The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as professionals, and their collaborations at the Wyss Institute and beyond.
In 2018, Sanjid Shahriar started developing two new skills: powerlifting and computational biology. Each was started with an initial goal of complementing things he already possessed: physical health and wet lab abilities. Honing both skills required determination and a desire to improve every day, and both have stood the test of time. Now, in addition to going to the gym five days a week, Shahriar is a full-time computational biologist in the Brain Targeting Program. He utilizes large datasets to identify potential targets that can be used as transport shuttles, ultimately helping therapeutics reach the brain. Learn more about Sanjid and his work in this month’s Humans of the Wyss.
What are you working on?
I’m a computational biologist on the target discovery team of the Brain Targeting Program. The brain is a highly protected organ. That makes sense, because as the control center of the body, you wouldn’t want viruses or bacteria to be able to enter easily. However, there are mechanisms in place to allow glucose, amino acids, and other essential nutrients that the brain needs to pass through its defense, the blood-brain barrier (BBB). So, we’re trying to identify these specialized proteins that can go from one side of the BBB to the other, so we can harness them to deliver therapeutics, which currently have a hard time crossing the barrier.
My job, specifically, involves examining large datasets related to the brain and identifying potential target molecules that can be used as transport shuttles, which the team working in the wet lab can then test. Their work allows us to develop antibodies to bind to target proteins, which can carry drugs developed by our sponsors across the blood-brain barrier.
What real-world problem does this solve?
The BBB is effective at keeping out dangerous pathogens; however, it is so effective at its job that most therapeutics for brain diseases cannot enter, resulting in drug failures in clinical trials. Our goal is to develop a transporter that is ubiquitous, allowing for the transport of various drugs for multiple diseases across the BBB. Right now, we’re focused on neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS, but eventually we could look at glioblastoma and other brain cancers. Once we have the platform, it will be broadly applicable.
What inspired you to get into this field?
I always knew I wanted to do disease research. We think of the human body as a well-oiled machine, but then, there’s an unexplained kink in the system, and everything starts to go haywire. My curiosity led to a desire to parse out what goes on mechanistically, discover why things are in disarray, and reverse engineer it to fix the problem.
We think of the human body as a well-oiled machine, but then, there’s an unexplained kink in the system, and everything starts to go haywire. My curiosity led to a desire to parse out what goes on mechanistically, discover why things are in disarray, and reverse engineer it to fix the problem.
I entered my Ph.D. program intending to conduct cancer research. After my first two rotations in cancer research labs, my program director suggested I branch out and see what other diseases piqued my interest. My third rotation was in a vascular biology lab focused on diseases associated with the blood-brain barrier, and I fell in love with the lab itself and the work being done there. The brain’s complexity fascinated me, and working to unravel its mysteries was both stimulating and profoundly satisfying.
During my Ph.D., most of my work was in the wet lab. In 2018, my mentor noted that transcriptomics, the study of RNA molecules within a cell, was becoming increasingly popular. He suggested I incorporate that into my work. So, I started learning more computational techniques and got a second mentor to guide me. It was amazing to parse out big data, generate hypotheses, and go into the lab to test them. This process felt like the right sequence of events, instead of feeling like you’re going into the lab blind. Now, incorporating coding and data into biology seems normal, but at the time, it was pretty novel.
What continues to motivate and excite you?
During my Ph.D., I found that the prospect of discovering new things and being at the forefront of innovation is a huge motivator. People used to think that angiogenesis, the process of forming new blood vessels from existing ones, started in the capillaries, the smallest blood vessels. My data showed that the veins are actually the source of angiogenesis. Realizing I was one of the first people to discover this was amazing. You get this incredible feeling of achievement. That, along with scientific curiosity, keeps me excited and motivated.
What are some of the challenges that you face?
The fact that most of my Ph.D. work was in a wet lab sometimes poses challenges. Since I didn’t have a lot of formal bioinformatics training when I started at the Wyss, learning new computational techniques or developing code took me a bit more time than it would someone with more experience. Luckily, I’ve had great mentors, and this doesn’t pose as much of a challenge anymore.
In other instances, this is even an advantage. For example, when we have lab meetings and colleagues discuss an in vivo experiment, I can troubleshoot and offer suggestions. Additionally, when I conduct analyses, I appreciate the underlying biology. There are times when the data shows something is a potential target of interest, but it doesn’t make sense from a biological perspective. My experience in vascular biology provides me with this understanding.
Why did you want to work at the Wyss?
While I was doing my Ph.D., I made it clear to my mentor that I wanted to go into industry because I thought the research was more efficient, goal-oriented, and streamlined. I realized that the drawback is that there is less freedom to explore than there is in academia. The Wyss is at the intersection of these two worlds, so I knew by joining, I could have some flexibility while in an environment that was more structured. I was also excited to meet the challenges of a fully computational role.
What is unique about the Wyss? How has that impacted your work?
People’s willingness to help has had a profoundly positive impact on my work, enabling me to continue growing and learning.
I’ve been at the Wyss for more than three years now, and what I’ve found to be unique is that researchers here have a wide range of expertise and are very open to collaboration. People’s willingness to help has had a profoundly positive impact on my work, enabling me to continue growing and learning. For example, Viktor Horvath was my first computational mentor. He always carved out time to meet with me. Even though Bogdan Budnik is very busy, he is more than happy to talk things through and offer support around proteomics.
How do you collaborate with and receive support from other teams at the Wyss?
In addition to the support from individuals like Bogdan, I am lucky enough to be part of the Translational AI Catalyst, led by Megan Sperry and Ally Chang. Those of us doing computational work across different groups at the Wyss have regular meetings where we discuss what we’re working on and can troubleshoot together.
What do you like to do outside of work?
I love listening to audiobooks — I’m a big fantasy fan, and Brandon Sanderson is my favorite author. I also really enjoy David Sedaris for something a bit lighter and funnier. Outside of that, I love spending time with my daughter — playing games, going to the park, and taking her on playdates. In the evenings, after we put her to bed, my wife and I like to unwind by watching TV together.
One of my biggest hobbies is lifting weights. I started back in 2018, originally just trying to get healthier, but it’s become a real passion. These days, I aim to get to the gym five days a week, always trying to push myself a little further. Powerlifting has taught me discipline and consistency, and I try to bring that same mindset of steady improvement into my work as well.
If you had to choose an entirely different career path, what would it be?
I’d probably be in tech or finance, working as a software engineer or a data analyst. When I started to incorporate more computation into my work, I realized I really like using coding to solve problems.
What does it feel like to be working on cutting-edge technologies that have the potential to have a real and significant impact on people’s lives and society?
When I discover something new, I imagine it feels similar to how explorers felt many years ago when they set foot in a new land…Then you consider the fact that these discoveries have the potential to improve medicine and treat diseases that have plagued humanity for a long time, and it is truly exciting.
I approach science from a place of curiosity and fun. When I discover something new, I imagine it feels similar to how explorers felt many years ago when they set foot in a new land. Growing up as a nerdy kid, I think this is the closest I’ll get to feeling cool. Then you consider the fact that these discoveries have the potential to improve medicine and treat diseases that have plagued humanity for a long time, and it is truly exciting.