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Investing in the promise of immunotherapy

For Rachel Weathered, PhD’22, the microscopic world has always been a source of endless fascination.

Her first encounter with it came in third grade when, channeling her best Antonie van Leeuwenhoek, she looked at a sample of pond water and discovered marvels—thousands of tiny creatures contained between two sheets of glass.

“I was so intrigued that I asked for one of those kids’ microscopes for my birthday,” Weathered said. “And it instantly became my favorite toy. I collected my own samples and looked at water, blood, and fruit flies under the microscope. I felt like an explorer and was gripped by a need to understand this new world.”

After completing an undergraduate degree in biomedical engineering, Weathered enrolled in a PhD program at the University of Chicago’s Pritzker School of Molecular Engineering, and it was here that she turned her focus to an issue long in her thoughts—cancer and autoimmune disease.

“I lost my grandfather to cancer when I was young and later lost an aunt to multiple sclerosis,” Weathered said. “Because of that, I’ve always wanted to make a real difference for people with those conditions. Immunoengineering gives me that opportunity, allows me to create tools and therapies that help people lead healthier, happier lives.”

Recreating the microscopic world

Under the mentorship of Melody Swartz, William B. Ogden Professor of Molecular Engineering, Weathered joined one of the nation’s preeminent labs focused on engineering immunotherapies—the Chicago Immunoengineering Innovation Center, part of Pritzker Molecular Engineering. For her, it was like being on the threshold of a new medical era with new immunotherapies like CAR T-cell therapy and immune checkpoint inhibitors emerging as potent alternatives in treating challenging diseases.

“To look at some of these studies and see the results, that some people are coming out of trials cancer-free, that’s exactly what we envision with the future of immunology, and it’s exciting,” Weathered said. “My goal now is to make sure these technologies get the attention they deserve so that our  approach to cancer and autoimmune disease is that much better in ten to twenty years.”

Weathered’s research centers on creating more accurate in vitro models of tumor microenvironments, which can be used to test new immunotherapies. Current models don’t fully reflect the conditions inside a living organism where multiple cell types interact with each other and their surrounding microenvironment. Because of that, researchers sometimes struggle to accurately gauge a therapy’s effectiveness in early development.

Weathered’s models, in comparison, are dynamic. They can simulate interstitial flow (fluid movement in a cellular environment) and host immune and stromal cells, providing more realistic conditions. Her work could someday allow researchers to dramatically reduce the development time of new treatments.

Beyond her work on test models, Weathered has also investigated lipedema, a condition that causes excess fat to accumulate in the lower part of the body.  She and her lab partners have coordinated with the Lipedema Foundation to analyze samples, study potential biomarkers and explore the role interstitial flow, extracellular vesicles, and lymphatic vessels might play in the condition’s progression.

Elevating treatments that work

Already interested in private industry, Weathered participated in two UChicago programs that she believes were instrumental in her career path. The first was a myCHOICE internship with Aspire Capital, and the second was the George Shultz Innovation Fund run by Polsky Center for Entrepreneurship and Innovation.

Through these two programs, Weathered learned how to perform due diligence on private and public companies, analyzing their underlying science. Both experiences gave her a new perspective, showing her the potential impact she can make both inside and outside of the lab.

“Firms hire PhDs as analysts because we’re good at teasing apart data, thinking critically about hypothetical problems, and asking hard questions,” Weathered said. “That was also one of my favorite parts of being a PhD student—constant learning and exploring—and I’m thrilled to take on a role doing it professionally.”

This fall, Weathered will begin work as a biotech investment analyst for UBS. She hopes that through her position, she’ll be able to help elevate promising new technologies that stand to make a real impact in the fight against cancer and autoimmune disease.

“As far as immunotherapy is concerned, I believe we're at the tip of the iceberg,” Weathered said. “I think we’ll see therapies that will be safer and more personalized. I think we’ll have better screening, so we’ll know what patients will respond to, and physicians will have a much better toolkit to predict and prescribe the best course for each patient. It's exciting, and I’m looking forward to helping those therapies get to the people who need them.”