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 sailing and in science, it’s important to communicate and stay calm in stressful situations, which is something postdoctoral fellow Sarah Sandler knows well. As a competitive sailor, she has raced all over the world and in difficult conditions, where things change quickly. At the Wyss, she is taking on a different type of challenge: developing NanoDEX, a nanopore-assisted therapeutics discovery platform for historically difficult-to-drug targets, and working towards its translation. Learn more about Sarah and her work in this month’s Humans of the Wyss.
What are you working on?
I’m working on NanoDEX, a platform that helps discover drugs for targets that the pharmaceutical industry has historically struggled to screen. Many disease-relevant proteins, or targets, are considered “undruggable” because they are flexible, lack obvious binding pockets, or don’t have stable structures that conventional tools can easily model.
NanoDEX uses nanopore-based single-molecule measurements to directly read out how millions of molecules interact with these difficult targets. That gives us both hit discovery, meaning the ability to identify promising molecules that interact with a biological target in a therapeutic way, and the high-quality kinetic data needed to train AI models for lead optimization.
Recently, NanoDEX was renewed as a second-year Validation Project, and I am excited to keep advancing this technology towards translation.
What real-world problem does this solve?
Our first application is focused on intrinsically disordered proteins in neurodegenerative disease, where these flexible proteins can form toxic aggregates, or dangerous and misfolded clumps, that are difficult to measure and target with conventional drug-discovery tools. In this case, the conformation, or specific shape, of the protein is relevant to the disease’s toxicity. Having a tool like NanoDEX for high-throughput screening of different conformations of proteins is essential. We are identifying new compounds that could bind to these intrinsically disordered proteins and exert a therapeutic effect.
What inspired you to get into this field?
Growing up by the water on Long Island, I was fascinated by horseshoe crabs. I learned that their blood contains amebocytes, immune cells that detect bacterial toxins and cause blood clotting in their presence to smother the threat. Because of this, they have been harvested excessively, and many species of horseshoe crab are now endangered. I got involved with research in high school, motivated by my desire to help protect them.
As I continued to dive deeper into science, I became interested in using nanotechnology to understand biology at the scale where molecular interactions actually occur. When I got to college, I trained as a materials science engineer and then did graduate work in nanoscience and nanotechnology as well as biophysics, so my work has always been grounded in how materials, molecules, and biological systems interact at very small scales.
During my Ph.D. and postdoc, I kept returning to the same idea: nanopores are an incredibly flexible way to measure biology. I explored different applications, first around nucleic-acid and protein interactions, and then I started thinking about how the same principles could be applied to drug discovery. That felt like a natural next step because so much of drug discovery depends on measuring whether molecules interact with a target, and for many difficult targets, those measurements are still really hard to make well.
What continues to motivate you?
I’m motivated by the idea that better measurement tools can unlock better medicines. I’ve seen repeatedly that important biology is often limited by the tools we have to study it. NanoDEX grew out of that realization. If we can directly measure molecular interactions that conventional technologies struggle to measure, we may be able to expand what biology we can drug, especially in diseases where patients still have limited options.
What excites you most about your work?
What excites me most is that NanoDEX brings together several things I care about: nanoscale measurement, difficult biology, AI, and drug discovery. I’ve always thought nanopores were a really powerful tool because they can measure molecular interactions directly at the single-molecule level. It is exciting to take that capability and apply it to targets that have historically been hard to screen.
The AI side is especially exciting because it makes this much more possible than it would have been a few years ago. Nanopores generate rich but complicated signals, and newer models give us a way to analyze those signals at a scale and depth that was not really possible before. That means we can start to think about the platform not just as a way to find hits, but as a way to learn from the data and design better molecules over time. The combination of high-quality experimental interaction data and AI-driven analysis is one of the most powerful parts of NanoDEX.
What are some of the challenges that you face?
The biggest challenges are around scaling and productization, which are exactly the areas we are focused on now. Scientifically, we are continuing to increase throughput while preserving the high-quality signal that makes the platform valuable. Computationally, we are building models that can identify binding patterns across large nanopore datasets and improve as more data is generated. From a company-building perspective, the key next step is packaging the platform into a workflow that pharma partners can easily understand, validate, and adopt. These are real challenges, but they are also clear engineering and execution problems, and our early data gives us a strong foundation to build from.
Why did you want to work at the Wyss?
I first became interested in the Wyss during my Ph.D. A postdoc I worked with early on, Nicole Weckman, left Cambridge University to join the Wyss and work with Jim Collins. When we caught up, she told me about the environment there and how people would sit in the kitchen over lunch, coming up with company ideas. She described this really collaborative community where people were not just doing great science but also thinking seriously about how to turn it into something useful.
I wanted to be somewhere where people were excited about both the science and the translation, and where starting a company from academic work felt like something people actually did.
That stuck with me. Pretty early in my Ph.D., I knew I wanted to be in a place like that. I wanted to be somewhere where people were excited about both the science and the translation, and where starting a company from academic work felt like something people actually did.
What is unique about the Wyss? How has that impacted your work?
The community is what feels most unique to me. Trying to translate a technology into a company is really hard, and there are a lot of moments where experiments do not work, or the next step is not obvious. At the Wyss, I have many friends and colleagues who are also trying to do this, which makes the whole process feel much less isolating. Being around people who are building companies, thinking about translation, and dealing with similar challenges makes it easier to keep going when things get difficult. It is a very unusual environment because people understand both the technical and company-building sides.
