Taubman Emerging Scholar Award Supports New Strategies to Make Small Cell Lung Cancer Visible to the Immune System
By Lynn McCain | July 29
Less than two years after arriving at the University of Michigan, physician-scientist Navin Rajput Mahadevan, MD, PhD, has been named a Taubman Emerging Scholar, receiving five years of support to advance research aimed at improving outcomes for patients with small cell lung cancer, one of the deadliest forms of cancer.
Mahadevan, an assistant professor of pathology, will use the award to investigate how some small cell lung cancers become recognizable to the immune system and how that knowledge can be used to develop new treatments. The Taubman Emerging Scholar Award provides $50,000 annually for five years, funding laboratory supplies, reagents, and specialized analyses needed to move the project forward.
“Our overall goal is to understand how immune responses are raised against cancer,” Mahadevan said. “Small cell lung cancer serves as a powerful model because we now know there are distinct immunologic subtypes of the disease.”
Understanding “hot” and “cold” tumors
Previous research by Mahadevan and collaborators showed that small cell lung cancer could be divided into subtypes: an “immune cold” subtype that largely escapes immune detection, and an “immune hot” subtype that is recognized by the immune system and is more likely to respond to immunotherapy.
“If we can detect this immune-hot subtype in patient samples, we've previously shown that those patients actually respond to immunotherapy,” Mahadevan said.
The distinction is important because survival rates for small cell lung cancer remain poor. Even with current therapies, overall survival at two years is only about 10% to 20% for many patients. Patients whose tumors belong to the immune-hot subtype, however, can experience substantially better responses to therapies aimed at invigorating the immune response against cancer.
A promising target
Central to the project is a protein called IGF2BP1, which Mahadevan's laboratory has identified as a potential driver of the immune-hot phenotype. The protein is especially intriguing because it appears to be uniquely elevated in immune-responsive small cell lung cancers. Researchers believe it may help control tumor behavior by binding to messenger RNAs inside cancer cells.
“One part of the project is to understand what RNAs are being bound by IGF2BP1 and how that contributes to this immunogenic phenotype,” Mahadevan said.
The protein may also provide a direct target for immune-based therapies. IGF2BP1 is classified as an oncofetal antigen, a type of protein normally expressed during fetal development but largely silenced in healthy adult tissues. Because the immune system does not typically encounter these proteins in adulthood, their reappearance in cancer cells can make tumors more visible to immune attack.
Turning cold tumors hot
A major goal of the research is determining whether immune-cold tumors can be converted into immune-hot tumors. Mahadevan's team is testing epigenetic approaches that effectively rewrite gene-expression programs within cancer cells, potentially reactivating proteins such as IGF2BP1.
“It's a two-pronged strategy,” he said. “One would be to turn it on in these immune-cold subtypes and then get the immune system to recognize it. The other strategy would be to target it in the subtype in which it's already on.”
The researchers are also investigating whether these approaches can selectively affect cancer cells while minimizing effects on normal tissues, which is why his lab is especially interested in oncofetal antigens, which appear to be a tumor-specific target.
Searching for new therapeutic targets
Beyond IGF2BP1, the project includes an ambitious effort to identify the full range of protein fragments, or peptides, displayed on immune-hot small cell lung cancer cells. Working with collaborators at the University of Michigan, the team will conduct a comprehensive immunopeptidome analysis to determine exactly what the immune system recognizes on these tumors.
“We know that these tumor cells are recognized by the immune system,” Mahadevan said. “But we don't know what exactly is being recognized.”
The findings could reveal entirely new targets for future therapies, including cancer vaccines and engineered T-cell treatments.
Linking pathology and discovery
Mahadevan joined Michigan Medicine in October 2024 after completing postdoctoral training at the Dana-Farber Cancer Institute and serving as an attending pathologist at Brigham and Women's Hospital in Boston. As a molecular pathologist, he balances clinical service with research, spending approximately 20% of his time in patient-focused diagnostic work and 80% in the laboratory. He credits Michigan's physician-scientist environment with helping him translate observations from patient samples into research questions and, ultimately, potential new therapies.
“Being a pathologist physician-scientist here at Michigan really allows me the opportunity to bring findings from laboratory models back into patient samples,” he said. “It strengthens not only the research itself but also our ability to develop biomarkers that may predict which patients will respond to particular therapies.”
Supporting the next generation
The award comes at an important time for early-career investigators navigating an increasingly competitive federal funding environment.
“I really would like to thank the Taubman Institute for supporting junior investigators during a more difficult time in obtaining extramural funding, especially NIH funding,” Mahadevan said. “This support will accelerate my early career and help position us to compete for future federal awards.”
Now fully staffed and operating with a complete research team, Mahadevan's laboratory is poised to pursue the projects outlined in his Taubman proposal, bringing new momentum to efforts aimed at making one of the most aggressive cancers more vulnerable to immune attack.
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