Fall 2025
By Kathy Clute
Photography by Sam Ogden
The G. Harold and Leila Y. Mathers Charitable Foundation has awarded Dana-Farber $1.47 million to support two Institute researchers investigating how cancer develops and how cells detect and respond to viral infections.
“We believe that transformative breakthroughs in cancer will come from a thorough understanding of the fundamental mechanisms by which it arises and grows,” said Zach Handelman, vice president and treasurer of the Mathers Foundation. “We feel privileged to fund this work at Dana-Farber and look forward to the new knowledge it will generate.”
Since 1991, the foundation has invested more than $17 million in basic and translational research at the Institute. The 2024 grants were awarded to microbiologist Philip Kranzusch, PhD, and pediatric oncologist David Pellman, MD, Margaret M. Dyson Professorship in Pediatric Oncology at Harvard Medical School.
Kranzusch’s team is investigating how cells respond to viral pathogens and how those signaling pathways can be harnessed to create potential new therapies for cancer and autoimmune diseases. “Human cells have a set of protein sensors that detect viral infections and quickly trigger immune responses,” said Kranzusch. “Interestingly, key components of antiviral immunity evolved billions of years ago in bacteria as mechanisms to defend against viruses called phages.”
The lab aims to understand how two bacterial defense systems work together to prevent phages from reproducing, possibly by forming complex structures that degrade viral DNA. The research team has discovered human immune genes with structural similarities, which may enable them to identify previously unknown proteins that play a role in the human immune response to viral infections.
Pellman and his colleagues study cell division and chromosome segregation errors in cancer and the impact of these faults on cancer genome structure. Nuclear atypia—unusual changes in the size and shape of cell nuclei—are a common feature of many tumors and have been used since the 1920s to assess tumor severity and predict outcomes. Previous research funded by the Mathers Foundation has found that these nuclear changes significantly affect genome rearrangements in human cancers.
It is possible that DNA changes and shifts in gene expression in atypical nuclei might be influenced by the formation of nuclear bodies around chromosomes after cells divide. Pellman is using advanced single-cell genomic technologies developed in his lab to zero in on specific nuclear bodies known as MN/53BP1, which are part of the cell’s response to DNA damage. A better understanding of how cells respond to DNA damage could lead to improved cancer treatments.