Q: In a couple of sentences, tell me about what you do in your work.
We study how neurotransmitters and neuromodulators work on their target neurons and we try to understand the basic mechanisms by which drugs act for receptors and by which receptors modulate physiology normally.
Q: What’s your favorite part about being a scientist?
Discovery is a rush and working with really smart people as they discover things is even more of a rush. We have some fabulous students and postdocs here at UCSF. It’s probably the best students and postdocs in the world. We are very fortunate to have such great folks to work with, and that’s a double rush when they succeed.
Q: What have you created or discovered that you are most proud of or excited about?
Well, one of the things that got some press with respect to Weill because it was partly supported by the Weill Institute (very important support) was a recent discovery having to do with the location of receptor activation in cells. With opioid receptors, which are the targets of drugs like morphine, fentanyl, and oxycodone, the belief in the field had been for many years that these receptors are activated on the cell surface where they have been thought to exclusively function. This is true, they are activated on the cell surface and they do mediate important functions there, but what Miriam Stoeber, a very talented postdoctoral fellow in the lab, was able to discover was they can also be activated inside of cells and there is a particular location inside of cells that drugs can activate these receptors at. The natural ligands for these receptors that are normally what (in physiology) are controlling behavior, cannot access the receptors at that location.
That, I think, is quite exciting and has a lot of implications but also is telling us that we really have a lot more work to do to figure out what the significance of these different locations of activation is. That’s one of the things that we’re really excited about right now.
And I should mention along with that line another thing that’s really fun at UCSF is collaboration because that work really benefited from collaboration with Aashish Manglik, who is a professor in Pharmaceutical Chemistry here. The tool that Miriam developed to detect the location of receptor activation was actually developed in collaboration with his lab.
Q: At the end of the day, why does your work matter?
Ultimately, my lab is a basic science lab. What we are hoping to do is understand the basic sort of rules of biology. We think that if you don’t have a clear understanding of the basic rules of how things work, therapeutics is built on a really flimsy foundation. So I would say that ultimately that’s sort of our identity as a laboratory. We really try to get the basic, fundamental principles and mechanisms right to provide a solid foundation for therapeutics.
In the process of doing that we also occasionally find potential targets for therapies and I’m delighted that there have been a few successes indirectly related to that. Our main goal in our lab is to really try to understand the principles and to get those details right as a foundation.
Q: Outside of work, what do you do to relax?
Lots of fun things. My wife and I do a lot of gardening. I’m a bit into music, although not very good, which is why I haven’t quit my day job, and I like bicycling and kayaking.
Q: What situation do you think you’d feel the most out-of-place in? What is something that makes you uncomfortable?
Politics. I don’t get it. Common sense seems not to matter and that I find very hard to understand. As I scientist I somehow have this deep faith in reason and logic and the importance of truth, and that’s very hard to understand when you’re dealing with a world that doesn’t seem to be grounded in any of those principles.
Q: In 50- 100 years, what do you want to be remembered for?
Having a really really big, contaminated lab that I’ve left a big mess in so that people will say “Oh, that was THAT guy.”
Journalism credit: Alexa Roucourt