How do you collaborate with and/or receive support from teams across the Wyss Institute?
I work a lot with Ken Carlson, the Senior Director of Translational R&D, and he has been a true mentor to me. He has helped me understand how therapeutic development works and how to think about the experiments that will matter for translation. That has been essential because, as a scientist, it is easy to get excited about a technically interesting experiment, but building a platform means thinking carefully about which data will move the project forward.
I work with the Business Development Team, which has helped me think through partnerships, commercialization strategy, and how to communicate NanoDEX to external audiences. I’ve also joined the Translational AI Catalyst at the Wyss, which connects people working with large datasets, machine learning, and computational methods. This has been especially useful as more of NanoDEX depends on using AI to analyze complex nanopore signals.
How have your previous work or personal experiences shaped your approach to your work today?
My background has made me very comfortable working across fields. Materials science, nanotechnology, physics, biology, and engineering all come at problems in different ways, and NanoDEX really needs pieces of all of them. I think my training keeps me from being intimidated by problems that do not fit cleanly into a single discipline.
Materials science, nanotechnology, physics, biology, and engineering all come at problems in different ways, and NanoDEX really needs pieces of all of them. I think my training keeps me from being intimidated by problems that do not fit cleanly into a single discipline.
It also shaped how I think about measurement. A lot of my work has been about trying to understand interactions that are happening at very small scales. I think that has made me appreciate how important the right tool can be. Sometimes the biology is there, but we do not have the right way to measure it clearly enough. That is a big part of how I think about NanoDEX.
What do you like to do outside of work?
Outside of work, I’m an avid competitive sailor. I race on larger boats and have competed around the world. In May, I raced from the Cape to Nantucket, and earlier in June, I raced from Connecticut to Block Island. During my Ph.D., I did the Rolex Middle Sea Race, a five-day race around Sicily, and I helped deliver boats across Europe. I have my Royal Yachting Association Yachtmaster Certification, so I’m licensed to charter boats and have done fun cruising trips with friends in countries like Greece and Croatia.
1/5 Sarah is an avid competitive sailor. Credit: Sarah Sandler 
2/5 Sailing as part of a team has taught Sarah a lot about leadership, staying calm in stressful situations, and communication. Credit: Sarah Sandler 
3/5 Sarah has been able to travel by boat around countries like Italy, Greece, and Croatia, sometimes for sailing races and other times for leisure. Here she is pictured cruising in Malta after the Rolex Middle Sea Race. Credit: Sarah Sandler 
4/5 Sarah races as part of a team in Boston, most recently on the boat Murmur in the Figawi Race on the Massachusetts coast. Credit: Sarah Sandler 
5/5 Sarah has been racing competitively since she was younger. Here she poses with two early trophies. Credit: Sarah Sandler
Sailing has taught me a lot about leadership, staying calm in stressful situations, and communication. When you are offshore or sailing in difficult conditions, things can change quickly, and everyone has to work together. I think that has influenced how I approach stressful situations in science and company-building.
What’s something unique or fun about you that someone wouldn’t know from your resume?
I love long-distance hiking and backpacking! Last summer, I hiked the John Muir Trail, which is about 220 miles from Yosemite to Mount Whitney, and Mount Whitney was one of the hardest physical challenges I’ve ever done. This summer, I’m hiking the West Highland Way in Scotland, which is about 100 miles. I usually do these trips with one of my close friends from undergrad, and we get into a real rhythm on the trail. In some ways, the trips are almost more mentally challenging than physically challenging. You spend so much time managing discomfort, uncertainty, weather, and exhaustion, but also just continuing to move forward. I like having that kind of challenge outside of science because it gives me something completely different to focus on.
1/4 Sarah loves long-distance hiking and backpacking. Last summer, she hiked to the top of Mt. Whitney, one of the hardest physical challenges she's ever done. Credit: Sarah Sandler 
2/4 Mt. Whitney is the highest peak in the continental United States. Here, Sarah enjoys the sunrise on the mountain. Credit: Sarah Sandler 
3/4 Hiking Mt. Whitney was part of a 220 mile hike of the John Muir Trail, starting in Yosemite. Credit: Sarah Sandler 
4/4 While hiking is challenging, Sarah is rewarded by views like this. Credit: Sarah Sandler
If you had to choose an entirely different career path, what would it be?
I used to always think I would choose marine biology. It would let me combine my love of the ocean with discovery. I imagine going on scuba diving expeditions, finding new organisms, and then bringing samples back to the lab to sequence them, probably using nanopores.
Recently, though, I was working on a grant with Lyle Ostrow, one of the leading experts in ALS, and it made me think differently. I was really impressed by how deeply he understood both the science and the patients, and how closely connected he was to both. It made me understand the appeal of medicine in a new way. As a scientist, especially working at the earliest stages of technology and drug discovery, the path to patient impact can be long. I think it must be incredibly rewarding to see that impact more directly and immediately.
What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?
It feels exciting, but also a little intimidating. On one hand, it is really motivating to work on a technology that could change how we discover drugs for difficult targets. There is great potential in building something that could significantly impact the lives of patients with diseases for which current options are limited.
I have to focus on the next piece of data we need and the next problem we have to solve, but it is the bigger goal that really keeps me motivated and pipetting every day!
At the same time, early-stage science is very uncertain. There is still a lot to prove, and every step requires careful experiments and extensive troubleshooting. I have to focus on the next piece of data we need and the next problem we have to solve, but it is the bigger goal that really keeps me motivated and pipetting every day!