I grew up in an Armenian community in Lebanon and I was about seven years old when the Civil War started. It was tough times. We almost never went out at night. We were always worried about bombs falling. Even though Lebanon is a very special place and I have many fond memories of being in the beautiful countryside, it’s juxtaposed with terrible memories of war. For example, when I was walking back from a party from East Beirut to West Beirut at age 18, militants thought I was suspicious, so they held me for a day and asked me all kinds of questions at gunpoint. Eventually they realized I was harmless, but it was very terrifying. That experience led me to leave Lebanon. I have not been back since.I came to Los Angeles shortly after, where I would eventually find my way into science. It was, at the time, a big shock. I thought I knew how to speak English and didn’t realize how dialect is difficult to understand. I didn’t have the financial means to go to college immediately. I held multiple jobs. I grew up really fast. I think if you live by yourself in a new country, you go from being a kid to an adult within a month or two. I also quickly realized how different it was here, and how privileged it was to have electricity all day long and other things that we take for granted. I think I’ve tried not to take things for granted based on these experiences and that’s served me very well in life and later in science.
I came to Los Angeles shortly after, where I would eventually find my way into science. It was, at the time, a big shock. I thought I knew how to speak English and didn’t realize how dialect is difficult to understand. I didn’t have the financial means to go to college immediately. I held multiple jobs. I grew up really fast. I think if you live by yourself in a new country, you go from being a kid to an adult within a month or two. I also quickly realized how different it was here, and how privileged it was to have electricity all day long and other things that we take for granted. I think I’ve tried not to take things for granted based on these experiences and that’s served me very well in life and later in science.
When I came to the U.S., I didn’t even realize that science as a career was a possibility. My idea was to go to medical school. As a premed at UCLA, the only reason I worked in a laboratory was to get a letter of recommendation for medical school. But once I started working in the lab, I absolutely fell in love with doing science, the international group of interesting people and especially the culture of discovering new things and asking questions that no one’s asked before. I immediately realized this is my calling and I should let go of my dreams to go to medical school and do this instead. And I’m very glad I did it. I find it very interesting because it’s such a random way of finding your calling.
My mom had a master’s degree in biology and she taught science. Like many parents, including immigrant parents, they were really keen on me going to medical school, so they were a bit disappointed at the time when I decided to go into science. I have an 18-year-old son now, and I talk to him a lot about exploring options to find his calling because it’s a wonderful thing to do something that you really love and would probably do it even if no one paid you. I would say to fellow parents, even when it’s hard: let kids explore. What you think might not be practical, might end up being very practical and very good for them.
My lab discovered cellular receptors called PIEZOs. While most of your cells in your bodies communicate through chemicals, PIEZOS do something very special: they sense mechanical force or physical force. It was known that there were molecules and proteins that sense mechanical force, but the identity of the receptors was not known. What’s exciting about PIEZOs is that they play very important roles in almost every process in our body that depends on pressure sensing. This includes touch, proprioception and pain, as well as sensing pressure in internal organs, such as blood pressure, stomach stretch, bladder stretch, et cetera.
There was certainly a feeling of “eureka,” but the discovery actually happened in phases. It started with laborious work by my postdoctoral fellow, Bertrand Coste. Before that eureka moment, it took him almost two years to get to that point, which was frustrating and difficult at times, so persistence was important. Bertrand is a very understated guy, so when he came to my office and said that he found it, he was so calm that it didn’t even register for me. But we looked at the data and we got excited. We had an idea that this could be important, but honestly it ended up being much more interesting than we even imagined. It took many other postdoctoral fellows and students four or five years of seeing the consequences, so our excitement at the profound importance of PIEZOs grew year after year.
Proprioception is one of the most important senses that most people don’t know about because you’re not conscious if it. It’s essentially the feeling of the position of your limbs in space. It’s required for walking and tasks we take for granted. For example, if I close my eyes and raise my hand, I know exactly where my fingertips are. PIEZOs, being pressure sensors, are actually doing all the important sensing required for proprioception. Without them, you don’t sense your muscles stretch. And if you don’t sense the muscle stretch, you don’t have this feeling of where your limbs are in space.
Interoception, on the other hand, is sensing of internal organs, which is more complicated and less understood, than say, the sense of touch from your skin. For instance, you have neurons dependent on PIEZOs, which monitor every beat of your heart and also the blood pressure inside your aorta. As pressure increases in the aorta, PIEZOs sense it and reduces blood pressure to a normal level. It’s very important for survival, but you’re not aware of it at all. Interoception is also responsible for internal sensations you are aware of, like a full bladder.
What’s really exciting about the field of interoception is that we are finally starting to understand how these signals are processed, how decisions are made, and how these affect your behavior or turn pathological in old age. Many neuroscience labs at Scripps Research are studying these questions tied to interoception from different angles.
