Therapeutic applications as a motivating factor

Brown Engineering’s newest Assistant Professor Theresa Raimondo used the word infrastructure when asked why she landed back at Brown University to advance her academic career from student to teacher and researcher. The rising star in the burgeoning field of immunoengineering recognized the plethora of collaborations, not only with the faculty whose labs are near hers at 225 Dyer St., home to the new Brown RNA Center, but also the proximity of the local hospitals and the Legoretta Cancer Center. Access to clinical samples, cancer experts, and clinicians are key to the work she intends to do.  

“I’ve already been working with (Professor) Juan Alfonzo (of molecular biology, cell biology and biochemistry) to learn more about RNA modifications and RNA biology. Our goal is to build on the expertise of molecular biologists, including Professor Alfonzo, who have collectively identified more than 100 chemically-modified nucleic acids. These modifications have implications in human disease. By incorporating appropriate modifications into in vitro transcribed (i.e. lab made) RNA, my lab seeks to engineer the next generation of RNA therapeutics,” she said, underscoring how quickly she has managed to utilize Brown’s cross-disciplinary setting. Raimondo also holds a secondary appointment in the Division of Biology and Medicine, and is a member of both the Brown RNA Center and the Cancer Therapeutics Program within the Legorreta Cancer Center.

“My goal comes from my training,” she said, referencing her postdoctoral research at Massachusetts Institute of Technology’s Koch Institute for Integrative Cancer Research and her graduate work at Harvard with Professor David Mooney. “Dave is a leader in the fields of biomaterials, drug delivery, and immunoengineering — among other areas. While in his lab, I had the opportunity to work on biomaterials that could control the timing and spatial gradients of in vivo drug delivery; a concept that he has used in the context of tissue engineering and cancer vaccines. This work inspired me to think about how we could use materials to control the immune response to promote functional tissue regeneration. One of the main focuses of my doctoral research was the development of cytokine-conjugated gold nanoparticles that could control macrophage phenotype, and ultimately increase muscle strength following acute injury and in mice with muscular dystrophy. The research that I am starting at Brown will continue working toward this goal: Can we modulate the immune system for clinically beneficial therapeutic purposes?

“In my postdoc, I continued to focus on macrophage modulation, however now in the context of cancer immunotherapy. Rather than promoting regenerative phenotypes, my focus was to promote cancer killing phenotypes. Many people think of cancer when they hear immunotherapy. What I find fascinating though, is that the immune system can both kill cancerous cells or promote tissue regeneration if it is given the right cues,” she said.

“My vision is to engineer drug delivery therapeutics for immune modulation on both sides of that coin: functional tissue regeneration and cancer immunotherapies. What can we do to help people?”

Scientists have known about RNA, the ribonucleic acid that is a copy, or transcription, of DNA, for some time. But the new push to use it therapeutically, Raimondo says, is because of both the chemical modifications that have been discovered to make it stable and not inflammatory, and the development of nanoparticles capable of delivering RNA in vivo. Drew Weissman and Katalin Kariko were awarded the 2023 Nobel Prize in Medicine for the RNA modification work that culminated in the development of effective mRNA Covid-19 vaccinations during the pandemic that began in early 2020, and one reason science is turning anew to RNA.

“Both of my postdoctoral advisors, Professor Robert Langer and Professor Daniel Anderson, played integral roles in the development of lipid nanoparticles that enable therapeutic RNA delivery. My postdoctoral research built on this nascent platform technology to develop novel siRNA — lipid nanoparticle based cancer immunotherapies. I’ll continue this line of research at Brown, focusing on how to deliver RNA such that it is targeted to the right organs and the right cells so that it is a useful therapeutic.”

Along with her active laboratory (which Raimondo has begun filling with a pair of master’s students and with two Ph.D. students), she also co-taught the undergraduate biomedical senior capstone design course in the spring and will be co-teaching biomaterials (ENGN 1490) in the fall. Looking forward, she plans to develop a new immunoengineering graduate level course. 

“This course is not currently offered at Brown. Immunoengineering is an emerging field. A former colleague at Harvard, now at the University of Delaware, is in the process of establishing the same course. Other institutions, such as Johns Hopkins, are also establishing immunoengineering programs and I plan to bring this exciting discipline to Brown. Immunology is typically not taught in traditional engineering programs, and required considerable self-education on my part. As science and engineering become more complex, the importance of interdisciplinary education and collaboration has never been more vital.”

Meanwhile, she continues making collaborative strides with other campus partners, like Assistant Professor of Biostatistics Ying Ma. Ma is working on computational challenges in genomics and genetics, particularly single-cell RNA-sequencing. “Computational modeling, and machine learning, is a really rich way to process large amounts of (RNA) expression data, and importantly test hypothesizes in silico,” Raimondo said. “The ability to test therapeutic interventions, with these innovative predictive models will allow me to rapidly screen RNA-based therapeutics, and substantially increase the pace at which novel therapeutics are developed. Two computational researchers, Professor Ma and Professor Xubo Yue at Northeastern, and I recently submitted a proposal for NSF funding to work on this collaborative project.  It’s a rather new technology. We're trying to push the boundaries of computational modeling, and innovate new ways that this computational power can be used for therapeutic design and validation.”

Just as she began her new position on College Hill, Raimondo was announced as a finalist in the 2023-24 MIT-Royalty Pharma Prize Competition, a competition for female faculty entrepreneurs in biotechnology. She continues to address that viable project in her lab. On the heels of that honor, in March, she was awarded American Cancer Society Institutional Research funding, a pilot grant supporting junior faculty seeking to initiate cancer research projects.  

Prior to earning her Ph.D. in engineering sciences-bioengineering from Harvard in 2019, Raimondo was a 2011 (chemical and biochemical engineering) graduate of Brown. “I loved being a student here,” she said. “I always say the whole world came to me at Brown, scientifically and culturally, and everything. It was a wonderful undergraduate experience, and I am thrilled to be back at Brown!”