Q: What do you do in your work?
A: We basically, as a group, are very much interested in what regulates growth signals in a cell. We look at how cells grow under normal situations when they are healthy, and then what goes wrong during diseases. A lot of the signals that directly feed into how cells grow, multiply and survive are regulated by this group of memory receptors, which are called receptor tyrosine kinases. These are like cell surface antennas that bind to molecules on the outside. Something happens to them: they change their protein structure conformation, get activated and then a lot of different things get activated in the cell’s pathways, and those pathways lead to the core functions of the cell, like the decision of whether to survive, whether to migrate, or whether to die.
So my group goes very basic into understanding this question and we actually look at the molecular machines, the proteins themselves, and how they change in response to the binding of those ligands. The very interesting property is, when they bind these ligands, they start to grope and form this higher order, which we call supramolecular complexes. When a lot of them come together they activate each other, then they recruit proteins from inside of a cell. No one understands what these complexes really look like because they are very difficult to study. So we are trying to use structural biology and high resolution fluorescent imaging to kind of get a molecular snapshot, like a picture of that to interpret what that means for the regulation of growth signals.
Q: What’s your favorite part about being a scientist?
A: I think that the favorite part for me is the fact that every day at work is different. I really actually have no idea how to predict what will happen because things happen in the lab all the time and new things come in. Also, I never really feel forced to work; I actually usually feel frustrated if I don’t have enough time to be here. I like that and I think it’s a passion, and it’s very much rewarded by finding out something that no one has ever seen before. It’s a little bit like an expedition...like an exploration. I like it the most.
Q: What have you created or discovered that you are most proud of or excited about?
A: We have made quite an amazing progress on trying to purify the stable receptors that I just described. It’s very difficult to get them in one piece because of many different biophysical problems that we encounter while getting these guys to get out of the cell and behave so that we can take them out and look at them. So this is where we are right now. We have pretty good mechanisms in place to do it. I am also very proud of the collaborations that we have established here at UCSF that helped us in a lot of ways. Altogether we are at this point where we can combine a lot of expertise that we have, to accomplish something that hasn't been done before. So I’m hoping that this big thing is still ahead of us, but I am very proud of all these small steps that we have taken.
Q: At the end of the day, why does your work matter?
A: I think that we are very much driven by trying to find new ways to treat diseases. I think that’s important, just for that reason. Most of the time, the best drugs that people have found are best because we understand how they work and we can then optimize them when the human diseases become resistant to these drugs.
But frankly, I think that the most important thing is that people actually want to know how things work, and we discover these basic principles behind how things behave. I think that’s important… it’s why people even do science since the beginning of the world. You discover why you are here and how you function. It just has to continue because we still have more to learn.
At UCSF I find that people are extra passionate about what they’re doing. Being in a group of people who are passionate means that when you fail and are in a dark corner, you can share it with somebody and they say, “Well, hey, why don’t you try this? I heard such and such got this to work with that.” So I think this level of communication helps to pass this information faster so that you have access to more knowledge. By yourself it’s hard to know everything.
Q: Outside of work, what do you do to relax?
A: So I have two young children, ages two and five. So I basically spend time with them. It’s a relaxation on a different level. I love to just go to a park with them, run around, play some soccer...so a lot of physical exercise with the kids, which is the best relaxation for me. They are happy, I’m happy and we’re all tired, so everybody goes to sleep fast with no complaints. I always try to make sure that on the weekends, at least, I have a couple of hours to relax. But I don’t have a particularly cool hobby because of lack of time. The job can overtake your life a little bit, so it’s important to have balance, especially if you have other obligations. But I think it’s a good thing because you look forward to Mondays.
Q: What is something that makes you uncomfortable?
A: It’s a very good and deep question. I try to find myself pretty much in every situation. But maybe if I had to go to DC and talk about scientific policy, that would make me very uncomfortable. I would really have to prepare for it and think about it to do it right. So I guess talking to politicians about science.
Likewise, talking to people who are not scientists about science. I always have to make sure I think about how I do that in a proper way. You want them to benefit from the conversation and you don’t want to be boring, but sometimes we’re so into the details. But I wouldn’t call that being uncomfortable; it just takes more time to prepare the thought. It’s not my forte.
Q: In 50- 100 years, what do you want to be remembered for?
A: Definitely, I would love to figure out how receptor tyrosine kinases signal. I would love to solve the structures of the full-length proteins and understand how it works. But I hope very much that this research actually helps us get somewhere in terms of improving how we treat diseases in which their signaling is deregulated. I would also like to be remembered for being a great colleague and an inspiring mentor, because I have such people in my mind and even if those people are maybe not the most successful scientists, I think about them the most highly because they inspire others to discover other things. I would love if people thought that about me.