic mechanisms underlying addiction and other neuropsychiatric disorders is one of the primary objectives of the Heller Lab. A previous paper published by the lab concluded that activation of a druggable nuclear receptor Nr4a1 reduced cocaine-seeking behavior (i.e. “cravings”) in mice that were primed/“addicted” to the drug through its downstream activation of Cartpt (cocaine- and amphetamine protein transcript). Given that cocaine use disorder (CUD) affects nearly 1.2 million Americans per year yet there are currently no FDA-approved therapeutic treatments for it, this was a very significant finding.
Cytosporone B (Csn-B) is a compound that can be naturally found in various fungal species and is well-characterized as an activator of Nr4a1. However, Csn-B has been shown to be rapidly metabolized, resulting in poor bloodstream bioavailability and making it a nonviable therapeutic alone.
So, in response to this, I spent my Spring semester working under Dr. Dirk Trauner (Department of Chemistry, UPENN), where I synthesized and purified Csn-B and three derivatives. Then, this summer, I brushed up on my cell culture techniques and tested the effects of my compounds in both mouse and human cell lines. I performed numerous experiments to assess two things: compound effect on cell viability (i.e. how toxic are these compounds) and their effect on Nr4a1 activation (i.e. do these compounds have the desired biological effect).
The progress that I have made this summer has been invaluable to my success here at Penn and beyond. This project is the centerpiece of my submatriculation into a Master of Chemical Sciences degree, after which I plan to obtain a Ph.D. in Medicinal Chemistry. Furthermore, this immersive hands-on experience has strengthened my skills in experimental design, visual and written communication, time management, molecular biology techniques such as Western blotting and cell culture maintenance, and statistical analysis.
In conclusion, I would like to extend a huge thank you to Penn Career Services, as this story would not have been nearly as successful without their generous funding. I want to thank Dr. Heller for her nurturing feedback and her endless belief in me, as she has helped me blossom as both a scientist and a person. She took a chance on me over a year ago when she initially offered me a position in her lab and words cannot express how profoundly grateful I am every single day. Absolutely none of this would have been possible without her. I would also like to express my gratitude to Zoe Sessions (Pharmacology Ph.D. candidate, Trauner Lab) and Dr. Julia Winter (Postdoctoral researcher, Heller Lab) for their guidance throughout the course of this project. I will spend the rest of my time here at Penn continuing my work and honing my skills as a budding scientific researcher.
This is part of a series of posts by recipients of the 2024 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here
