The Humans of the Wyss (HOW): ATT Edition series highlights members of the Wyss Advanced Technology Team (ATTs), showcasing their role, their work, the influences that shape their approach, and their collaborations at the Wyss Institute and beyond. Reliant on strong technical expertise, diverse product development experience, and a focus on end-user needs, ATTs translate high-risk technologies into innovative solutions to advance society.
According to Sasha Stafford, you cannot understate the ability of science to impact huge numbers of people. He hopes to see the technologies he works on get from the bench to the bedside and have an incredible effect on people’s lives. At the Wyss, Sasha is working on a drug delivery platform technology using click alginate-based hydrogels. Learn more about Sasha and his work in this month’s Humans of the Wyss.
What are you working on?
I’m working on an Institute Project that’s a drug delivery platform technology using click alginate-based hydrogels. We use sodium alginate that’s cross-linked using click chemistry to form a covalent network with a low mesh size. Click chemistry refers to certain reactions that are easy to perform, take place in water, produce a high yield, and generate minimal byproducts. Using click chemistry, our team has crosslinked the sodium alginate in a way that allows us to manipulate the hydrogel matrix without interfering with any of the molecules (like proteins or cells) that are held within it.
Think of the hydrogel formed after the cross-linking like Jell-O with pieces of fruit in it. If you want to release the fruit from the Jell-O, you need to manipulate the bonds that hold the Jell-O together in order to allow the fruit to come out intact. In our case, the “fruit” is a drug. This system can essentially deliver any small molecule, biologics, nano-particles, or combination thereof.
What real world problem does this solve?
New drug delivery methods have held promise for several decades that has largely gone unrealized so far. Our approach circumvents a lot of the issues faced by previous methods. We can deliver drugs directly to the disease site, which allows us to reduce the dose needed and prevent off-target effects and systemic toxicity. This can also increase the efficacy of treatment due to our sustained and localized delivery. We hope to help drug delivery finally achieve the promise that’s been outstanding for so many years.
We have started by tackling more complex delivery sites, like the brain and the eye. Once we’ve shown the safety and efficacy there, we can then move on to other applications and delivery sites that we want to pursue that might be less challenging.
What is your role with the team?
I am a Staff Scientist and member of the Advanced Technology Team, or ATT. In that role, I’m really driving this click alginate project towards translation and serving as the institutional memory for a lot of the projects that are part of the Immuno-Materials Platform.
I’ve been here for ten years, so I’ve seen a lot of projects come and go. The Wyss is an interesting place because a project’s lifetime can be anywhere from six months to a couple of years. If something isn’t commercially translatable, it may be kicked back to the labs so the researchers can take another look and reengineer the technology. There’s an idea that if something doesn’t work, it may be able to be reinvented and then reviewed again for potential translation. Since I’ve seen this happen, I can be a resource to researchers and let them know what has and hasn’t worked in the past, so they don’t reinvent the wheel.
What is the biggest difference between working in industry and working at the Wyss?
In industry, I felt like I was just a cog in the machine. I worked on the same project day in and day out. At the Wyss, I’ve been fortunate enough to not only invent things, but contribute to novel technologies as well as their translation. Industry is oriented towards progressing a product through clinical trials whereas the Wyss works with technologies in the phases prior to that, which is so appealing to people that are more creative.
How are you and the other members of the Advanced Technology Team helping to bridge the gap between industry and academia at the Wyss?
Part of being on the Advanced Technology Team is knowing the standards of industry and working towards them on a daily basis. We’re familiar with regulatory criteria like GMPs, GCPs, and GLPs. One of our roles in de-risking technologies is to use our industry experience to elevate them, which helps them go beyond a publication or thesis and brings them to patients.
I know what it takes to get to a Phase 1 clinical trial, so I’m kind of working backwards from there, whereas someone with only academic experience may not know what you need to reach that milestone. Having an Advanced Technology Team with that knowledge working towards the goal of translation is the real advantage of the Wyss.
What else is unique about the Wyss?
The collaborative environment breeds a diversity of technologies and gives people the ability to combine them and make something novel. I’ve seen technologies that I don’t think would have come about without our cooperative atmosphere where the researchers work adjacent to each other, have a knowledge of other technologies we can access, and are able to chat and figure things out.
How do you collaborate with and receive support from other teams across the Wyss?
I’m part of tons of collaborations both internally and externally, including some with George Church’s lab, David Weitz’s lab, and a co-development program with an industry partner. I think at one point I had ten different collaborations! Another useful type of collaboration is with the local hospital and clinicians. Having access to them is paramount. They see needs that exist for patients and as engineers we could potentially fill that hole.
What is your biggest piece of advice for an academic scientist looking to translate their technology?
Talk to a lot of people – that will help you get a feel for the regulatory and translational landscape. Get as many different opinions as possible because there’s no one right way to do things, it’s all contingent on what technology you have. I always take the perspective that a good mentor won’t show you how to do things, they’ll point you in the right direction, and it’s on you to figure it out from there.
How did you become involved at the Wyss and what inspired you to get into this field?
During my time here at the Wyss, I have been afforded the opportunity to expand my scientific expertise. I was initially hired to support the Chemistry, Manufacturing, and Controls (CMC) section of the Investigational New Drug (IND) Application at Dana Farber for the melanoma cancer vaccine. We did work to validate the methods and production for that vaccine to support the clinical trial. Once the work was done, I moved on to a project for the treatment of peripheral artery disease using ionic cross-linked hydrogels. As this project progressed, I started working on our click-alginate technology in collaboration with Rajiv Desai, who was a graduate student in David Mooney’s lab at the time. We worked in parallel until his departure from the lab. Then I took over the project, moving towards the aforementioned Institute Project. During this time, I was obtained my Master’s in Bioengineering and Nanotechnology and was promoted to a Senior Staff Scientist.
The work on the melanoma vaccine inspired me to get involved in this area of work at the Wyss. The idea of a cancer vaccine was novel and exciting at the time. It was a big pivot from industry, but I liked the academic environment. The Wyss is a great place to bridge that gap between industry and academia. I felt like my skillset filled that niche, but I’m also someone who has transformed myself several times. I was originally an analytics person and have since become a biomaterials person and a drug delivery person, and now a manager.
What continues to motivate and excite you?
The potential to actually get things to bedside so that it’s really benefitting patients and alleviating their pain. Unfortunately, most people will face some health challenge at some point. The more that we can do to fix that, the better.
What are some of the challenges that you face?
Platform technologies are great, in that they provide a lot of potential. But, to get them to clinic you must pick the right indication, and that’s often difficult. The landscape is vast, and you have to pick a path to move forward. You worry that it might not be the right path, or that by choosing one way you might miss another opportunity that could be more substantial or more promising. I think finding that right indication and then sticking with it and continuing to work on it can be a challenge.
When you’re not at the Wyss, and you’re not social distancing, how do you like to spend your time?
I enjoy hiking outdoors and cooking. My favorite cuisines to cook are Indian food and Mexican food.
If you had to choose an entirely different career path, what would it be?
A cook. I’m a chemist by training so it translates well to the culinary arts. I prefer cooking more than baking – I don’t like recipes.
What does it feel like to be working towards translating cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?
It’s great – I mean, I think you can’t understate the ability of science to impact huge numbers of people. That’s really why I got into the field. A single invention or combination of inventions can impact hundreds of thousands of people. We’ve seen that recently with Moderna and Pfizer/BionTech creating something that is now impacting billions of people. Not a lot of other fields can do that.