“Pain is very mysterious and puzzling in how it works…What are the changes that permit or allow these long-lasting pain states?”



An Interview with Ishmail Abdus-Saboor, PhD
Assistant Professor of Biology, University of Pennsylvania

By: Michelle Johnson

Can you briefly describe the main hypothesis or research question on your mind right now?
We [the Abdus-Saboor Lab] are interested in how our nervous systems can encode unique sensory stimuli. If I blindfolded you right now, you held your arm out, and I gave you a hot stimulus or a cold stimulus or a poke with a needle or a soft caress with a feather, you would tell me immediately how it felt, even though you couldn’t see it and had no expectation of what was coming. The reason you can do that so well is because our nervous system is tuned to be able to respond to different stimuli within milliseconds to tell us what it is we’re experiencing so that we know how to respond properly. How does any of that work? We’re interested in how we perceive sensory stimuli, mainly in our skin, in both normal scenarios and disease states.

What excites you most about your work?
I’ve always been the type of person who’s motivated by important questions, really challenging puzzling questions; I like a challenge. Some people are motivated to do science for a translational value, and that’s important, but for me it’s more about the curiosity and solving an important problem that enhances our basic, fundamental understanding of how something in biology works. Pain is very mysterious and puzzling in how it works. From short term pain to longer lasting pain—what’s going on in our nervous system? What are the changes that permit or allow these long-lasting pain states? For me, I got into this work because I realized it’s an important question, a major health concern, and there are a lot more questions than answers. I like bringing different fields together and working with different types of people who look at the world scientifically differently and who have different strengths. We bring those together to tap into important questions—that really excites me about science.

What has been your favorite interdisciplinary collaboration?
I don’t know about a favorite one—maybe [our collaboration] with a computational neuroscientist. It’s interesting because there’s always a lot of tug-of-war and back-and-forth and trying to understand each other’s language to the best of your ability. At some point you just have to trust the other person’s expertise and they have to trust yours. I think collaborating with a computational neuroscientist has been a lot of fun—how they think about data and large datasets. I like the back and forth because we solve problems differently; for some of our studies, five mice are more than sufficient to compare different groups, but for a computational person they’ll say, “It’d be nice if I had five thousand trials of something to really be able to make a good model.” Trying to meet somewhere in the middle is challenging but also exciting.

What are you hoping to achieve with your research?
My ultimate goal is for us to increase knowledge and the knowledge of how this pain system works. For example, there’s one problem that’s really important that we haven’t solved yet: the mechanical pain sensor. There is a protein and ion channel, probably, that senses mechanical pain—if you’re hanging up a picture on the wall, and you accidentally bang the hammer into your thumb, it’s going to hurt like crazy at first, and that pain is immediate. How is that happening? What is the sensor in our body and our nervous system which is allowing that to occur? We haven’t identified that sensor yet. The ultimate goal for me is always to fill in gaps in knowledge in important problems, and hopefully some of those gaps that we fill will have translational and therapeutic value. If they do, that’s great, if not, it’s still important that we increase basic fundamental knowledge because the things that we learn could be applicable to another system or another problem that we can’t even foresee right now. So much of science—the biggest discoveries and the biggest breakthroughs that have had the most impact on human health—are discoveries made in different fields, discoveries where people were just curious about how something worked. Maybe some of the biggest, important health challenges of our time—cancer, or diabetes or heart disease, neurodegenerative diseases, or neuropsychiatric diseases, autism, dementia, clinical depression, etc—will come not from the people who directly study those things but from people in other fields.

What do you foresee as the next big step in your field?
I would answer that in two parts. One, the basic science is increasing at an exponential rate. I’ve told you we haven’t identified the mechanical sensor, but we have identified sensors for hot pain or cold pain, different parts of the brain that mediate certain aspects of a painful response, the sensory neurons that sense pain and how they feed into the spinal cord. The field is making progress on the basic science, and it appears we’ll continue to make that same type of progress. But a bottleneck or a limitation is that there hasn’t been too much output on the clinical side from all these basic science discoveries. Why hasn’t some of the research translated from the bench to the bedside as much as we would like? The models that we use to study pain—which are mainly rodents—are making all these cool discoveries, but a prerequisite for extracting value from those models is that we’re able to understand and interpret what an animal is experiencing. If we don’t know if the animal is in pain or relief from pain in our models, then how could any of that work translate to a human if the models we use to study it aren’t intact, if we don’t know what they’re telling us? So, if we have improvements in how we measure and assess pain in the pre-clinical models, then we’ll speed up the rate from which we go from the bench to the bedside. I think that’s where the field is moving.

What surprised you most about working in this field or in academia?
One thing that surprised me I think as a younger student coming up–you believe that scientists or medical practitioners know everything, and whatever you ask them they’ll be an expert on, which couldn’t be further from the truth and is something that I’ve learned, I am learning, and I see it in my own self. You become an expert in something that you’ve studied, but for most other things in science, you can be just as clueless as someone else. I think the public doesn’t appreciate that at all times—I know they don’t because sometimes they ask me “Oh you’re a scientist, you’re a researcher, what do you think about this? How about this finding?” I’m like, “No, I don’t know anything about that, because its outside of my field.” We are specialists—maybe to a fault, but that’s how things go these days—and I think that’s been sort of surprising and humbling.

What advice would you give someone just starting out?
I would say follow what you’re passionate and curious about, the thing that excites you every day, because that’s when you’re going to have fun and that’s when you’re going to be the most creative and make a really big impact. I go to bed thinking about ideas a lot of the time; sometimes I’ll wake up in the middle of the night and an idea will hit me, and that only happens because the things I’m working on I’m really passionate about. To make big discoveries, that’s the type of thinking required because a lot of time experiments don’t work, there’s a lot frustration in this business, and to really power through important problems requires a lot of hard work, dedication, and focus. So, with the first thing you work on, if you’re not excited in that lab, don’t stick around—tell the person “On paper I thought I would like this, but I don’t really like this, I’m going to try something else.” There’s enough out here you can find to be excited about, even if that isn’t science or medicine; maybe you like art or maybe you like to write, or you like public speaking. Figure out whatever that is and just spend all your time doing that.

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