August 29, 2025 PhD student pushes CRISPR-edited CAR-T cells closer to the clinic Written By: Tom Ziemer Departments: Biomedical Engineering Categories: Research|Students As an undergraduate chemical engineering student at Villanova University, Anna Tommasi took a course in cell engineering that spurred her interest in developing biomedical therapies. It was the start of a path that’s led the native of western New York to the University of Wisconsin-Madison and the lab of Krishanu Saha, a professor of biomedical engineering and faculty member with the Wisconsin Institute for Discovery on campus. After getting an introduction to topics like CAR-T cell therapies and the CRISPR gene-editing tool in her course, Tommasi joined a research lab at Villanova, spent a summer working in a lab in France, and then accepted a graduate admissions offer at UW-Madison. Anna Tommasi. Photo: Joel Hallberg. Now in the fourth year of her PhD in biomedical engineering, she was the lead author of a paper published in March 2025 in the journal Molecular Therapy Methods & Clinical Development that outlines the Saha lab’s technique for nonviral production of CAR-T cells using gene editing and electroporation (electrically shocking the cells). CAR-T cells are modified versions of the body’s natural immune cells that have proven useful in treating various cancers and other diseases, including autoimmune disorders. Saha’s lab has worked closely with researchers at the UW-Madison School of Medicine and Public Health to advance CAR-T cell therapies that are modified at the genetic level. They aim to start new trials for brain cancers next year. As part of that line of research, UW-Madison and cell-therapy manufacturer Cellares announced a strategic collaboration in April 2025 to automate gene-edited CAR-T cell production. Tommasi, who’s helping to develop the production process in tandem with the Cellares team, and Saha flew to New Jersey to visit the company’s facility there in August 2025. “I’m a chemical engineer by nature, and we are taught how to think about, take apart and analyze processes to improve upon them, so process development and optimization are like my bread and butter,” she says. We caught up with the PhD student just before she visited Cellares to talk about her research and her graduate school experience at UW-Madison. How and why did you choose UW-Madison for graduate school?“When looking for grad schools, I was really interested in looking at labs that were focused on cell engineering and the translational aspect of it. I didn’t want to focus on foundational research—I wanted to learn more about the applicable, bench-to-bedside aspect of the field. So, I was so excited when I found Kris’ lab, because that was something very unique to his lab: applying the cell therapies that they were producing versus only focusing on understanding the underlying mechanisms behind the science. Basically, Kris values pushing the science conducted in his lab toward the clinic, which is what I was looking to get experience in.” What are some of the biggest remaining challenges in getting your group’s method from the research lab to the clinic?“A lot of it is trying to translate the process that we developed in our lab at a benchtop scale to Cellares’ large-scale machine. Anytime you transfer the CAR-T cell manufacturing process to a new instrument, things will change and so process parameters will need to change. Up until this point, it’s a lot of process-development meetings, because the Cellares instrument is located in California, not here in Wisconsin with us. That’s what I’ve been doing the past few years in lab—translating our manufacturing process to other devices that we have in the lab. And so, I’m in tune with how you have to change the parameters, and the different parts of manufacturing nonvirally that you need to change, in order to have your process be successful on a different instrument. So, the biggest challenge so far has been describing and characterizing our manufacturing process well enough so that someone in California can replicate what we’ve developed in Wisconsin and then fine-tuning the process with them on their machine in order to make sure that our process still is successful on their device and can efficiently manufacture CAR-T cells.” Anna Tommasi works with her PhD advisor, Professor Krishanu Saha, in the lab in the Discovery Building on the UW-Madison campus. Photo: Joel Hallberg. What do you hope your research leads to?“Honestly, I got into this work because I really love helping people, as cliche as that sounds. And I have always had this love for science and chemistry and puzzles; growing up, I always loved those chemistry kits for kids and, to this day, I still do the weekly Wall Street Journal Crossword Contests. And so, just physically being in the lab, getting hands-on experience with CAR-T cell manufacturing and seeing how CRISPR-Cas9 works in real life is really fascinating to me. I feel like my purpose is to help other people and hopefully give them a new lease on life, and while I can’t do that necessarily as a doctor, because I get squeamish thinking about blood, lab work is a close second—not being in the clinic, but helping progress real, effective therapies to the clinic so that maybe someone could get another chance at life beyond their disease.” What are your career plans or aspirations?“Great question—I don’t really know. I’m hoping that gaining experience in both benchtop research and seeing the process scale-up through to the bedside will give me a certain skillset that is valuable in industry—seeing the two different sides of actually getting academic research into the clinic. There seems to be a bit of a gap between academic research and industry that I think could be bridged to allow for more application of academic research in the industry setting. So, the skills I’m learning now will hopefully set me up well to find a position that makes it easier to translate academic research to industry for clinical use. I have also always really loved teaching and mentoring others; my first job at 14 was as a ski instructor, which I kept up through 2022. So, being able to impart what I’ve learned to others while also learning from others is something I really value and would look for in future positions. Bottom line: As long as I’m in a career that could potentially improve the quality of life of someone living with disease, that would be incredibly fulfilling.” What have you enjoyed about your time in Madison?“Wisconsin is actually really similar to upstate New York, environment-wise. I’m an avid skier, so I’m a huge snow fan and really don’t mind the cold, which is also why when I heard from Wisconsin, I was like, ‘Oh, that sounds great!’ Aside from the weather, I’ve enjoyed my time in the lab itself. Everyone from the other grad students to the staff scientists to the undergrads are so great. Everyone is so helpful and we want each other to succeed. We all bounce ideas off of each other and it’s a really collaborative environment, which I really value and appreciate.” Anna Tommasi, second from left, toured a Cellares facility in New Jersey along with Professor Krishanu Saha, second from right, and collaborator Christian Capitini, far left, a professor in the UW-Madison School of Medicine and Public Health. Submitted photo.