We think that future research on mechanosensation and PIEZO channels could help find novel medicines for treating pain, hypertension, urinary incontinence, diabetes, and many other conditions. As we know, hypertension is a major medical problem and some types are not very easily resolved. Understanding more about the molecules that sense hypertension could give us molecular and cellular targets for treatment. Satiety is another form of interoception, where the mechanical stretching of the stomach signals fullness and has consequences for obesity and diabetes, but we know very little about this kind of signaling. In another example, in red blood cells too much signaling of PIEZOs causes red blood cell dehydration, which might cause anemia. But we have found that on the positive side, it might be protective against malaria.
What is exciting about this discovery and basic science in general is that applications can come from directions you never anticipated. This is the greatest argument to justify why we should invest in basic research. We identified PIEZOs as important for touch and pain, and the most obvious implication for this is potentially helping find new cures to pain and other diseases, but now we see there is much more in human health that PIEZOs could impact. Another interesting application of PIEZOs is tied to haptics and artificial sensors. By learning how natural mechanosensation and touch sensation work, we can better help in designing new sensors for people who have lost limbs, for example. So, learning more about PIEZOs can have impact in very interesting, but relatively unrelated, fields of research.
I think all of us were really in shock. But my family is very down to earth, and since then, they have formed a committee to make sure that my head doesn’t get too big, which I really appreciate. And my wife made a Nobel Diva card, which I get to use only once a week for a year for things like getting out of doing the dishes.
What’s hard to anticipate is how excited people get and how wonderful it is to hear from friends and colleagues and places you’ve been associated with. I knew the Nobel Prize was important, but I really didn’t realize the impact it has around the world. I received about 50 letters from elementary school kids saying how proud they are of me and how now they want to be scientists. I want to use this recognition to do some good, including inspiring young kids to become scientists.
I’m Armenian, that was my native tongue, but I also was born in Beirut, Lebanon. Seeing the excitement of the Lebanese and Armenian community has really reconnected me to those cultures. This happens to be the first Nobel laureate for anyone of Armenian origin as well as anyone from Lebanon. These countries have had a rough couple of years, both economically and in terms of war, so they celebrated this news and I really cherish that.
Many people think that once you win the Nobel Prize, you will hang up the lab coat and do just administrative stuff or other things. But I love being in the lab. I love asking these basic questions to understand how our body works, and I don’t want any of that to change. I’m committed to keep working in the laboratory with these incredible young scientists and make new discoveries.
I think our trajectory in studying pressure sensation has taken on two phases. The first phase was to identify PIEZOs and show their importance. Phase two, which I’m even more excited about, is finding more on the novel biological processes and diseases that depend on mechanosensation—this includes important roles in red blood cell regulation, and many other different roles of cells and tissues that, again, we haven’t really thought about in the past to depend on pressure sensing. But clearly what we missed is that almost every cell responds to mechanical forces, and we have known virtually nothing about this. PIEZOs really opened the door to so many more areas of study and novel applications.
Science is an interesting career because there’s lots of busy work but also a lot of thinking involved. I find exercises like walking and running great times to think of new ideas. I’m obsessed with science, and I often think about it all the time: when I wake up, in the middle of a run, and so on. I love the great outdoors. I used to go running with colleagues at Scripps Research two to three times a week for years and years. Unfortunately, I have a bad knee now and I can’t run as much, but I still do lots of outdoor activities like walking and biking. I go swimming and backpacking with fellow faculty.
I am also a really big fan of the arts. I think arts and sciences have a lot of in common in creativity and I enjoy both. I especially love music of all kinds—eighties rock, classical, opera, jazz.
My biggest advice to young scientists is to be fearless. I think that’s so important because many times we think of an interesting question, but we worry that it might be risky, or that there are competitors, or that you might simply fail. But nevertheless, it’s worthwhile taking the risks to try to do something important and meaningful.
If I think back on 20 years ago when we started this line of research, I realized what a big risk I took working on something that was very difficult to do; that many other labs were trying to do; and that had a very high chance of failure. But that challenge is why we love science, and I’m glad we took that route.
Scripps Research is, as I like to say, incredibly good for basic research, but is also one of the best academic places where translational research is being done. And the intersection of these two makes Scripps Research really unique. Also, it’s a collaborative place where there’s not too much bureaucracy. The institute brings people together from different areas of chemistry and biology that would normally not collaborate and work together. For example, when I joined Scripps, I was more of a developmental neuroscientist, but being in this environment made me realize the importance of translational work. Although my lab’s main question is to understand basic fundamental questions in biology, we’re now also always thinking, “How could this be translated to help contribute to cures for human disease?” And this juxtaposition makes Scripps Research a very special place that’s played an important role in my work.