Summer Research Spotlight: Emily Harrison
By Emily Harrison, Special to The Gettysburgian
During my sophomore year at Gettysburg I fell in love with the field of organic chemistry. And this love motivated me to spend last winter break applying to thirteen universities’ summer research programs that would allow me to study a subject most people do their best to avoid. I was accepted to an excellent program that allowed me to do exactly that—Summer Research Opportunities at Harvard (SROH). Through SROH, I conducted research in Dr. Matthew Shair’s lab in the Department of Chemistry & Chemical Biology at Harvard University for ten weeks this past summer. More specifically, I worked under the guidance of a fifth year Ph.D. student named Rocco, who trained me and taught me more than I ever thought I could learn in just one summer.
The broad goal of Rocco’s research project is to prevent increased expression of an important metabolic regulating enzyme called nicotinamide N-methyltransferase (NNMT). The activity of NNMT is closely related to the processes of energy expenditure and DNA methylation, but overexpression of this enzyme may promote the onset or worsening of diabetes, diet-induced obesity, and several types of cancer. Thus, Rocco has designed a library of small organic molecules that have two structural motifs, each mimicking the structure of one of NNMT’s two natural substrates, connected by a covalent linker. This concept is known as bisubstrate inhibition—one molecule is designed to selectively block both binding sites on an enzyme so that the enzyme can no longer function properly. The inhibitors Rocco has designed and synthesized over the past few years have the potential to be used as novel therapeutics for cancer and obesity.
My job this summer was to assist with the optimization of our synthetic strategies towards a few of the NNMT inhibitors. I spent most of my time working on the twelve-step synthesis of NS-1, which is the inhibitor that has exhibited the most selectivity and potency against NNMT thus far. I began each reaction in the synthetic scheme on a very small scale, around 25-50 milligrams, and tried out slightly different reaction conditions until I found an efficient strategy that afforded a high chemical yield. I then scaled up the reactions in increments to eventually reach a one or two gram scale. Shorter and more effective synthetic strategies are imperative in the lab and in the pharmaceutical industry, in order to efficiently build up stocks of each inhibitor for biological testing and to then produce them in quantities sufficient for commercial marketing.
This research was so fascinating to me because I was not only able to do organic chemistry for 10+ hours each day, but I was also able to employ my work in a much greater context. Chemistry intrigues me day in and day out, but it becomes most important when it can be applied to solve problems that would otherwise be unapproachable without a fundamental understanding of science. This summer confirmed my plans to hopefully attend graduate school after my four years at Gettysburg are over and devote my career to exploring organic chemistry and its important applications in the real world. All the organic reactions and mechanisms may seem tedious in the classroom, but if they can cure cancer then they’re absolutely worth it.