Oftentimes, big events are provoked by small triggers; like the errant spark that starts a wildfire, tiny chemical changes to receptors in the human brain can trigger big changes in the patient. PhD student Ryan McGlynn is a pharmacologist and researcher in Northeastern’s Department of Pharmaceutical Science and has devoted himself to mapping the way chemical compounds applied to serotonin receptors can alter behavior. “First we’re asking the question, what’s happening at the receptor level? Once we know that, we’ll move on to what’s happening at the neuron level and look at MRIs and the like to see what’s getting turned on and off,” he explains, “then we can hopefully tie this to actual changes in behavior and health.”

After graduating from the University of Pittsburgh with a degree in chemistry and a keen interest in research, McGlynn worked with a small chemical startup developing custom molecules for several large clients, including General Electric, the Department of Defense and Amgen. While working with Amgen, his conversations with his counterparts there introduced him to pharmaceutical science and the field of drug development, which in turn led him to Northeastern and his current role as a researcher in the lab of Professor Raymond Booth in the Center for Drug Discovery, where he has worked for the last 3 years.

McGlynn is now working on developing what are essentially custom-tailored medications. He explains, “There are 17 serotonin receptors, 16 of them are called ‘G protein-coupled receptors’ which are highly targeted by drugs – something like 40% of drugs target those type of receptors. What I’m working on now is, we’re teasing out what makes a compound bind to a specific receptor, because if you can isolate that one, you can use it for the therapeutic properties without having any bad side effects.”

“I’ve picked two receptors to focus on,” he continues, “What’s cool about the two I’ve picked, the 1A and 7 serotonin receptors, is that they’re very similar, but have inverse functions. 1A is inhibitory and 7 is stimulatory, but they’re 70% similar. So it’s a question of teasing out which amino acids are responsible for one being stimulatory and one being inhibitory, and what confirmations of the compound and the receptor together cause the stimulation and inhibition, because it’s all in the nervous system. You’re turning neurons on and off depending on which receptor you’re targeting.”

This research has produced some intriguing results; “We’ve found that 7 is doing a lot with memory,” McGlynn explains, “and we have a 1A molecule that has slowed opioid self-administration, so we think it’s tied to reward pathways. So you might want to shut down that reward pathway for opioid abusers so they don’t have that need or craving as much, and hopefully prevent them from seeking them out.”

This work has directly fed into his dissertation, which he is in the process of developing now. “My research for the next three year is going to have several layers. We have the advantage of a large library of compounds, so right now we’re figuring out those essential building blocks and figuring out which compounds are biased towards which signaling pathways within 1A and 7. We have compounds that bind to both of them, so we’re finding out what parts of the receptors they’re binding to, and what we can exploit about the different parts of these two receptors to further refine molecules that will only selectively target one receptor, a sort of designer molecule.”

While much work remains to be done, McGlynn is optimistic about the potential of this research. “I think this could have a really visible, long-term effect. If this can do everything that we think it can do, and we can get a compound exactly right so it has the right effect on behavior, it could be a pretty big game-changer. It wouldn’t solve everything, but it would push the knowledge forward, which is what everyone else is doing as well.”

McGlynn’s excitement is tangible as he continues, “If we can capture the small changes at the receptor level and then connect how those neuron responses affect behavior, we can then hopefully use it as a blueprint for other things. Hopefully other scientists will take our work and apply it to their own research. This just addresses two receptors, after all – there are 15 other ones!”

This opportunity to contribute so impactfully to scientific discourse is obviously tempting, but McGlynn sees his work as part of a far greater effort. “More than anything I want to provide other scientists with better tools and diagnostics so they can spend less time and money in their research.”

While he doesn’t have concrete plans for after completing his PhD, the pharmaceutical industry’s allure is undeniable. “I’m not really sure where I want to end up after,” says McGlynn, “I’m very intrigued by the field of medical affairs, particularly the role of medical liaison…I’m also really interested in medical writing.”

“I don’t hate the bench top,” he’s quick to add with a laugh, “I’m a people person, and I just really like to talk to people about science. I want to be at the center of the Venn diagram, able to be an intermediary and translator between the deep scientific part and the more lay side of the field.”