Stefani Spranger is exploring multiple avenues for the next immunotherapy breakthrough
Pamela Ferdinand | Spectrum
March 12, 2019
A YOUNG LAB AT THE FOREFRONT OF IMMUNOTHERAPY DISCOVERIES is an exciting yet challenging place to be. MIT faculty member Stefani Spranger, an expert in cancer biology and immunology, understands that better than most people.
Spranger knows that new labs such as hers, which opened in July 2017 at the Koch Institute for Integrative Cancer Research at MIT, face distinct advantages and disadvantages when it comes to making their mark. While younger labs typically have startup grants, they lack the long-term funding, track record, and name recognition of established researchers; on the other hand, new labs tend to have smaller, close-knit teams open to tackling a wider array of investigative avenues to see what works, what doesn’t work, and where promise lies.
That’s when the funds and recognition of an endowed professorship can make a big difference, says Spranger, an assistant professor of biology who last year was named the Howard S. (1953) and Linda B. Stern Career Development Professor. “Not everything will work, so being able to test multiple approaches accelerates discovery and success,” she says.
Spranger is working to understand the mechanisms underlying interactions between cancer and the immune system—and ultimately, to find ways to activate immune cells to recognize and fight the disease. Cancer immunotherapies (the field in which this past year’s Nobel Prize in Physiology or Medicine was awarded) have revolutionized cancer treatment, leading to a new class of drugs called checkpoint inhibitors and resulting in lasting remissions, albeit for a very limited number of cancer patients. According to Spranger, there won’t be a single therapy, one-size-fits-all solution, but targeted treatments for cancers depending on their characteristics.
To discover new treatments, Spranger’s lab casts a wide net, asking big-picture questions about what influences anti-tumor immune response and disease outcome while also zooming in to investigate, for instance, specifically how cancer-killing T cells are excluded from tumors. In 2015, as a University of Chicago postdoc, Spranger made the novel discovery that malignant melanoma tumors with high beta-catenin protein lack T cells and fail to respond to treatment while tumors with normal beta-catenin do.
Her lab focuses on understanding lung and pancreatic cancers, employing a multidisciplinary research team with expertise ranging from immunology and biology to math and computation. One of her graduate students is using linear algebra to develop a mathematical model for translating mouse data into more accurate predictions about key signaling pathways in humans.
Another project involves exploring the relationship between homogenous tumors and immune response. Not every cancer cell is identical, nor does it have the same molecules on its surface that can be recognized by an immune cell; cancer patients with a more homogenous expression of those cells do better with immunotherapy. To investigate whether that homogeneity is due to the tumor or to the immune response to the tumor, Spranger is seeking to build a model system. The research involves a lot of costly sequencing—up to $3,000 per attempt, which is fairly expensive for a young lab—and each try has an element of what Spranger half-jokingly describes as “close your eyes and hope it worked.”
“Being able to generate preliminary proof of concept data for high-risk projects is of outstanding importance for any principal investigator,” she says. “However, it is particularly important to have freedom and flexibility early on.”
Advancing cancer research and supporting the careers of promising faculty were the intentions of Linda Stern and her late husband Howard Stern ’53, SM ’54, whose gift has supported a series of biology professors since 1993. The first appointee to the chair was Tyler Jacks, now director of the Koch Institute.
Linda Stern says her husband, the cofounder and chairman of E-Z-EM, Inc., and a pioneer in the field of medical imaging, gave thoughtfully to many charitable causes. Yet MIT, where he earned undergraduate and graduate degrees in chemical engineering, had a special place in his heart.
“He was very involved and loved MIT,” says Stern, whose own career path included working as a private detective for 28 years. “He made wonderful contacts and got a wonderful education. He was a real heavy hitter when it came to defending the university.”
MIT’s continued excellence in a competitive environment depends on its ability to recognize and retain faculty, nurture careers, support students, and allow for the pursuit of novel ideas. Like the full professorships awarded to tenured faculty members, career development professorships such as the one endowed by the Sterns fund salary, benefits, and a scholarly allowance. These shorter-term (typically three-year) appointments, however, are specifically meant to accelerate the research and career progression of junior professors with exceptional potential.
“The professorship showed me that MIT as a community is invested and interested in fostering my career,” says Spranger. The discretionary funds she receives from the chair can cover, without need for an approval process, expenses that are not paid for by grants or that suddenly arise from a new idea or opportunity. They can keep projects running in tough times, fund travel to conferences, and purchase equipment. “It gives you a little more traction,” Spranger says. “It’s probably the best invested money because you have a lot of ideas you want to test, and at the same time, you are still checking the pulse of where the field might go and where you want to build your niche.”